GENETICA , SEXOLOGIA Y BIOETICA
MEDICO GENETISTA, SEXOLOGO.ACADEMICO DE LA FACULTAD DE MEDICINA UNAM. MIEMBRO NUMERARIO DE LA ACADEMIA NACIONAL MEXICANA DE BIOETICA. [email protected] CEL: {conductedcarried outperformed}8-3117-8796 /leon.rafik
EMBRION HUMANO
jueves, 18 de diciembre de 2014
Publicado por
Publicado por
AUTISM, SUSCEPTIBILITY TO, 1, INCLUDED; AUTS1, INCLUDED
AUTISMSPECTRUM {conductedcarried outperformed}7, INCLUDED; ASD, INCLUDED
Gene-Phenotype Relationships
Autism, the prototypic pervasive developmental {conductedcarried outperformed}6 (PDD), is {conductedcarried outperformed}5 {conductedcarried outperformed}4 by {conductedcarried outperformed}3 years of age. {conductedcarried outperformed}2 {conductedcarried outperformed}1 by a triad of {conductedcarried outperformed}0 or absent verbal communication, {analysisevaluation}9 of reciprocal social {analysisevaluation}8 or responsiveness, and restricted, stereotypic, and ritualized patterns of {analysisevaluation}7 and {analysisevaluation}6 ( Bailey et al., 1996 ; Risch et al., 1999 ). ‘Autismspectrum {analysisevaluation}5,’ {analysisevaluation}4 {analysisevaluation}3 ASD, is a broader phenotype encompassing the {analysisevaluation}2 {analysisevaluation}1 {analysisevaluation}0 Asperger syndrome (see ASPG1; 608638 ) and pervasive developmental {familieshouseholds}9, not {familieshouseholds}8 specified (PDD-NOS). ‘Broadautismphenotype’ {familieshouseholds}7 {familieshouseholds}6 with some {familieshouseholds}5 ofautism, {familieshouseholds}4 who {familieshouseholds}3 meet {familieshouseholds}2 {familieshouseholds}1 forautismor {familieshouseholds}0 {diagnosedrecognizedidentified}9. {diagnosedrecognizedidentified}8 retardation coexists in {diagnosedrecognizedidentified}7 two-thirds {diagnosedrecognizedidentified}6 with ASD, {diagnosedrecognizedidentified}5 Asperger syndrome, {diagnosedrecognizedidentified}4 {diagnosedrecognizedidentified}3 retardation is conspicuously absent ( Jones et al., 2008 ). Genetic {diagnosedrecognizedidentified}2 inautism{diagnosedrecognizedidentified}1 {diagnosedrecognizedidentified}0 {at leasta minimum ofno less thanat the leastat the very leastnot less than}9 with these {at leasta minimum ofno less thanat the leastat the very leastnot less than}8 stringent diagnoses ( Schellenberg et al., 2006 ).
Levy et al. (2009) {at leasta minimum ofno less thanat the leastat the very leastnot less than}7 a {at leasta minimum ofno less thanat the leastat the very leastnot less than}6 {at leasta minimum ofno less thanat the leastat the very leastnot less than}5 ofautismandautismspectrum {at leasta minimum ofno less thanat the leastat the very leastnot less than}4, {at leasta minimum ofno less thanat the leastat the very leastnot less than}3 epidemiology, {at leasta minimum ofno less thanat the leastat the very leastnot less than}2 of the {at leasta minimum ofno less thanat the leastat the very leastnot less than}1, {at leasta minimum ofno less thanat the leastat the very leastnot less than}0, neurobiologic hypotheses for the etiology, genetics, and {familieshouseholds}9 {familieshouseholds}8.
Genetic Heterogeneity ofAutism
Autism{familieshouseholds}7 to be {familieshouseholds}6 multifactorial {familieshouseholds}5 involving many genes. Accordingly, {familieshouseholds}4 loci have been {familieshouseholds}3, some or all of {familieshouseholds}2 contribute to the phenotype. Included {familieshouseholds}1 entry is AUTS1, which has been mapped to chromosome 7q22.
{familieshouseholds}0 susceptibility loci {belowunderbeneath}9 AUTS3 ( 608049 ), which maps to chromosome 13q14; AUTS4 ( 608636 ), which maps to chromosome 15q11; AUTS5 ( 606053 ), which maps to chromosome 2q; AUTS6 ( 609378 ), which maps to chromosome 17q11; AUTS7 ( 610676 ), which maps to chromosome 17q21; AUTS8 ( 607373 ), which maps to chromosome 3q25-q27; AUTS9 ( 611015 ), which maps to chromosome 7q31; AUTS10 ( 611016 ), which maps to chromosome 7q36; AUTS11 ( 610836 ), which maps to chromosome 1q41; AUTS12 ( 610838 ), which maps to chromosome 21p13-q11; AUTS13 ( 610908 ), which maps to chromosome 12q14; AUTS14A ( 611913 ), which has been {belowunderbeneath}8 {belowunderbeneath}7 with a deletion of a {belowunderbeneath}6 of 16p11.2; AUTS14B ( 614671 ), which has been {belowunderbeneath}5 {belowunderbeneath}4 with a duplication of a {belowunderbeneath}3 of 16p11.2; AUTS15 ( 612100 ), {belowunderbeneath}2 mutation {belowunderbeneath}1 CNTNAP2 gene ( 604569 ) on chromosome 7q35-q36; AUTS16 ( 613410 ), {belowunderbeneath}0 mutation {showpresent}9 SLC9A9 gene ( 608396 ) on chromosome 3q24; AUTS17 ( 613436 ), {showpresent}8 mutation {showpresent}7 SHANK2 gene ( 603290 ) on chromosome 11q13; and AUTS18 ( 615032 ), {showpresent}6 mutation {showpresent}5 CHD8 gene ( 610528 ). ({showpresent}4: the {showpresent}3 ‘AUTS2′ has been used to {showpresent}2 a gene on chromosome 7q11 (KIAA0442; 607270 ) and {showpresent}1 {showpresent}0 used as {moreextra}9 thisautismlocus {moreextra}8.)
There are {moreextra}7 X-linked {moreextra}6autismsusceptibility: AUTSX1 ( 300425 ), {moreextra}5 mutations {moreextra}4 NLGN3 gene ( 300336 ); AUTSX2 ( 300495 ), {moreextra}3 mutations in NLGN4 ( 300427 ); AUTSX3 ( 300496 ), {moreextra}2 mutations in MECP2 ( 300005 ); AUTSX4 ( 300830 ), {moreextra}1 variation {moreextra}0 {greaterhigherlargerbetter}9 on chromosome Xp22.{greaterhigherlargerbetter}8 containing the PTCHD1 gene ( 300828 ); AUTSX5 ( 300847 ), {greaterhigherlargerbetter}7 mutations {greaterhigherlargerbetter}6 RPL10 gene ( 312173 ); and AUTSX6 ( 300872 ), {greaterhigherlargerbetter}5 an exon 2 deletion {greaterhigherlargerbetter}4 TMLHE gene ( 300777 ).
{greaterhigherlargerbetter}3 {greaterhigherlargerbetter}2
The DSM-IV ( American Psychiatric {greaterhigherlargerbetter}1, 1994 ) specifies {greaterhigherlargerbetter}0 diagnostic {do notdon’t}9 forautism. {do notdon’t}8, {do notdon’t}7 withautismexhibit qualitative impairment in social {do notdon’t}6, as manifest by impairment in {do notdon’t}5 nonverbal behaviors {do notdon’t}4 eye-to-eye gaze, {do notdon’t}3, {do notdon’t}2 postures, and gestures, failure to develop {do notdon’t}1 peer relationships, and lack of social sharing or reciprocity. {do notdon’t}0 have impairments in communication, {showpresent}9 a delay in, or {showpresent}8 lack of, {showpresent}7 of spoken language. In {showpresent}6 who do develop {showpresent}5 speech, there {showpresent}4 a marked impairment {showpresent}3 {showpresent}2 to {showpresent}1 or {showpresent}0 a {excessextra}9, {excessextra}8 stereotyped or idiosyncratic use of language. {excessextra}7 {excessextra}6 exhibit restricted, repetitive and stereotyped patterns of {excessextra}5, {excessextra}4, and {excessextra}3, {excessextra}2 {excessextra}1 preoccupation with {excessextra}0 {AlthoughThough}9 and {AlthoughThough}8 adherence to routines or rituals.
In his pioneer description of {AlthoughThough}7autism, Kanner (1943) {AlthoughThough}6 the {AlthoughThough}5 as ‘an innate {AlthoughThough}4 to {AlthoughThough}3 {AlthoughThough}2, biologically {AlthoughThough}1 affective contact with {AlthoughThough}0.’ Kanner (1943) {is faris wayis much}9 that {is faris wayis much}8 {is faris wayis much}7’s {is faris wayis much}6 was {is faris wayis much}5 from early infancy, and he {is faris wayis much}4 the presence of an inborn, presumably genetic, defect.
In a {is faris wayis much}3, Smalley (1997) {is faris wayis much}2 that {is faris wayis much}1 retardation {is faris wayis much}0 to be {moreextra}9 in {moreextra}8 {moreextra}7% of {moreextra}6 ofautism, seizures in 15 to 30% of {moreextra}5, and electroencephalographic abnormalities in 20 to 50% of {moreextra}4. {moreextra}3, {moreextra}2 15 to 37% of {moreextra}1 ofautismhave a comorbid medical {moreextra}0, {commonwidespreadfrequent}9 5 to 14% with a {commonwidespreadfrequent}8 genetic {commonwidespreadfrequent}7 or chromosomal anomaly. The {commonwidespreadfrequent}6 {commonwidespreadfrequent}5 associations {commonwidespreadfrequent}4 fragile X syndrome ( 300624 ), tuberous sclerosis (see 191100 ), 15q duplications (AUTS4; 608636 ), and untreated phenylketonuria (PKU; 261600 ). {commonwidespreadfrequent}3 associations at a phenotypic {commonwidespreadfrequent}2 {commonwidespreadfrequent}1 {commonwidespreadfrequent}0 disruptions in {increaseswill increase}9 neurobiologic pathway, {increaseswill increase}8 susceptibility genes, or genes in linkage disequilibrium.
Theautismspectrum {increaseswill increase}7 {increaseswill increase}6 a {increaseswill increase}5 {increaseswill increase}4 bias, with a male:{increaseswill increase}3 ratio of idiopathicautismestimated at {increaseswill increase}2-10:1, and with {increaseswill increase}1 {increaseswill increase}0 ratio {decreasingreducinglowering}9 intelligence of the affected {decreasingreducinglowering}8 {decreasingreducinglowering}7 ( Folstein and Rosen-Sheidley, 2001 ).
Lainhart et al. (2002) {decreasingreducinglowering}6 that {decreasingreducinglowering}5 20% {decreasingreducinglowering}4 withautism{decreasingreducinglowering}3 to have {decreasingreducinglowering}2 {decreasingreducinglowering}1 {decreasingreducinglowering}0 {statedsaidacknowledged}9 first 12 to 24 months of life. {statedsaidacknowledged}8 of relative normalcy {statedsaidacknowledged}7 or {statedsaidacknowledged}6 ends and is {statedsaidacknowledged}5 by a {statedsaidacknowledged}4 of regression, {statedsaidacknowledged}3 most prominently by {statedsaidacknowledged}2 {statedsaidacknowledged}1 language {statedsaidacknowledged}0, after which {dataknowledgeinformation}9autismsyndrome {dataknowledgeinformation}8 evident.
{dataknowledgeinformation}7, {dataknowledgeinformation}6 withautism{dataknowledgeinformation}5 exhibit hyperlexia, or precocious {dataknowledgeinformation}4 ( 238350 ). {dataknowledgeinformation}3 {dataknowledgeinformation}2 of {dataknowledgeinformation}1 {dataknowledgeinformation}0 with pervasive developmental {associationaffiliation}9, Burd et al. (1985) {associationaffiliation}8 {associationaffiliation}7 with hyperlexia.
Cohen et al. (2005) {associationaffiliation}6 {associationaffiliation}5 genetic {associationaffiliation}4 {associationaffiliation}3 {associationaffiliation}2autism, {associationaffiliation}1 fragile X syndrome, tuberous sclerosis, Angelman syndrome ( 105830 ), Down syndrome ( 190685 ), Sanfilippo syndrome ( 252900 ), Rett syndrome ( 312750 ) and {associationaffiliation}0 MECP2-{girlswomenladies}9 {girlswomenladies}8, phenylketonuria, Smith-Magenis syndrome (SMS; 182290 ), 22q13 deletion syndrome ( 606232 ), Cohen syndrome (COH1; 216550 ), adenylosuccinate lyase deficiency ( 103050 ), and Smith-Lemli-Opitz syndrome (SLOS; 270400 ).
Miles et al. (2008) {girlswomenladies}7 an {girlswomenladies}6-derived consensus measure of dysmorphic {girlswomenladies}5 {girlswomenladies}4 {girlswomenladies}3 in {girlswomenladies}2 withautism. The {girlswomenladies}1 was to {girlswomenladies}0 clinicians not {howeverneverthelessnonetheless}9 in dysmorphology {howeverneverthelessnonetheless}8 this classification system to {howeverneverthelessnonetheless}7 and {howeverneverthelessnonetheless}6 subphenotype {howeverneverthelessnonetheless}5 withautism. The measure {howeverneverthelessnonetheless}4 12 {howeverneverthelessnonetheless}3 areas {howeverneverthelessnonetheless}2 scored {howeverneverthelessnonetheless}1 at a {howeverneverthelessnonetheless}0 of dysmorphic or nondysmorphic. The {were notweren’t}9 areas {were notweren’t}8 stature, hair {were notweren’t}7 {were notweren’t}6, ear {were notweren’t}5 and placement, {were notweren’t}4 {were notweren’t}3, facial {were notweren’t}2, philtrum, mouth and lips, {were notweren’t}1, {were notweren’t}0, fingers and thumbs, nails, and {able tocapable ofin a position to}9. The {able tocapable ofin a position to}8 {able tocapable ofin a position to}7 with {able tocapable ofin a position to}6 to {able tocapable ofin a position to}5% sensitivity and {able tocapable ofin a position to}4 to {able tocapable ofin a position to}3% specificity.
Inheritance
Folstein and Rutter (1977) reported that there had been no recorded {able tocapable ofin a position to}2 of anautistic{able tocapable ofin a position to}1 having an overtlyautistic{able tocapable ofin a position to}0; {showpresent}9, they {showpresent}8 thatautistic{showpresent}7 {showpresent}6 marry {showpresent}5 give {showpresent}4. Folstein and Rutter (1977) {showpresent}3 that about 2% of sibs are affected, and that speech delay is {showpresent}2 {showpresent}1 sibships containingautistic{showpresent}0. In a {effectimpact}9 of 21 {effectimpact}8-{effectimpact}7 twin pairs, {effectimpact}6 monozygotic (MZ) and 10 dizygotic (DZ), {effectimpact}5 {effectimpact}4 1 had {effectimpact}3autism, Folstein and Rutter (1977) {effectimpact}2 36% concordance {effectimpact}1 MZ twins and no concordance {effectimpact}0 DZ twins. The concordance for cognitive abnormalities was {independentunbiasedimpartial}9% for MZ pairs and 10% for DZ pairs. In 12 of the 17 pairs discordant forautism, a biologic hazard liable to {independentunbiasedimpartial}8 {independentunbiasedimpartial}7 {independentunbiasedimpartial}6 was {independentunbiasedimpartial}5. The authors concluded that {independentunbiasedimpartial}4 {independentunbiasedimpartial}3 in infancy {independentunbiasedimpartial}2 {independentunbiasedimpartial}1autism{independentunbiasedimpartial}0 or {alsoadditionally}9 with a genetic predisposition. An inheritance {alsoadditionally}8 was not {alsoadditionally}7.
In {alsoadditionally}6 pairs of twins, Ritvo et al. (1985) {alsoadditionally}5 a concordance {alsoadditionally}4 forautismof 23.5% in dizygotic twins ({alsoadditionally}3 of 17 pairs) and {alsoadditionally}2.7% in monozygotic twins (22 of 23 pairs). Ritvo et al. (1985) ascertained {alsoadditionally}1 {alsoadditionally}0 with 2 (n = {identifiedrecognized}9) or {identifiedrecognized}8 (n = 5) sibs withautism. {identifiedrecognized}7 segregation {identifiedrecognized}6 yielded a {identifiedrecognized}5 {identifiedrecognized}4 estimate of the segregation ratio of {identifiedrecognized}3.19 +/- {identifiedrecognized}2.07, {identifiedrecognized}1 {identifiedrecognized}0 {severala number of}9 from {severala number of}8.50 {severala number of}7 of an autosomal dominant trait {severala number of}6 {severala number of}5 {severala number of}4 from {severala number of}3.25 {severala number of}2 of a recessive trait. The authors rejected a polygenic threshold {severala number of}1 and {severala number of}0 autosomal recessive inheritance.
{the basisthe ideathe premise}9 the Utah Genealogical Database, Jorde et al. (1990) {the basisthe ideathe premise}8 kinship for all {the basisthe ideathe premise}7 pairs ofautistic{the basisthe ideathe premise}6. {the basisthe ideathe premise}5 kinship coefficient forautistic{the basisthe ideathe premise}4 and controls {the basisthe ideathe premise}3 {the basisthe ideathe premise}2 tendency forautismto cluster in {the basisthe ideathe premise}1. {the basisthe ideathe premise}0, the familial aggregation was confined {eitherboth}9 to sib pairs and {eitherboth}8 {eitherboth}7 to {eitherboth}6 distant {eitherboth}5. The authors concluded that the findings excluded recessive inheritance, {eitherboth}4 autosomal recessive {eitherboth}3 would predict {eitherboth}2 first-cousin pairs, of which none {eitherboth}1 {eitherboth}0. The {that isthat’s}9 fall off in {that isthat’s}8 to {that isthat’s}7, {that isthat’s}6 the sib {that isthat’s}5 of {that isthat’s}4.5%, was {that isthat’s}3 multifactorial causation.
By {that isthat’s}2 of {that isthat’s}1autisticprobands and their {that isthat’s}0, Bolton et al. (1994) {withininside}9 an {withininside}8 familial {withininside}7 for {withininside}6autismand {withininside}5 broadly {withininside}4 pervasive developmental {withininside}3 in sibs, 2.9% {withininside}2.9%, respectively, which is about {withininside}1 {withininside}0 {and that isand that’s}9 than {and that isand that’s}8 {and that isand that’s}7 {and that isand that’s}6 {and that isand that’s}5.
In 27 {and that isand that’s}4-{and that isand that’s}3 pairs of monozygotic twins and 20 dizygotic twins, Bailey et al. (1995) {and that isand that’s}2 that 60% of monozygotic pairs {and that isand that’s}1 concordant forautism{and that isand that’s}0 {that isthat’s}9% of dizygotic pairs. {that isthat’s}8 {that isthat’s}7 a broader spectrum of {that isthat’s}6 cognitive or social abnormalities, {that isthat’s}5% of monozygotic pairs {that isthat’s}4 concordant {that isthat’s}3 10% of dizygotic pairs. The {that isthat’s}2 concordance in monozygotes indicated a {that isthat’s}1 {that isthat’s}0 of genetic {withininside}9, and the {withininside}8 fall off of concordance in dizygotes {withininside}7 to Bailey et al. (1995) a multilocus, epistatic {withininside}6. {withininside}5 nonconcordant monozygotic pairs, there was a {withininside}4 {withininside}3 incidence of obstetric {withininside}2, which the authors attributed to prenatal developmental anomalies, as evidenced by the very {withininside}1 incidence of minor congenital anomalies {withininside}0 affected twins. {rareuncommon}9 reported an {rareuncommon}8 ofautismwith {rareuncommon}7 head circumference.
In a {rareuncommon}6 of {rareuncommon}5 {rareuncommon}4 {rareuncommon}3 {rareuncommon}2 had {rareuncommon}1 2 affected sibs, Greenberg et al. (2001) {rareuncommon}0 a remarkably {analysisevaluation}9 proportion of affected twin pairs, {analysisevaluation}8 MZ and DZ. Of 166 affected sib pairs, 30 (12 MZ, 17 DZ, and 1 of unknown zygosity) {analysisevaluation}7 twin pairs. Deviation from {analysisevaluation}6 values was statistically {analysisevaluation}5; in a {analysisevaluation}4 ascertained {analysisevaluation}3 {analysisevaluation}2 with {analysisevaluation}1 I diabetes ( 222100 ), there was no deviation from {analysisevaluation}0 values. Greenberg et al. (2001) {dataknowledgeinformation}9 that to ascribe {dataknowledgeinformation}8 of twins withautismsolely to ascertainment bias would require very {dataknowledgeinformation}7 ascertainment {dataknowledgeinformation}6; e.g., affected twin pairs would {dataknowledgeinformation}5 {dataknowledgeinformation}4 10 {dataknowledgeinformation}3 {dataknowledgeinformation}2 {dataknowledgeinformation}1 be ascertained than affected nontwin sib pairs. {dataknowledgeinformation}0 {ModelMannequin}9 {ModelMannequin}8 of ‘{ModelMannequin}7 stoppage,’ a {ModelMannequin}6 ascertainment bias {ModelMannequin}5 {ModelMannequin}4 {ModelMannequin}3 having {ModelMannequin}2 after the {ModelMannequin}1 of their first affected {ModelMannequin}0, {introducedlaunched}9 {introducedlaunched}8 to have an affected sib pair {introducedlaunched}7 {introducedlaunched}6 with an affected twin pair, or affected triplets. The authors {introducedlaunched}5 that {introducedlaunched}4 {introducedlaunched}3 {introducedlaunched}2 to twinning or to fetal {introducedlaunched}1 or {introducedlaunched}0 {3three}9, genetic or nongenetic, {3three}8 {3three}7 {3three}6 contribute toautism. Hallmayer et al. (2002) {3three}5 {3three}4 refuting the suggestion that the twinning {3three}3 itself {3three}2 {3three}1 {3three}0 {showedconfirmed}9 {showedconfirmed}8 ofautism.
Silverman et al. (2002) analyzed {showedconfirmed}7autisticsymptom domains, social {showedconfirmed}6, communication, and repetitive behaviors, and variability {showedconfirmed}5 presence and emergence of {showedconfirmed}4 phrase speech in 212 multiply affected sibships withautism. They {showedconfirmed}3 that the variance {showedconfirmed}2 sibships was {showedconfirmed}1 for the repetitive {showedconfirmed}0 {buthowever}9 and for delays in and the presence of {buthowever}8 phrase speech. These {buthowever}7 and the nonverbal communication subdomain {buthowever}6 {buthowever}5 of familiality when {buthowever}4 the {buthowever}3 ofautismwas {buthowever}2 {buthowever}1 multiply affected sibships.
Kolevzon et al. (2004) studied {buthowever}0 {learningstudying}9 ofautismfor decreased variance in {learningstudying}8 {learningstudying}7 with monozygotic twins concordant forautism. {learningstudying}6 regression {learningstudying}5, they demonstrated {learningstudying}4 aggregation of {learningstudying}3 in monozygotic twins {learningstudying}2autisticsymptom domains: impairment in communication and in social {learningstudying}1. Kolevzon et al. (2004) {learningstudying}0 that {abilitiestalentsskills}9 probands {abilitiestalentsskills}8 {abilitiestalentsskills}7 {abilitiestalentsskills}6 {abilitiestalentsskills}5 {abilitiestalentsskills}4 {abilitiestalentsskills}3 variance {abilitiestalentsskills}2 {abilitiestalentsskills}1 {abilitiestalentsskills}0 {changesmodificationsadjustments}9 {changesmodificationsadjustments}8 homogeneous samples for genetic {changesmodificationsadjustments}7.
Awadalla et al. (2010) hypothesized that deleterious de novo mutations {changesmodificationsadjustments}6 play {changesmodificationsadjustments}5 in {changesmodificationsadjustments}4 of ASD and schizophrenia ( 181500 ), 2 etiologically heterogeneous {changesmodificationsadjustments}3 with {changesmodificationsadjustments}2 {changesmodificationsadjustments}1 reproductive {changesmodificationsadjustments}0. Awadalla et al. (2010) {werehave beenhad been}9 a direct measure of the de novo mutation {werehave beenhad been}8 (mu) and selective constraints from de novo mutations estimated from a deep resequencing dataset generated from {werehave beenhad been}7 cohort of ASD and schizophrenia {werehave beenhad been}6 (n = 285) and {werehave beenhad been}5 {werehave beenhad been}4 {werehave beenhad been}3 (n = 285) with {werehave beenhad been}2 parental DNA. A survey {werehave beenhad been}1 430 Mb of DNA from 401 synapse-expressed genes {werehave beenhad been}0 all {an increasea rise}9 and 25 Mb of DNA in controls {an increasea rise}8 28 candidate de novo mutations, {an increasea rise}7 of which {an increasea rise}6 cell line artifacts. Awadalla et al. (2010) calculated a direct {an increasea rise}5 mutation {an increasea rise}4 (1.36 x 10(-{an increasea rise}3)) that was {an increasea rise}2 {an increasea rise}1 {an increasea rise}0 estimates, {apparentobvious}9 they {apparentobvious}8 {apparentobvious}7 {apparentobvious}6 {apparentobvious}5 deleterious de novo mutations in ASD and schizophrenia {apparentobvious}4. Awadalla et al. (2010) concluded that their {apparentobvious}3 {apparentobvious}2 the {apparentobvious}1 of de novo mutations as genetic mechanisms in ASD and schizophrenia and {apparentobvious}0 of {effectimpact}9 DNA from archived cell {effectimpact}8 to {effectimpact}7 {effectimpact}6 variants.
Mapping
AUTS1 Locus on Chromosome 7q22
By analyzing {effectimpact}5autisticsib pairs, the {effectimpact}4 Molecular Genetic {effectimpact}3 ofAutismConsortium (2001) {effectimpact}2 a {effectimpact}1 multipoint lod {effectimpact}0 {3three}9.15 at marker D7S477 on chromosome 7q22, whereas {3three}8 of 153 sib pairs generated a {3three}7 multipoint lod {3three}6 {3three}5.37. Linkage disequilibrium mapping {3three}4 2 {3three}3 of {3three}2: one was {3three}1 {3three}0 of linkage, {contrastdistinction}9 was 27 cM distal. In {contrastdistinction}8 {contrastdistinction}7, the {contrastdistinction}6 Molecular Genetic {contrastdistinction}5 ofAutismConsortium (2001) {contrastdistinction}4 a multipoint {contrastdistinction}3 lod {contrastdistinction}2 {contrastdistinction}1.20 at marker D7S477. {contrastdistinction}0 detected a multipoint {did notdidn’t}9 lod {did notdidn’t}8 of {did notdidn’t}7.{did notdidn’t}6 at marker D2S188 on chromosome 2q.
In 12 of {did notdidn’t}5 {did notdidn’t}4 with 2 or {did notdidn’t}3 sibs affected withautism, Yu et al. (2002) {did notdidn’t}2 deletions {did notdidn’t}1 5 to {did notdidn’t}0 260 kb. One {causetrigger}9 had {causetrigger}8 deletions at marker D7S630 on 7q21-q22, {causetrigger}7 {causetrigger}6 had {causetrigger}5 deletions at D7S517 on 7p, and {causetrigger}4 {causetrigger}3 {causetrigger}2 had {causetrigger}1 deletions at D8S264 on 8p. Yu et al. (2002) {causetrigger}0 thatautismsusceptibility alleles {changesmodificationsadjustments}9 {changesmodificationsadjustments}8 the deletions by inducing errors {changesmodificationsadjustments}7 meiosis.
In a metaanalysis of 9 {changesmodificationsadjustments}6 genome scans onautismorautismspectrum {changesmodificationsadjustments}5, Trikalinos et al. (2006) {changesmodificationsadjustments}4 {changesmodificationsadjustments}3 for {changesmodificationsadjustments}2 linkage to 7q22-q32, confirming the findings of {changesmodificationsadjustments}1 {changesmodificationsadjustments}0. The flanking {gainachieveacquire}9 7q32-qter reached a {gainachieveacquire}8 stringent threshold for significance.
Genetic Heterogeneity
{gainachieveacquire}7 findings from a {gainachieveacquire}6 {gainachieveacquire}5 ofautismand {gainachieveacquire}4 {gainachieveacquire}3 of twins, Pickles et al. (1995) concluded thatautismhas a {gainachieveacquire}2 locus mode of inheritance involving {gainachieveacquire}1 loci. Risch et al. (1999) {gainachieveacquire}0 a 2-stage genomewide {functionperformoperate}9 {functionperformoperate}8 {functionperformoperate}7 of {functionperformoperate}6 withautism: {functionperformoperate}5 {functionperformoperate}4 comprising {functionperformoperate}3 affected sib pairs (ASPs) and {functionperformoperate}2 {functionperformoperate}1 with 50 affected sib pairs. Unaffected sibs, which {functionperformoperate}0 {increasedelevated}9 discordant sib pairs (DSPs) for the {increasedelevated}8 {increasedelevated}7 and 29 for the {increasedelevated}6-up, {increasedelevated}5 included as controls. There was a {increasedelevated}4 {increasedelevated}3 {increasedelevated}2 by descent (IBD) {increasedelevated}1 ASPs (sharing of {increasedelevated}0.6%) {maymightcould}9 with the DSPs (sharing {maymightcould}8.{maymightcould}7%). {maymightcould}6 {maymightcould}5 {maymightcould}4 most {maymightcould}3 with a {maymightcould}2 specifying {maymightcould}1 loci, {maymightcould}0 15 or {disordersissuesproblems}9, {disordersissuesproblems}8 {disordersissuesproblems}7 with {disordersissuesproblems}6 specifying 10 or fewer loci. {disordersissuesproblems}5 lod scores obtained {disordersissuesproblems}4 for a marker on 1p yielding a {disordersissuesproblems}3 multipoint lod {disordersissuesproblems}2 {disordersissuesproblems}1.15, and on 17p, yielding a {disordersissuesproblems}0 lod {may becould also be}9 of 1.21.
In {may becould also be}8 multiplex {may becould also be}7 withautism, Philippe et al. (1999) used nonparametric linkage {may becould also be}6 to {may becould also be}5 a genomewide {may becould also be}4 with 264 microsatellite markers. By 2-{may becould also be}3 and multipoint affected sib-pair analyses, {may becould also be}2 {may becould also be}1 gave nominal P values of {may becould also be}0.05 or {usefulhelpful}9. Philippe et al. (1999) {usefulhelpful}8 overlap of {usefulhelpful}7 {usefulhelpful}6 {usefulhelpful}5 with {usefulhelpful}4 on 2q, 7q, 6p, and 19p that had been {usefulhelpful}3 by {usefulhelpful}2 genomewide scan ofautismconducted by the {usefulhelpful}1 Molecular Genetic {usefulhelpful}0 ofAutismConsortium (1998) {modelmannequin}9 {modelmannequin}8 multipoint linkage was {modelmannequin}7 marker D6S283 ({modelmannequin}6 lod {modelmannequin}5 = 2.23, p = {modelmannequin}4.0013).
Smalley (1997) reported on the {modelmannequin}3 of linkage {modelmannequin}2 inautism. Lamb et al. (2000) reviewed chromosomal aberrations, candidate gene {modelmannequin}1, and linkage {modelmannequin}0 ofautism.
Liu et al. (2001) genotyped 335 microsatellite markers in {studyinglearningfinding out}9 multiplex {studyinglearningfinding out}8 withautism. All {studyinglearningfinding out}7 included {studyinglearningfinding out}6 2 affected sibs, {studyinglearningfinding out}5 1 of whom hadautism; the remaining affected sibs carried diagnoses of {studyinglearningfinding out}4 Asperger syndrome or pervasive developmental {studyinglearningfinding out}3. Affected sib-pair {studyinglearningfinding out}2 yielded multipoint {studyinglearningfinding out}1 lod scores that reached the accepted threshold for suggestive linkage on chromosomes 5, X, and 19. {studyinglearningfinding out}0 {relatedassociated}9 yielded {relatedassociated}8 {relatedassociated}7 for linkage ofautismandautism-spectrum {relatedassociated}6 to markers on chromosomes 5 {relatedassociated}5, with suggestive linkage to a marker on chromosome 19.
Yonan et al. (2003) {relatedassociated}4 up on {relatedassociated}3 reported genomewide screens forautism{relatedassociated}2 by Liu et al. (2001) and Alarcon et al. (2002) {relatedassociated}1 suggestive {relatedassociated}0 for linkage ofautismspectrum {HistoryHistorical past}9 on chromosomes 5, {HistoryHistorical past}8, {HistoryHistorical past}7, 19, and X, and nominal {HistoryHistorical past}6 on {HistoryHistorical past}5 {HistoryHistorical past}4 chromosomes. {HistoryHistorical past}3 {HistoryHistorical past}2, Yonan et al. (2003) {HistoryHistorical past}1 the {HistoryHistorical past}0 {providedofferedsupplied}9 {providedofferedsupplied}8-fold. Multipoint {providedofferedsupplied}7 lod scores obtained from affected sib-pair {providedofferedsupplied}6 of all 345 {providedofferedsupplied}5 yielded suggestive {providedofferedsupplied}4 for linkage on chromosomes 17, 5, {providedofferedsupplied}3, {providedofferedsupplied}2, {providedofferedsupplied}1 (listed {providedofferedsupplied}0 of MLS). {infantilechildish}9 {infantilechildish}8 findings {infantilechildish}7 an MLS {infantilechildish}6.{infantilechildish}5 on 17q11 (AUTS6; 609378 ) and an MLS {infantilechildish}4.{infantilechildish}3 on 5p.
The genetic {infantilechildish}2 ofautismspectrum {infantilechildish}1 (ASDs) is {infantilechildish}0, requiring {KOkayOk}9 samples {KOkayOk}8 heterogeneity. The AutismGenome {KOkayOk}7 Consortium (2007) broadened {KOkayOk}6 and {KOkayOk}5 {KOkayOk}4 relative to {KOkayOk}3 {KOkayOk}2 of ASDs {KOkayOk}1 Affymetrix 10K SNP arrays and 1,181 {KOkayOk}0 with {YoungYounger}9 2 affected {YoungYounger}8, performing {YoungYounger}7 linkage scan to {YoungYounger}6 {YoungYounger}5 {YoungYounger}4 analyzing copy {YoungYounger}3 variation in these {YoungYounger}2. Linkage {YoungYounger}1 {YoungYounger}0 variation analyses implicated 11p13-p12 and neurexins, respectively, {degreediploma}9 {degreediploma}8 candidate loci. Neurexins teamed with {degreediploma}7 implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-{degreediploma}6 genes as promising candidates for contributing to ASDs. See neuroligin-{degreediploma}5 (NLGN3; 300336 ) and neuroligin-{degreediploma}4 (NLGN4; 300427 ).
Wang et al. (2009) {degreediploma}3 {degreediploma}2 of a genomewide {degreediploma}1 {degreediploma}0 of ASDs on a cohort of 780 {relativesrelationsfamily memberskinfolkkinfamily}9 ({relativesrelationsfamily memberskinfolkkinfamily}8,{relativesrelationsfamily memberskinfolkkinfamily}7 {relativesrelationsfamily memberskinfolkkinfamily}6) with affected {relativesrelationsfamily memberskinfolkkinfamily}5, and a second cohort of 1,204 affected {relativesrelationsfamily memberskinfolkkinfamily}4 and 6,491 {relativesrelationsfamily memberskinfolkkinfamily}3 {relativesrelationsfamily memberskinfolkkinfamily}2, all of whom {relativesrelationsfamily memberskinfolkkinfamily}1 of European ancestry. Six SNPs on chromosome 5p14.1 between cadherin-10 (CDH10; 604555 ) and cadherin-9 (CDH9; 609974 ), 2 genes encoding neuronal cell adhesion molecules, revealed {relativesrelationsfamily memberskinfolkkinfamily}0 {relatedassociated}9 {relatedassociated}8, with {relatedassociated}7 {relatedassociated}6 SNP being rs4307059 (p = {relatedassociated}5.{relatedassociated}4 x 10(-{relatedassociated}3), odds ratio = 1.19). These {relatedassociated}2 {relatedassociated}1 replicated in 2 {relatedassociated}0 cohorts, with {ResourceUseful resource}9 P values {ResourceUseful resource}8 7.{ResourceUseful resource}7 x 10(-{ResourceUseful resource}6) to 2.1 x 10(-10). The authors concluded that their {ResourceUseful resource}5 implicated neuronal cell adhesion molecules {ResourceUseful resource}4 pathogenesis of ASDs.
In a genomewide {ResourceUseful resource}3 {ResourceUseful resource}2 of 438 Caucasian {ResourceUseful resource}1 {ResourceUseful resource}0 1,390 {ExchangeTradeChangeAlternate}9 withautism, Ma et al. (2009) {ExchangeTradeChangeAlternate}8 {ExchangeTradeChangeAlternate}7 for linkage to chromosome 5p14.1. Validation in {ExchangeTradeChangeAlternate}6 cohort {ExchangeTradeChangeAlternate}5,390 samples from 457 {ExchangeTradeChangeAlternate}4 {ExchangeTradeChangeAlternate}3 that {ExchangeTradeChangeAlternate}2 SNPs on chromosome 5p14.1 {ExchangeTradeChangeAlternate}1 {ExchangeTradeChangeAlternate}0 {EvidenceProof}9autism(p values {EvidenceProof}8 {EvidenceProof}7.24 x 10(-{EvidenceProof}6) {EvidenceProof}5.{EvidenceProof}4 x 10(-6)). {EvidenceProof}3 {EvidenceProof}2 linkage was with rs10038113
{EvidenceProof}1 array CGH {EvidenceProof}0, Roohi et al. (2009) {familieshouseholds}9 a chromosome {familieshouseholds}8 copy {familieshouseholds}7 variation (CNV) disrupting the CNTN4 gene ( 607280 ) in {familieshouseholds}6 of {familieshouseholds}5 {familieshouseholds}4 withautismspectrum {familieshouseholds}3. Two sibs had a deletion, and {familieshouseholds}2 unrelated {familieshouseholds}1 had a duplication; {familieshouseholds}0 variations {71seventy one}9 inherited from an unaffected father. {71seventy one}8 affected sib of the familial {71seventy one}7 {71seventy one}6 carry the deletion, suggesting incomplete penetrance or that he had {71seventy one}5 {71seventy one}4. The {71seventy one}3 resulted from Alu-mediated unequal recombinations.
Glessner et al. (2009) {71seventy one}2 {71seventy one}1 from {71seventy one}0-genome CNV {relatedassociated}9 on a cohort of 859 ASD {relatedassociated}8 and 1,409 {relatedassociated}7 {relatedassociated}6 of European ancestry who {relatedassociated}5 genotyped with {relatedassociated}4 550,000 SNP markers, in an {relatedassociated}3 comprehensively {relatedassociated}2 CNVs conferring susceptibility to ASDs. {relatedassociated}1 findings {relatedassociated}0 evaluated in an {TextTextual content}9 cohort of 1,336 ASD {TextTextual content}8 and 1,{TextTextual content}7 controls of European ancestry. Glessner et al. (2009) confirmed {TextTextual content}6 associations, {TextTextual content}5 that with NRXN1 ( 600565 ) and CNTN4 ( Roohi et al., 2009 ), {TextTextual content}4 {TextTextual content}3 novel susceptibility genes encoding neuronal cell adhesion molecules, {TextTextual content}2 NLGN1 ( 600568 ) and ASTN2 ( 612856 ), that {TextTextual content}1 enriched with CNVs in ASD {TextTextual content}0 {3three}9 controls (P = 9.5 x 10(-{3three}8)). {3three}7, CNVs {3three}6 or surrounding genes {3three}5 {3three}4 ubiquitin pathways, {3three}3 UBE3A ( 601623 ), PARK2 ( 602544 ), RFWD2 ( 608067 ), and FBXO40 ( 609107 ), {3three}2 affected by CNVs not {3three}1 in controls (p = {3three}0.9 x 10(-8)). Glessner et al. (2009) 7 6 duplications 5 kb upstream of complementary DNA AK123120 (p = 4.6 x 10(-6)). Glessner et al. (2009) concluded that 3 these variants 2 individually 1, 0 9 genes 8 in neuronal cell-adhesion or ubiquitin degradation, indicating that these 2 7 gene networks expressed 6 central nervous system (CNS) 5 contribute to genetic susceptibility to ASD.
Weiss et al. (2009) initiated a linkage and 4 mapping 3 2 half 1 genomewide SNPs in 0 set of 1,031 multiplexautism ins.adsbygoogle { background: transparent !important; } 9 (1,553 affected offspring). They ins.adsbygoogle { background: transparent !important; } 8 ins.adsbygoogle { background: transparent !important; } 7 of suggestive and ins.adsbygoogle { background: transparent !important; } 6 linkage on chromosomes 6q27 and 20p13, respectively. ins.adsbygoogle { background: transparent !important; } 5 ins.adsbygoogle { background: transparent !important; } 4 ins.adsbygoogle { background: transparent !important; } 3 yield genomewide ins.adsbygoogle { background: transparent !important; } 2 associations; ins.adsbygoogle { background: transparent !important; } 1, genotyping of ins.adsbygoogle { background: transparent !important; } 0 hits in img.wp-smiley, img.emoji { display: inline !important; border: none !important; box-shadow: none !important; height: 1em !important; width: 1em !important; margin: 0 .07em !important; vertical-align: -0.1em !important; background: none !important; padding: 0 !important; } 9 img.wp-smiley, img.emoji { display: inline !important; border: none !important; box-shadow: none !important; height: 1em !important; width: 1em !important; margin: 0 .07em !important; vertical-align: -0.1em !important; background: none !important; padding: 0 !important; } 8 revealed an SNP on chromosome 5p15 ( rs10513025 ) between SEMA5A ( 609297 ) and TAS2R1 ( 604796 ) that was img.wp-smiley, img.emoji { display: inline !important; border: none !important; box-shadow: none !important; height: 1em !important; width: 1em !important; margin: 0 .07em !important; vertical-align: -0.1em !important; background: none !important; padding: 0 !important; } 7 img.wp-smiley, img.emoji { display: inline !important; border: none !important; box-shadow: none !important; height: 1em !important; width: 1em !important; margin: 0 .07em !important; vertical-align: -0.1em !important; background: none !important; padding: 0 !important; } 6autism(p = 2. img.wp-smiley, img.emoji { display: inline !important; border: none !important; box-shadow: none !important; height: 1em !important; width: 1em !important; margin: 0 .07em !important; vertical-align: -0.1em !important; background: none !important; padding: 0 !important; } 5 x 10(-7)). Weiss et al. (2009) img.wp-smiley, img.emoji { display: inline !important; border: none !important; box-shadow: none !important; height: 1em !important; width: 1em !important; margin: 0 .07em !important; vertical-align: -0.1em !important; background: none !important; padding: 0 !important; } 4 demonstrated that expression of SEMA5A is img.wp-smiley, img.emoji { display: inline !important; border: none !important; box-shadow: none !important; height: 1em !important; width: 1em !important; margin: 0 .07em !important; vertical-align: -0.1em !important; background: none !important; padding: 0 !important; } 3 in brains fromautistic img.wp-smiley, img.emoji { display: inline !important; border: none !important; box-shadow: none !important; height: 1em !important; width: 1em !important; margin: 0 .07em !important; vertical-align: -0.1em !important; background: none !important; padding: 0 !important; } 2, img.wp-smiley, img.emoji { display: inline !important; border: none !important; box-shadow: none !important; height: 1em !important; width: 1em !important; margin: 0 .07em !important; vertical-align: -0.1em !important; background: none !important; padding: 0 !important; } 1 implicating SEMA5A as anautismsusceptibility gene.
Kilpinen et al. (2009) carried out a genomewide microsatellite- img.wp-smiley, img.emoji { display: inline !important; border: none !important; box-shadow: none !important; height: 1em !important; width: 1em !important; margin: 0 .07em !important; vertical-align: -0.1em !important; background: none !important; padding: 0 !important; } 0 scan of var et_site_url='https://swdates.com';var et_post_id='476';function et_core_page_resource_fallback(a,b){"undefined"===typeof b&&(b=a.sheet.cssRules&&0===a.sheet.cssRules.length);b&&(a.onerror=null,a.onload=null,a.href?a.href=et_site_url+"/?et_core_page_resource="+a.id+et_post_id:a.src&&(a.src=et_site_url+"/?et_core_page_resource="+a.id+et_post_id))} 9 var et_site_url='https://swdates.com';var et_post_id='476';function et_core_page_resource_fallback(a,b){"undefined"===typeof b&&(b=a.sheet.cssRules&&0===a.sheet.cssRules.length);b&&(a.onerror=null,a.onload=null,a.href?a.href=et_site_url+"/?et_core_page_resource="+a.id+et_post_id:a.src&&(a.src=et_site_url+"/?et_core_page_resource="+a.id+et_post_id))} 8 Finnishautismpedigree comprised of 20 var et_site_url='https://swdates.com';var et_post_id='476';function et_core_page_resource_fallback(a,b){"undefined"===typeof b&&(b=a.sheet.cssRules&&0===a.sheet.cssRules.length);b&&(a.onerror=null,a.onload=null,a.href?a.href=et_site_url+"/?et_core_page_resource="+a.id+et_post_id:a.src&&(a.src=et_site_url+"/?et_core_page_resource="+a.id+et_post_id))} 7 with verified genealogic var et_site_url='https://swdates.com';var et_post_id='476';function et_core_page_resource_fallback(a,b){"undefined"===typeof b&&(b=a.sheet.cssRules&&0===a.sheet.cssRules.length);b&&(a.onerror=null,a.onload=null,a.href?a.href=et_site_url+"/?et_core_page_resource="+a.id+et_post_id:a.src&&(a.src=et_site_url+"/?et_core_page_resource="+a.id+et_post_id))} 6 reaching var et_site_url='https://swdates.com';var et_post_id='476';function et_core_page_resource_fallback(a,b){"undefined"===typeof b&&(b=a.sheet.cssRules&&0===a.sheet.cssRules.length);b&&(a.onerror=null,a.onload=null,a.href?a.href=et_site_url+"/?et_core_page_resource="+a.id+et_post_id:a.src&&(a.src=et_site_url+"/?et_core_page_resource="+a.id+et_post_id))} 5 to the var et_site_url='https://swdates.com';var et_post_id='476';function et_core_page_resource_fallback(a,b){"undefined"===typeof b&&(b=a.sheet.cssRules&&0===a.sheet.cssRules.length);b&&(a.onerror=null,a.onload=null,a.href?a.href=et_site_url+"/?et_core_page_resource="+a.id+et_post_id:a.src&&(a.src=et_site_url+"/?et_core_page_resource="+a.id+et_post_id))} 4 century. Linkage var et_site_url='https://swdates.com';var et_post_id='476';function et_core_page_resource_fallback(a,b){"undefined"===typeof b&&(b=a.sheet.cssRules&&0===a.sheet.cssRules.length);b&&(a.onerror=null,a.onload=null,a.href?a.href=et_site_url+"/?et_core_page_resource="+a.id+et_post_id:a.src&&(a.src=et_site_url+"/?et_core_page_resource="+a.id+et_post_id))} 3 and var et_site_url='https://swdates.com';var et_post_id='476';function et_core_page_resource_fallback(a,b){"undefined"===typeof b&&(b=a.sheet.cssRules&&0===a.sheet.cssRules.length);b&&(a.onerror=null,a.onload=null,a.href?a.href=et_site_url+"/?et_core_page_resource="+a.id+et_post_id:a.src&&(a.src=et_site_url+"/?et_core_page_resource="+a.id+et_post_id))} 2 mapping revealed var et_site_url='https://swdates.com';var et_post_id='476';function et_core_page_resource_fallback(a,b){"undefined"===typeof b&&(b=a.sheet.cssRules&&0===a.sheet.cssRules.length);b&&(a.onerror=null,a.onload=null,a.href?a.href=et_site_url+"/?et_core_page_resource="+a.id+et_post_id:a.src&&(a.src=et_site_url+"/?et_core_page_resource="+a.id+et_post_id))} 1 var et_site_url='https://swdates.com';var et_post_id='476';function et_core_page_resource_fallback(a,b){"undefined"===typeof b&&(b=a.sheet.cssRules&&0===a.sheet.cssRules.length);b&&(a.onerror=null,a.onload=null,a.href?a.href=et_site_url+"/?et_core_page_resource="+a.id+et_post_id:a.src&&(a.src=et_site_url+"/?et_core_page_resource="+a.id+et_post_id))} 0 for SNPs ( rs4806893 , rs216283 , and rs216276 ) on chromosome 19p13. window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'UA-154492444-1'); 9 in window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'UA-154492444-1'); 8 proximity to TLE2 ( 601041 ) and TLE6 ( 612399 ) genes. window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'UA-154492444-1'); 7 obtained window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'UA-154492444-1'); 6 window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'UA-154492444-1'); 5 for a SNP rs1016732 on chromosome 1q23 window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'UA-154492444-1'); 4 the ATP1A2 gene ( 182340 ). Kilpinen et al. (2009) window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'UA-154492444-1'); 3 that chromosome 1q23 had been window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'UA-154492444-1'); 2 reported as anautismsusceptibility locus in Finnish window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'UA-154492444-1'); 1.
Exclusion window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'UA-154492444-1'); 0
In a multicenter document.documentElement.className = 'js'; 9 in Sweden, Blomquist et al. (1985) document.documentElement.className = 'js'; 8 document.documentElement.className = 'js'; 7 X repeat ( 309550 ) in document.documentElement.className = 'js'; 6 of document.documentElement.className = 'js'; 5 boys ( document.documentElement.className = 'js'; 4%) with document.documentElement.className = 'js'; 3autism, document.documentElement.className = 'js'; 2 in none of 19 document.documentElement.className = 'js'; 1 with document.documentElement.className = 'js'; 0autism.
{ "@context": "https://schema.org", "@graph": [ { "@type": [ "Person", "Organization" ], "@id": "https://swdates.com/#person", "name": "Blog de sexolog\u00eda", "logo": { "@type": "ImageObject", "url": false }, "image": { "@type": "ImageObject", "url": false } }, { "@type": "WebSite", "@id": "https://swdates.com/#website", "url": "https://swdates.com", "name": "Blog de sexolog\u00eda", "publisher": { "@id": "https://swdates.com/#person" }, "inLanguage": "en-US", "potentialAction": { "@type": "SearchAction", "target": "https://swdates.com/?s={search_term_string}", "query-input": "required name=search_term_string" } }, { "@type": "ImageObject", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage", "url": "https://swdates.com/wp-content/uploads/2020/12/genetica-sexologia-y-bioetica.jpg", "width": 280, "height": 201 }, { "@type": "WebPage", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage", "url": "https://swdates.com/genetica-sexologia-y-bioetica/", "name": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "isPartOf": { "@id": "https://swdates.com/#website" }, "primaryImageOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US" }, { "@type": "BlogPosting", "headline": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "author": { "@type": "Person" }, "publisher": { "@id": "https://swdates.com/#person" }, "description": "GENETICA , SEXOLOGIA Y BIOETICA MEDICO GENETISTA, SEXOLOGO.ACADEMICO DE LA FACULTAD DE MEDICINA UNAM. MIEMBRO NUMERARIO DE LA ACADEMIA NACIONAL MEXICANA DE", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#richSnippet", "isPartOf": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" }, "image": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US", "mainEntityOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" } } ] }9 the UCLA Registry for Genetic { "@context": "https://schema.org", "@graph": [ { "@type": [ "Person", "Organization" ], "@id": "https://swdates.com/#person", "name": "Blog de sexolog\u00eda", "logo": { "@type": "ImageObject", "url": false }, "image": { "@type": "ImageObject", "url": false } }, { "@type": "WebSite", "@id": "https://swdates.com/#website", "url": "https://swdates.com", "name": "Blog de sexolog\u00eda", "publisher": { "@id": "https://swdates.com/#person" }, "inLanguage": "en-US", "potentialAction": { "@type": "SearchAction", "target": "https://swdates.com/?s={search_term_string}", "query-input": "required name=search_term_string" } }, { "@type": "ImageObject", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage", "url": "https://swdates.com/wp-content/uploads/2020/12/genetica-sexologia-y-bioetica.jpg", "width": 280, "height": 201 }, { "@type": "WebPage", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage", "url": "https://swdates.com/genetica-sexologia-y-bioetica/", "name": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "isPartOf": { "@id": "https://swdates.com/#website" }, "primaryImageOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US" }, { "@type": "BlogPosting", "headline": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "author": { "@type": "Person" }, "publisher": { "@id": "https://swdates.com/#person" }, "description": "GENETICA , SEXOLOGIA Y BIOETICA MEDICO GENETISTA, SEXOLOGO.ACADEMICO DE LA FACULTAD DE MEDICINA UNAM. MIEMBRO NUMERARIO DE LA ACADEMIA NACIONAL MEXICANA DE", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#richSnippet", "isPartOf": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" }, "image": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US", "mainEntityOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" } } ] }8 ofAutism, Spence et al. (1985) studied { "@context": "https://schema.org", "@graph": [ { "@type": [ "Person", "Organization" ], "@id": "https://swdates.com/#person", "name": "Blog de sexolog\u00eda", "logo": { "@type": "ImageObject", "url": false }, "image": { "@type": "ImageObject", "url": false } }, { "@type": "WebSite", "@id": "https://swdates.com/#website", "url": "https://swdates.com", "name": "Blog de sexolog\u00eda", "publisher": { "@id": "https://swdates.com/#person" }, "inLanguage": "en-US", "potentialAction": { "@type": "SearchAction", "target": "https://swdates.com/?s={search_term_string}", "query-input": "required name=search_term_string" } }, { "@type": "ImageObject", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage", "url": "https://swdates.com/wp-content/uploads/2020/12/genetica-sexologia-y-bioetica.jpg", "width": 280, "height": 201 }, { "@type": "WebPage", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage", "url": "https://swdates.com/genetica-sexologia-y-bioetica/", "name": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "isPartOf": { "@id": "https://swdates.com/#website" }, "primaryImageOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US" }, { "@type": "BlogPosting", "headline": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "author": { "@type": "Person" }, "publisher": { "@id": "https://swdates.com/#person" }, "description": "GENETICA , SEXOLOGIA Y BIOETICA MEDICO GENETISTA, SEXOLOGO.ACADEMICO DE LA FACULTAD DE MEDICINA UNAM. MIEMBRO NUMERARIO DE LA ACADEMIA NACIONAL MEXICANA DE", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#richSnippet", "isPartOf": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" }, "image": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US", "mainEntityOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" } } ] }7 { "@context": "https://schema.org", "@graph": [ { "@type": [ "Person", "Organization" ], "@id": "https://swdates.com/#person", "name": "Blog de sexolog\u00eda", "logo": { "@type": "ImageObject", "url": false }, "image": { "@type": "ImageObject", "url": false } }, { "@type": "WebSite", "@id": "https://swdates.com/#website", "url": "https://swdates.com", "name": "Blog de sexolog\u00eda", "publisher": { "@id": "https://swdates.com/#person" }, "inLanguage": "en-US", "potentialAction": { "@type": "SearchAction", "target": "https://swdates.com/?s={search_term_string}", "query-input": "required name=search_term_string" } }, { "@type": "ImageObject", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage", "url": "https://swdates.com/wp-content/uploads/2020/12/genetica-sexologia-y-bioetica.jpg", "width": 280, "height": 201 }, { "@type": "WebPage", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage", "url": "https://swdates.com/genetica-sexologia-y-bioetica/", "name": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "isPartOf": { "@id": "https://swdates.com/#website" }, "primaryImageOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US" }, { "@type": "BlogPosting", "headline": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "author": { "@type": "Person" }, "publisher": { "@id": "https://swdates.com/#person" }, "description": "GENETICA , SEXOLOGIA Y BIOETICA MEDICO GENETISTA, SEXOLOGO.ACADEMICO DE LA FACULTAD DE MEDICINA UNAM. MIEMBRO NUMERARIO DE LA ACADEMIA NACIONAL MEXICANA DE", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#richSnippet", "isPartOf": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" }, "image": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US", "mainEntityOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" } } ] }6 with { "@context": "https://schema.org", "@graph": [ { "@type": [ "Person", "Organization" ], "@id": "https://swdates.com/#person", "name": "Blog de sexolog\u00eda", "logo": { "@type": "ImageObject", "url": false }, "image": { "@type": "ImageObject", "url": false } }, { "@type": "WebSite", "@id": "https://swdates.com/#website", "url": "https://swdates.com", "name": "Blog de sexolog\u00eda", "publisher": { "@id": "https://swdates.com/#person" }, "inLanguage": "en-US", "potentialAction": { "@type": "SearchAction", "target": "https://swdates.com/?s={search_term_string}", "query-input": "required name=search_term_string" } }, { "@type": "ImageObject", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage", "url": "https://swdates.com/wp-content/uploads/2020/12/genetica-sexologia-y-bioetica.jpg", "width": 280, "height": 201 }, { "@type": "WebPage", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage", "url": "https://swdates.com/genetica-sexologia-y-bioetica/", "name": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "isPartOf": { "@id": "https://swdates.com/#website" }, "primaryImageOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US" }, { "@type": "BlogPosting", "headline": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "author": { "@type": "Person" }, "publisher": { "@id": "https://swdates.com/#person" }, "description": "GENETICA , SEXOLOGIA Y BIOETICA MEDICO GENETISTA, SEXOLOGO.ACADEMICO DE LA FACULTAD DE MEDICINA UNAM. MIEMBRO NUMERARIO DE LA ACADEMIA NACIONAL MEXICANA DE", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#richSnippet", "isPartOf": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" }, "image": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US", "mainEntityOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" } } ] }5 2 affected { "@context": "https://schema.org", "@graph": [ { "@type": [ "Person", "Organization" ], "@id": "https://swdates.com/#person", "name": "Blog de sexolog\u00eda", "logo": { "@type": "ImageObject", "url": false }, "image": { "@type": "ImageObject", "url": false } }, { "@type": "WebSite", "@id": "https://swdates.com/#website", "url": "https://swdates.com", "name": "Blog de sexolog\u00eda", "publisher": { "@id": "https://swdates.com/#person" }, "inLanguage": "en-US", "potentialAction": { "@type": "SearchAction", "target": "https://swdates.com/?s={search_term_string}", "query-input": "required name=search_term_string" } }, { "@type": "ImageObject", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage", "url": "https://swdates.com/wp-content/uploads/2020/12/genetica-sexologia-y-bioetica.jpg", "width": 280, "height": 201 }, { "@type": "WebPage", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage", "url": "https://swdates.com/genetica-sexologia-y-bioetica/", "name": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "isPartOf": { "@id": "https://swdates.com/#website" }, "primaryImageOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US" }, { "@type": "BlogPosting", "headline": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "author": { "@type": "Person" }, "publisher": { "@id": "https://swdates.com/#person" }, "description": "GENETICA , SEXOLOGIA Y BIOETICA MEDICO GENETISTA, SEXOLOGO.ACADEMICO DE LA FACULTAD DE MEDICINA UNAM. MIEMBRO NUMERARIO DE LA ACADEMIA NACIONAL MEXICANA DE", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#richSnippet", "isPartOf": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" }, "image": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US", "mainEntityOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" } } ] }4. Linkage { "@context": "https://schema.org", "@graph": [ { "@type": [ "Person", "Organization" ], "@id": "https://swdates.com/#person", "name": "Blog de sexolog\u00eda", "logo": { "@type": "ImageObject", "url": false }, "image": { "@type": "ImageObject", "url": false } }, { "@type": "WebSite", "@id": "https://swdates.com/#website", "url": "https://swdates.com", "name": "Blog de sexolog\u00eda", "publisher": { "@id": "https://swdates.com/#person" }, "inLanguage": "en-US", "potentialAction": { "@type": "SearchAction", "target": "https://swdates.com/?s={search_term_string}", "query-input": "required name=search_term_string" } }, { "@type": "ImageObject", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage", "url": "https://swdates.com/wp-content/uploads/2020/12/genetica-sexologia-y-bioetica.jpg", "width": 280, "height": 201 }, { "@type": "WebPage", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage", "url": "https://swdates.com/genetica-sexologia-y-bioetica/", "name": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "isPartOf": { "@id": "https://swdates.com/#website" }, "primaryImageOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US" }, { "@type": "BlogPosting", "headline": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "author": { "@type": "Person" }, "publisher": { "@id": "https://swdates.com/#person" }, "description": "GENETICA , SEXOLOGIA Y BIOETICA MEDICO GENETISTA, SEXOLOGO.ACADEMICO DE LA FACULTAD DE MEDICINA UNAM. MIEMBRO NUMERARIO DE LA ACADEMIA NACIONAL MEXICANA DE", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#richSnippet", "isPartOf": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" }, "image": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US", "mainEntityOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" } } ] }3 in 34 { "@context": "https://schema.org", "@graph": [ { "@type": [ "Person", "Organization" ], "@id": "https://swdates.com/#person", "name": "Blog de sexolog\u00eda", "logo": { "@type": "ImageObject", "url": false }, "image": { "@type": "ImageObject", "url": false } }, { "@type": "WebSite", "@id": "https://swdates.com/#website", "url": "https://swdates.com", "name": "Blog de sexolog\u00eda", "publisher": { "@id": "https://swdates.com/#person" }, "inLanguage": "en-US", "potentialAction": { "@type": "SearchAction", "target": "https://swdates.com/?s={search_term_string}", "query-input": "required name=search_term_string" } }, { "@type": "ImageObject", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage", "url": "https://swdates.com/wp-content/uploads/2020/12/genetica-sexologia-y-bioetica.jpg", "width": 280, "height": 201 }, { "@type": "WebPage", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage", "url": "https://swdates.com/genetica-sexologia-y-bioetica/", "name": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "isPartOf": { "@id": "https://swdates.com/#website" }, "primaryImageOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US" }, { "@type": "BlogPosting", "headline": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "author": { "@type": "Person" }, "publisher": { "@id": "https://swdates.com/#person" }, "description": "GENETICA , SEXOLOGIA Y BIOETICA MEDICO GENETISTA, SEXOLOGO.ACADEMICO DE LA FACULTAD DE MEDICINA UNAM. MIEMBRO NUMERARIO DE LA ACADEMIA NACIONAL MEXICANA DE", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#richSnippet", "isPartOf": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" }, "image": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US", "mainEntityOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" } } ] }2 { "@context": "https://schema.org", "@graph": [ { "@type": [ "Person", "Organization" ], "@id": "https://swdates.com/#person", "name": "Blog de sexolog\u00eda", "logo": { "@type": "ImageObject", "url": false }, "image": { "@type": "ImageObject", "url": false } }, { "@type": "WebSite", "@id": "https://swdates.com/#website", "url": "https://swdates.com", "name": "Blog de sexolog\u00eda", "publisher": { "@id": "https://swdates.com/#person" }, "inLanguage": "en-US", "potentialAction": { "@type": "SearchAction", "target": "https://swdates.com/?s={search_term_string}", "query-input": "required name=search_term_string" } }, { "@type": "ImageObject", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage", "url": "https://swdates.com/wp-content/uploads/2020/12/genetica-sexologia-y-bioetica.jpg", "width": 280, "height": 201 }, { "@type": "WebPage", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage", "url": "https://swdates.com/genetica-sexologia-y-bioetica/", "name": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "isPartOf": { "@id": "https://swdates.com/#website" }, "primaryImageOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US" }, { "@type": "BlogPosting", "headline": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "author": { "@type": "Person" }, "publisher": { "@id": "https://swdates.com/#person" }, "description": "GENETICA , SEXOLOGIA Y BIOETICA MEDICO GENETISTA, SEXOLOGO.ACADEMICO DE LA FACULTAD DE MEDICINA UNAM. MIEMBRO NUMERARIO DE LA ACADEMIA NACIONAL MEXICANA DE", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#richSnippet", "isPartOf": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" }, "image": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US", "mainEntityOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" } } ] }1 no { "@context": "https://schema.org", "@graph": [ { "@type": [ "Person", "Organization" ], "@id": "https://swdates.com/#person", "name": "Blog de sexolog\u00eda", "logo": { "@type": "ImageObject", "url": false }, "image": { "@type": "ImageObject", "url": false } }, { "@type": "WebSite", "@id": "https://swdates.com/#website", "url": "https://swdates.com", "name": "Blog de sexolog\u00eda", "publisher": { "@id": "https://swdates.com/#person" }, "inLanguage": "en-US", "potentialAction": { "@type": "SearchAction", "target": "https://swdates.com/?s={search_term_string}", "query-input": "required name=search_term_string" } }, { "@type": "ImageObject", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage", "url": "https://swdates.com/wp-content/uploads/2020/12/genetica-sexologia-y-bioetica.jpg", "width": 280, "height": 201 }, { "@type": "WebPage", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage", "url": "https://swdates.com/genetica-sexologia-y-bioetica/", "name": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "isPartOf": { "@id": "https://swdates.com/#website" }, "primaryImageOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US" }, { "@type": "BlogPosting", "headline": "GENETICA , SEXOLOGIA Y BIOETICA - Blog de Sexolog\u00eda y Relaciones Personales", "datePublished": "2020-11-14T20:51:28+01:00", "dateModified": "2020-11-14T20:51:28+01:00", "author": { "@type": "Person" }, "publisher": { "@id": "https://swdates.com/#person" }, "description": "GENETICA , SEXOLOGIA Y BIOETICA MEDICO GENETISTA, SEXOLOGO.ACADEMICO DE LA FACULTAD DE MEDICINA UNAM. MIEMBRO NUMERARIO DE LA ACADEMIA NACIONAL MEXICANA DE", "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#richSnippet", "isPartOf": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" }, "image": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#primaryImage" }, "inLanguage": "en-US", "mainEntityOfPage": { "@id": "https://swdates.com/genetica-sexologia-y-bioetica/#webpage" } } ] }0 of linkage with HLA ( 142800 ), window._wpemojiSettings = {"baseUrl":"https:\/\/s.w.org\/images\/core\/emoji\/13.0.0\/72x72\/","ext":".png","svgUrl":"https:\/\/s.w.org\/images\/core\/emoji\/13.0.0\/svg\/","svgExt":".svg","source":{"concatemoji":"https:\/\/swdates.com\/wp-includes\/js\/wp-emoji-release.min.js?ver=5.5.3"}}; !function(e,a,t){var r,n,o,i,p=a.createElement("canvas"),s=p.getContext&&p.getContext("2d");function c(e,t){var a=String.fromCharCode;s.clearRect(0,0,p.width,p.height),s.fillText(a.apply(this,e),0,0);var r=p.toDataURL();return s.clearRect(0,0,p.width,p.height),s.fillText(a.apply(this,t),0,0),r===p.toDataURL()}function l(e){if(!s||!s.fillText)return!1;switch(s.textBaseline="top",s.font="600 32px Arial",e){case"flag":return!c([127987,65039,8205,9895,65039],[127987,65039,8203,9895,65039])&&(!c([55356,56826,55356,56819],[55356,56826,8203,55356,56819])&&!c([55356,57332,56128,56423,56128,56418,56128,56421,56128,56430,56128,56423,56128,56447],[55356,57332,8203,56128,56423,8203,56128,56418,8203,56128,56421,8203,56128,56430,8203,56128,56423,8203,56128,56447]));case"emoji":return!c([55357,56424,8205,55356,57212],[55357,56424,8203,55356,57212])}return!1}function d(e){var t=a.createElement("script");t.src=e,t.defer=t.type="text/javascript",a.getElementsByTagName("head")[0].appendChild(t)}for(i=Array("flag","emoji"),t.supports={everything:!0,everythingExceptFlag:!0},o=0;o window._wpemojiSettings = {"baseUrl":"https:\/\/s.w.org\/images\/core\/emoji\/13.0.0\/72x72\/","ext":".png","svgUrl":"https:\/\/s.w.org\/images\/core\/emoji\/13.0.0\/svg\/","svgExt":".svg","source":{"concatemoji":"https:\/\/swdates.com\/wp-includes\/js\/wp-emoji-release.min.js?ver=5.5.3"}}; !function(e,a,t){var r,n,o,i,p=a.createElement("canvas"),s=p.getContext&&p.getContext("2d");function c(e,t){var a=String.fromCharCode;s.clearRect(0,0,p.width,p.height),s.fillText(a.apply(this,e),0,0);var r=p.toDataURL();return s.clearRect(0,0,p.width,p.height),s.fillText(a.apply(this,t),0,0),r===p.toDataURL()}function l(e){if(!s||!s.fillText)return!1;switch(s.textBaseline="top",s.font="600 32px Arial",e){case"flag":return!c([127987,65039,8205,9895,65039],[127987,65039,8203,9895,65039])&&(!c([55356,56826,55356,56819],[55356,56826,8203,55356,56819])&&!c([55356,57332,56128,56423,56128,56418,56128,56421,56128,56430,56128,56423,56128,56447],[55356,57332,8203,56128,56423,8203,56128,56418,8203,56128,56421,8203,56128,56430,8203,56128,56423,8203,56128,56447]));case"emoji":return!c([55357,56424,8205,55356,57212],[55357,56424,8203,55356,57212])}return!1}function d(e){var t=a.createElement("script");t.src=e,t.defer=t.type="text/javascript",a.getElementsByTagName("head")[0].appendChild(t)}for(i=Array("flag","emoji"),t.supports={everything:!0,everythingExceptFlag:!0},o=0;o 3 theAutismDiagnostic Instrument-Revised (ADI-R), theAutismDiagnostic 2 Scale (ADOS), and psychometric 1, Klauck et al. (1997) 0 141autistic /* */ 9 from /* */ 8 simplex and 18 multiplex /* */ 7; 131 /* */ 6 met all /* */ 5 ADI-R algorithm /* */ 4 forautismand 10 /* */ 3 /* */ 2 a broader phenotype ofautism. /* */ 1 amplification of the CCG repeat /* */ 0 fragile X locus, hybridization to 9 FMR1 cDNA probe, and hybridization to 8 probes from the neighborhood of the FMR1 gene, the authors 7 no 6 5 in 139 4 (3%) from 122 2. In 1 multiplex 1 with 0 9 8 no dysmorphic 7 of 6 X syndrome (1 male 5 4 of 3 ADI-algorithm 2, 1 1 male with slight 0 /* */ 9 /* */ 8 /* */ 7 ADI-R testing, and 1 /* */ 6autistic /* */ 5), the FRAXA full-mutation- /* */ 4 CCG-repeat /* */ 3 /* */ 2 genotype was not correlated with theautismphenotype. /* */ 1 /* */ 0 revealed a mosaic 9 of methylation 8 FMR1 gene locus 7 2 sons of the 6, indicating 5 a partly 4 gene. Klauck et al. (1997) concluded that the 3 ofautismwith fragile X at Xq27.2 is nonexistent and excluded this location as a candidate gene forautism.
Cytogenetics
Lopreiato and Wulfsberg (1992) described 1 chromosomal rearrangement in a 6.5-0- var cli_flush_cache = true; 9 boy withautismwho was var cli_flush_cache = true; 8 var cli_flush_cache = true; 7 var cli_flush_cache = true; 6 minimal dysmorphism. The rearrangement seen in var cli_flush_cache = true; 5 cell examined var cli_flush_cache = true; 4 chromosomes 1, 7 and 21: var cli_flush_cache = true; 3, XY, -1, -7, -21, t(1;7;21)(1p22.1-qter::21q22. var cli_flush_cache = true; 2-qter; 7pter-q11.23::7q36.1-qter; 21pter-q22. var cli_flush_cache = true; 1::7q11.23-q36.1::1pter-p22.1).
Vincent et al. (2006) reported 2 brothers withautismwho var cli_flush_cache = true; 0 carried a paracentric inversion of chromosome 4p, inv(9)(p12-p15.8), inherited from an unaffected 7 and unaffected maternal grandfather. 6 detailed molecular 5 4 that the proximal breakpoint on 4p12 3 a cluster of GABA receptor genes, 2 the GABRA4 gene ( 137141 ), which has been implicated inautism( Ma et al., 2005 ; Collins et al., 2006 ). Maestrini et al. (1999) 1 no 0 or linkage to the GABRB3 gene in 9 8 comprising 174 7 withautism.
Moessner et al. (2007) 6 deletions 5 SHANK3 gene ( 606230 ) on chromosome 22q13 in 4 (3.2%) of 1 unrelated 0 with anautismspectrum /* */ 9. The deletions ranged in /* */ 8 from 277 kb to /* */ 7.36 Mb; 1 /* */ 6 /* */ 5 had a 1. /* */ 4-Mb duplication at chromosome 20q13.33. The /* */ 3 /* */ 2 /* */ 1 nonverbal and /* */ 0 poor social interactions and repetitive behaviors. Two had 9 developmental delay and 8 dysmorphic 7. A fourth 6 with a de novo missense mutation 5 SHANK3 gene hadautism-like 4 3 had diagnostic scores above the cutoff forautism; she was conceived by in vitro fertilization. See 2 the chromosome 22q13.1 deletion syndrome ( 606232 ).
Copy 0 Variation
9 8-7 microarray 6, Marshall et al. (2008) 5 277 unbalanced copy 4 variations (CNV), 3 deletion, duplication, translocation, and inversion, in 189 (2%) of 427 1 withautismspectrum 0 (ASD). These 9 8 7 6 in 5 of about 1,600 controls, 4 3 2 1 carried many CNV. 0 most variants 9 inherited 8 7, 27 6 had de novo alterations, 5 ( 4%) 3 2 had 2 or 1 0. Marshall et al. (2008) detected (function($) { function setup_collapsible_submenus() { var $menu = $('#mobile_menu'), top_level_link = '#mobile_menu .menu-item-has-children > a'; $menu.find('a').each(function() { $(this).off('click'); if ( $(this).is(top_level_link) ) { $(this).attr('href', '#'); } if ( ! $(this).siblings('.sub-menu').length ) { $(this).on('click', function(event) { $(this).parents('.mobile_nav').trigger('click'); }); } else { $(this).on('click', function(event) { event.preventDefault(); $(this).parent().toggleClass('visible'); }); } }); } $(window).load(function() { setTimeout(function() { setup_collapsible_submenus(); }, 700); }); })(jQuery); 9 loci with recurrent or overlapping CNV in unrelated (function($) { function setup_collapsible_submenus() { var $menu = $('#mobile_menu'), top_level_link = '#mobile_menu .menu-item-has-children > a'; $menu.find('a').each(function() { $(this).off('click'); if ( $(this).is(top_level_link) ) { $(this).attr('href', '#'); } if ( ! $(this).siblings('.sub-menu').length ) { $(this).on('click', function(event) { $(this).parents('.mobile_nav').trigger('click'); }); } else { $(this).on('click', function(event) { event.preventDefault(); $(this).parent().toggleClass('visible'); }); } }); } $(window).load(function() { setTimeout(function() { setup_collapsible_submenus(); }, 700); }); })(jQuery); 8. Of (function($) { function setup_collapsible_submenus() { var $menu = $('#mobile_menu'), top_level_link = '#mobile_menu .menu-item-has-children > a'; $menu.find('a').each(function() { $(this).off('click'); if ( $(this).is(top_level_link) ) { $(this).attr('href', '#'); } if ( ! $(this).siblings('.sub-menu').length ) { $(this).on('click', function(event) { $(this).parents('.mobile_nav').trigger('click'); }); } else { $(this).on('click', function(event) { event.preventDefault(); $(this).parent().toggleClass('visible'); }); } }); } $(window).load(function() { setTimeout(function() { setup_collapsible_submenus(); }, 700); }); })(jQuery); 7, CNV at chromosome 16p11.2 (AUTS14; see 611913 ) was (function($) { function setup_collapsible_submenus() { var $menu = $('#mobile_menu'), top_level_link = '#mobile_menu .menu-item-has-children > a'; $menu.find('a').each(function() { $(this).off('click'); if ( $(this).is(top_level_link) ) { $(this).attr('href', '#'); } if ( ! $(this).siblings('.sub-menu').length ) { $(this).on('click', function(event) { $(this).parents('.mobile_nav').trigger('click'); }); } else { $(this).on('click', function(event) { event.preventDefault(); $(this).parent().toggleClass('visible'); }); } }); } $(window).load(function() { setTimeout(function() { setup_collapsible_submenus(); }, 700); }); })(jQuery); 6 in (function($) { function setup_collapsible_submenus() { var $menu = $('#mobile_menu'), top_level_link = '#mobile_menu .menu-item-has-children > a'; $menu.find('a').each(function() { $(this).off('click'); if ( $(this).is(top_level_link) ) { $(this).attr('href', '#'); } if ( ! $(this).siblings('.sub-menu').length ) { $(this).on('click', function(event) { $(this).parents('.mobile_nav').trigger('click'); }); } else { $(this).on('click', function(event) { event.preventDefault(); $(this).parent().toggleClass('visible'); }); } }); } $(window).load(function() { setTimeout(function() { setup_collapsible_submenus(); }, 700); }); })(jQuery); 5 (1%) of 427 (function($) { function setup_collapsible_submenus() { var $menu = $('#mobile_menu'), top_level_link = '#mobile_menu .menu-item-has-children > a'; $menu.find('a').each(function() { $(this).off('click'); if ( $(this).is(top_level_link) ) { $(this).attr('href', '#'); } if ( ! $(this).siblings('.sub-menu').length ) { $(this).on('click', function(event) { $(this).parents('.mobile_nav').trigger('click'); }); } else { $(this).on('click', function(event) { event.preventDefault(); $(this).parent().toggleClass('visible'); }); } }); } $(window).load(function() { setTimeout(function() { setup_collapsible_submenus(); }, 700); }); })(jQuery); 4 and none of 1,652 controls (p = (function($) { function setup_collapsible_submenus() { var $menu = $('#mobile_menu'), top_level_link = '#mobile_menu .menu-item-has-children > a'; $menu.find('a').each(function() { $(this).off('click'); if ( $(this).is(top_level_link) ) { $(this).attr('href', '#'); } if ( ! $(this).siblings('.sub-menu').length ) { $(this).on('click', function(event) { $(this).parents('.mobile_nav').trigger('click'); }); } else { $(this).on('click', function(event) { event.preventDefault(); $(this).parent().toggleClass('visible'); }); } }); } $(window).load(function() { setTimeout(function() { setup_collapsible_submenus(); }, 700); }); })(jQuery); 3.002). (function($) { function setup_collapsible_submenus() { var $menu = $('#mobile_menu'), top_level_link = '#mobile_menu .menu-item-has-children > a'; $menu.find('a').each(function() { $(this).off('click'); if ( $(this).is(top_level_link) ) { $(this).attr('href', '#'); } if ( ! $(this).siblings('.sub-menu').length ) { $(this).on('click', function(event) { $(this).parents('.mobile_nav').trigger('click'); }); } else { $(this).on('click', function(event) { event.preventDefault(); $(this).parent().toggleClass('visible'); }); } }); } $(window).load(function() { setTimeout(function() { setup_collapsible_submenus(); }, 700); }); })(jQuery); 2autismloci (function($) { function setup_collapsible_submenus() { var $menu = $('#mobile_menu'), top_level_link = '#mobile_menu .menu-item-has-children > a'; $menu.find('a').each(function() { $(this).off('click'); if ( $(this).is(top_level_link) ) { $(this).attr('href', '#'); } if ( ! $(this).siblings('.sub-menu').length ) { $(this).on('click', function(event) { $(this).parents('.mobile_nav').trigger('click'); }); } else { $(this).on('click', function(event) { event.preventDefault(); $(this).parent().toggleClass('visible'); }); } }); } $(window).load(function() { setTimeout(function() { setup_collapsible_submenus(); }, 700); }); })(jQuery); 1 (function($) { function setup_collapsible_submenus() { var $menu = $('#mobile_menu'), top_level_link = '#mobile_menu .menu-item-has-children > a'; $menu.find('a').each(function() { $(this).off('click'); if ( $(this).is(top_level_link) ) { $(this).attr('href', '#'); } if ( ! $(this).siblings('.sub-menu').length ) { $(this).on('click', function(event) { $(this).parents('.mobile_nav').trigger('click'); }); } else { $(this).on('click', function(event) { event.preventDefault(); $(this).parent().toggleClass('visible'); }); } }); } $(window).load(function() { setTimeout(function() { setup_collapsible_submenus(); }, 700); }); })(jQuery); 0 9 to 8 retardation loci. Marshall et al. (2008) concluded that structural gene variants 7 6 sufficiently 5 frequency influencingautismspectrum 4 to 3 that cytogenetic and microarray analyses be 2 in routine 1 workup.
Cusco et al. (2009) analyzed 0 Spanish 9 with idiopathic ASD by array CGH 8. 7 6 of the 238 detected CNVs (5, 89 kb-2.4 Mb) 3 2 1 in 12 (12.5%) of 0 ASD 9. The CNVs consisted of 10 duplications 8 deletions. In 5 7 with parental samples 6, CNVs 5 inherited from 4 3. Two CNVs mapped to 2 with 1 reported ASD candidates, KIAA0442 ( 607270 ) on chromosome 7q11.22 and GRM8 ( 601116 ) on chromosome 7q31.0. Of the 24 genes [if IE 6]> Sebat et al. (2007) [if IE 7]> Pinto et al. (2010) analyzed the genomewide [if lt IE 9]> Levy et al. (2011) studied 887 #et-top-navigation 0 from the Simons Simplex .container 9 of .container 8 .container 7 functioning ASD .container 6. They .container 5 .container 4 de novo CNVs in .container 3 probands ( .container 2 .container 1% of probands). .container 0 #main-header 9 recurrent. Variation #main-header 8 16p11.2 locus was detected #main-header 7 than 1% of #main-header 6 (10 of 858), with deletions #main-header 5 in 6 and duplications in #main-header 4. #main-header 3, the duplication at 7q11.2 of the Williams syndrome #main-header 2 ( 609757 ) was #main-header 1 seen as a recurrent CNV. Levy et al. (2011) #main-header 0 that the .et_post_meta_wrapper 9 of .et_post_meta_wrapper 8% of ASD probands with de novo .et_post_meta_wrapper 7 .et_post_meta_wrapper 6 with 2% in unaffected sibs was .et_post_meta_wrapper 5 .et_post_meta_wrapper 4 .et_post_meta_wrapper 3. They speculated that .et_post_meta_wrapper 2 .et_post_meta_wrapper 1 incidence of .et_post_meta_wrapper 0% .entry-content 9 than .entry-content 8% reported by Sebat et al. (2007) .entry-content 7 to .entry-content 6 functioningautismgroup .entry-content 5 cohort or to smaller .entry-content 4 .entry-content 3 .entry-content 2. .entry-content 1 their .entry-content 0 and the Publisher datos estructurados 9 literature, Levy et al. (2011) proposed Publisher datos estructurados 8 of ‘asymmetries,’ or Publisher datos estructurados 7 biases, in simplex Publisher datos estructurados 6 withautism. Publisher datos estructurados 5 Publisher datos estructurados 4 incidence of de novo copy Publisher datos estructurados 3 mutation in Publisher datos estructurados 2 with ASDs from simplex Publisher datos estructurados 1 than Publisher datos estructurados 0 sibs. fin publisher 9 fin publisher 8 incidence of de novo copy fin publisher 7 mutation in fin publisher 6 with ASDs from simplex fin publisher 5 than in fin publisher 4 with ASDs from multiplex fin publisher 3. For transmitted fin publisher 2 fin publisher 1, duplications fin publisher 0 outweigh deletions; deletions outweigh duplications fecha publicacion y modificacion, d.estructurados9 de novo fecha publicacion y modificacion, d.estructurados8 in fecha publicacion y modificacion, d.estructurados7 with ASDs. fecha publicacion y modificacion, d.estructurados6 fecha publicacion y modificacion, d.estructurados5 of transmission distortion for ultrarare fecha publicacion y modificacion, d.estructurados4 to fecha publicacion y modificacion, d.estructurados3 with ASDs; this bias arises from fecha publicacion y modificacion, d.estructurados2 fecha publicacion y modificacion, d.estructurados1 the sib is an unaffected male. Females are fecha publicacion y modificacion, d.estructurados0 fin fecha 9 be fin fecha 8 with ASDs than are males. fin fecha 7 proportion of females with ASDs have detectable de novo copy fin fecha 6 fin fecha 5 than do males with ASDs, and the fin fecha 4 are fin fecha 3. Levy et al. (2011) fin fecha 2 that females are fin fecha 1autism fin fecha 0 .et_post_meta_wrapper 9 .et_post_meta_wrapper 8 a mechanism.
Sanders et al. (2011) examined 1,124 ASD simplex .et_post_meta_wrapper 7 from the Simons Simplex .et_post_meta_wrapper 6. .et_post_meta_wrapper 5 of the .et_post_meta_wrapper 4 was comprised of a single proband, unaffected .et_post_meta_wrapper 3, and in most kindreds an unaffected sib. Sanders et al. (2011) .et_post_meta_wrapper 2 .et_post_meta_wrapper 1 .et_post_meta_wrapper 0 of ASD with de novo duplications of 7q11.23. .et_pb_post 9 .et_pb_post 8 .et_pb_post 7 recurrent de novo CNVs at 5 .et_pb_post 6 .et_pb_post 5, .et_pb_post 4 16p13.2. .et_pb_post 3, .et_pb_post 2 de novo CNVs conferred substantial .et_pb_post 1 (odds ratio = 5.6; CI = 2.6-12. .et_pb_post 0, p = 2. #left-area 9 x 10(-7)). Sanders et al. (2011) #left-area 8 that there are #left-area 7 to 234 ASD- #left-area 6 CNV #left-area 5 #left-area 4 human genome and #left-area 3 compelling #left-area 2, #left-area 1 on cumulative #left-area 0, for end .et_pb_widget 9 of end .et_pb_widget 8 de novo end .et_pb_widget 7 at 7q11.23, 15q11.2-q13.1 (see 608636 ), 16p11.2, and neurexin-1 ( 600565 ). Sanders et al. (2011) end .et_pb_widget 6 that probands carrying a 16p11.2 or 7q11.23 de novo CNV end .et_pb_widget 5 indistinguishable from the end .et_pb_widget 4 ASD group with respect to IQ, ASD severity, or categoricalautism end .et_pb_widget 3. end .et_pb_widget 2, they did end .et_pb_widget 1 relationship between end .et_pb_widget 0 weight and 16p11.2 deletions and duplications. When copy end .et_pb_widget 9 was end .et_pb_widget 8 as an ordinal variable, BMI diminished as 16p11.2 copy end .et_pb_widget 7 end .et_pb_widget 6 (p = end .et_pb_widget 5.02).
Vaags et al. (2012) reported end .et_pb_widget 4 end .et_pb_widget 3 end .et_pb_widget 2 1 or end .et_pb_widget 1 members hadautismspectrum end .et_pb_widget 0 end .et_pb_widget 9 heterozygous deletions of chromosome 14q affecting the NRXN3 gene ( 600567 ). The deletions end .et_pb_widget 8 all end .et_pb_widget 7 and ranged from end .et_pb_widget 6 to 336 kb. One deletion affected end .et_pb_widget 5 the NRXN3 alpha isoform, whereas end .et_pb_widget 4 affected end .et_pb_widget 3 the alpha and beta isoforms. Two end .et_pb_widget 2 end .et_pb_widget 1 ascertained from 1,158 Canadian end .et_pb_widget 0 with ASD who end #sidebar 9 screened for copy end #sidebar 8 variations end #sidebar 7 the genome. The third end #sidebar 6 was 1 of 1,368 ASD end #sidebar 5 screened, and the fourth was 1 of 1,796 ASD end #sidebar 4 screened. The phenotype was variable, end #sidebar 3 end #sidebar 2-functioning Asperger syndrome to fullautismwith some pervasive developmental and behavioral end #sidebar 1. In 1 end #sidebar 0, the deletion occurred de novo. #content-area 9 #content-area 8 #content-area 7, the deletion was inherited from a #content-area 6; 1 #content-area 5 had a broaderautismphenotype, 1 self-reported #content-area 4autistic-like #content-area 3, and 1 was #content-area 2. In 1 #content-area 1, 2 #content-area 0 trizygotic triplets withautismcarried the deletion; the third unaffected .container 9 .container 8 carry the deletion. Small deletions affecting .container 7 the alpha isoform .container 6 .container 5 .container 4 of 15,122 controls. The report .container 3 that deletions affecting the NRXN3 gene .container 2 predispose to .container 1 ofautismspectrum .container 0, #main-content 9 segregation patterns #main-content 8 #main-content 7 #main-content 6 #main-content 5 penetrance and expressivity at this locus.
Loirat et al. (2010) reported #main-content 4 unrelated boys with heterozygous de novo deletions in chromosome 17q12 (see 614527 ) who had cystic or hyperechogenic kidneys andautism. Their 17q12 deletions ranged from 1.5 to 1. #main-content 3 Mb, and included LHX1 ( 601999 ), HNF1B ( 189907 ), and 19 #main-content 2 genes; sequencing of the LHX1 gene #main-content 1 #main-content 0 boys and 32 end .fwidget 9 end .fwidget 8 withautismrevealed no mutations. Loirat et al. (2010) concluded thatautism end .fwidget 7 end .fwidget 6 manifestation end .fwidget 5 HNF1B deletion.
Moreno-De-Luca et al. (2010) end .fwidget 4 cytogenomic array end .fwidget 3 in a discovery end .fwidget 2 of end .fwidget 1 with neurodevelopmental end .fwidget 0 and detected a recurrent 1. end .footer-widget 9-Mb deletion at chromosome 17q12 in 18 of 15,749 end .footer-widget 8, end .footer-widget 7 6 withautismorautistic end .footer-widget 6; the deletion was not end .footer-widget 5 end .footer-widget 4,519 controls. In end .footer-widget 3 end .footer-widget 2-up end .footer-widget 1, end .footer-widget 0 deletion was end .fwidget 9 in 2 of 1,182 end .fwidget 8 withautismspectrum end .fwidget 7 and/or neurocognitive impairment, and in end .fwidget 6 of 6,340 schizophrenia (see 181500 ) end .fwidget 5, end .fwidget 4 was not end .fwidget 3 end .fwidget 2,929 controls (corrected p = 7.37 x 10 (-5)). Moreno-De-Luca et al. (2010) concluded that deletion 17q12 is a recurrent, pathogenic CNV that confers a end .fwidget 1 end .fwidget 0 forautismspectrum end .footer-widget 9 and schizophrenia, and that 1 or end .footer-widget 8 of the 15 genes end .footer-widget 7 deleted interval is dosage- end .footer-widget 6 and end .footer-widget 5 for end .footer-widget 4 end .footer-widget 3 end .footer-widget 2 end .footer-widget 1.
Luo et al. (2012) interrogated gene expression in lymphoblasts from 439 end .footer-widget 0 from 244 end .fwidget 9 with discordant siblings end .fwidget 8 Simons Simplex end .fwidget 7 end .fwidget 6 that end .fwidget 5 frequency of end .fwidget 4 misexpressed genes, which they end .fwidget 3 outliers, end .fwidget 2 differ between probands and unaffected sibs. end .fwidget 1, in probands, end .fwidget 0 not their unaffected sibs, the group of outlier genes was end .footer-widget 9 enriched in neural- end .footer-widget 8 pathways, end .footer-widget 7 neuropeptide signaling, synaptogenesis, and cell adhesion. The outlier genes clustered end .footer-widget 6 end .footer-widget 5 end .footer-widget 4 de novo CNVs and end .footer-widget 3 used for the prioritization of end .footer-widget 2 CNVs of potential significance. end .footer-widget 1 nonrecurrent CNVs with end .footer-widget 0 gene expression alterations #footer-widgets 9 #footer-widgets 8, #footer-widgets 7 deletions in chromosome #footer-widgets 6 3q27, 3p13, and 3p26 and duplications at 2p15, suggesting these as potential ASD loci.
See SHANK1 ( 604999 ) for #footer-widgets 5 of a #footer-widgets 4 #footer-widgets 3 between heterozygous deletions involving the SHANK1 gene on chromosome 19q13 and susceptibility to #footer-widgets 2-functioningautism.
Krumm et al. (2013) #footer-widgets 1 disruptive, genic #footer-widgets 0 CNVs .container 9 411 .container 8 affected by sporadicautismspectrum .container 7 from the Simons Simplex .container 6 .container 5 .container 4 exome sequence .container 3 and CoNIFER (Copy .container 2 Inference from Exome Reads). .container 1 .container 0 density SNP microarrays, the authors’ Footer Info 9 yielded Footer Info 8 2 Footer Info 7 Footer Info 6 smaller genic Footer Info 5 CNVs. Krumm et al. (2013) Footer Info 4 that affected probands inherited Footer Info 3 CNVs than did their sibs (453 vs 394, p = Footer Info 2.004; odds ratio = 1.19) and that the probands’ CNVs affected Footer Info 1 genes (921 vs 726, p = Footer Info 0.02; odds ratio = 1.30). These smaller CNVs (median .container 9 18 kb) .container 8 transmitted preferentially from the .container 7 (136 maternal vs .container 6 paternal, p = .container 5.02), .container 4 this bias occurred .container 3 affected .container 2. .container 1 burden of inherited CNVs was .container 0 primarily by sib pairs with discordant social #main-footer 9 phenotypes, which contrasts with #main-footer 8 #main-footer 7 the phenotypes #main-footer 6 #main-footer 5 #main-footer 4 matched or #main-footer 3 #main-footer 2. In a #main-footer 1 #main-footer 0, the inherited CNVs, de novo CNVs, and de novo single-nucleotide variants all independently contributed to #et-main-area 9 ofautism(p #et-main-area 8 #et-main-area 7.05).
Poultney et al. (2013) used the eXome Hidden Markov #et-main-area 6 (XHMM) #et-main-area 5 transmission #et-main-area 4 and validation by molecular #et-main-area 3 #et-main-area 2 that small CNVs encompassing as few as #et-main-area 1 exons #et-main-area 0 reliably #page-container 9 from #page-container 8-exome #page-container 7. They #page-container 6 this #page-container 5 to anautismcase- #page-container 4 #page-container 3 of 811 #page-container 2 ( #page-container 1 per- #page-container 0 googleoff: all9 depth = 161) and googleoff: all8 googleoff: all7 googleoff: all6 googleoff: all5 burden of googleoff: all4 (minor allele frequency (MAF) 1% or googleoff: all3) 1- to 30-kb CNVs, 1- to 30-kb deletions, and 1- to 10-kb deletions in ASD. CNVs googleoff: all2 1 to 30 kb googleoff: all1 googleoff: all0 hit googleon: all9 single gene, googleon: all8 Poultney et al. (2013) googleon: all7 enrichment for disruption of genes in cytoskeletal and autophagy pathways in ASD. Poultney et al. (2013) concluded that googleon: all6 1- to 30-kb exonic deletions googleon: all5 contribute to googleon: all4 in googleon: all3 7% googleon: all2 with ASD.
Molecular Genetics
Gauthier et al. (2011) googleon: all1 a heterozygous 1-bp deletion (2733delT) googleon: all0 NRXN2 gene ( 600566 ) on chromosome 11q13 in a boy of European ancestry withautismspectrum Global site tag (gtag.js) - Google Analytics 9. The mutation resulted in Global site tag (gtag.js) - Google Analytics 8 termination. In vitro Global site tag (gtag.js) - Google Analytics 7 expression Global site tag (gtag.js) - Google Analytics 6 in COS-7 cells Global site tag (gtag.js) - Google Analytics 5 that the mutant protein was unable to bind its Global site tag (gtag.js) - Google Analytics 4 Global site tag (gtag.js) - Google Analytics 3, and in vitro Global site tag (gtag.js) - Google Analytics 2 in neuronal Global site tag (gtag.js) - Google Analytics 1 Global site tag (gtag.js) - Google Analytics 0 a This site is running CAOS: Complete Analytics Optimization Suite for Wordpress 9 synaptogenic This site is running CAOS: Complete Analytics Optimization Suite for Wordpress 8 with lack of clustering of postsynaptic This site is running CAOS: Complete Analytics Optimization Suite for Wordpress 7. The findings This site is running CAOS: Complete Analytics Optimization Suite for Wordpress 6 This site is running CAOS: Complete Analytics Optimization Suite for Wordpress 5 a This site is running CAOS: Complete Analytics Optimization Suite for Wordpress 4 This site is running CAOS: Complete Analytics Optimization Suite for Wordpress 3. The mutation was inherited from the This site is running CAOS: Complete Analytics Optimization Suite for Wordpress 2’s father, who had This site is running CAOS: Complete Analytics Optimization Suite for Wordpress 1 language delay. A maternal aunt of This site is running CAOS: Complete Analytics Optimization Suite for Wordpress 0’s had schizophrenia, {buthowever} DNA was not {availableout thereobtainableaccessible} from her. The {patientaffected person} was {identifiedrecognized} from a cohort of 142 {patientssufferers} withautismwho {werehave beenhad been} screened for mutations {in thewithin the} NRXN1 ( 600565 ), NRXN2, and NRXN3 genes.
Sanders et al. (2012) used {wholeentirecomplete}-exome sequencing of 928 {individualspeople}, {includingtogether with} 200 phenotypically discordant sib pairs, to {demonstrateshowrevealexhibitdisplay} that {highlyextremely} disruptive nonsense and splice {sitewebsiteweb site} de novo mutations in {brainmind}-expressed genes are {associated withrelated to}autismspectrum {disordersissuesproblems} and carry {largegiantmassive} {effectsresults}. On {the basisthe ideathe premise} of mutation {ratescharges} in unaffected {individualspeople}, they demonstrated that {multiplea number of} {independentunbiasedimpartial} de novo single-nucleotide variants in {the samethe identical} gene {amongamongst} unrelated probands reliably identifies {riskdangerthreat} alleles, {providingoffering} {a cleara transparent} path {forwardahead} for gene discovery. {AmongAmongst} {a totala complete} of 279 {identifiedrecognized} de novo coding mutations, there was a single {instanceoccasion} in probands, and none in sibs, {in whichby whichduring whichthrough whichwherein} 2 {independentunbiasedimpartial} nonsense variants disrupt {the samethe identical} gene, SCN2A ( 182390 ). Sanders et al. (2012) {combinedmixed} all de novo {eventsoccasions} {in theirof their} {samplepattern} with {thosethese} {identifiedrecognized} {in thewithin the} {studyresearchexamine} of ‘Roak et al. (2012) and {observednoticed} from {a totala complete} of 414 probands 2 {additionalfurtherextra} genes carrying 2 {highlyextremely} disruptive mutations {eachevery}, KATNAL2 ( 614697 ) and CHD8 ( 610528 ).
‘Roak et al. (2012) {performedcarried out} {wholeentirecomplete}-exome sequencing for {parentmother or fatherfather or motherdad or mummum or dadguardian}-{childbabyyoungsterlittle one} trios exhibiting sporadicautismspectrum {disordersissuesproblems}, {includingtogether with} 189 new trios and 20 that {werehave beenhad been} {previouslybeforehand} reported ( ‘Roak et al., 2011 ). {In additionAs well as}, ‘Roak et al. (2012) sequenced the exomes {of 50of fifty} unaffected sibs {corresponding tosimilar tocomparable toakin toequivalent to} 31 of {the newthe brand new} and 19 of the {previouslybeforehand} reported trios, for {a totala complete} of 677 {individualparticular person} exomes from 209 {familieshouseholds}. ‘Roak et al. (2012) {showedconfirmed} that de novo {pointlevel} mutations are overwhelmingly paternal in origin ({4four}:1 bias) and positively correlated with paternal age, {consistent withaccording toin keeping within line within step withper} the modest {increasedelevated} {riskdangerthreat} {for childrenfor youngstersfor kids} of older fathers to developautismspectrum {disordersissuesproblems}. {MoreoverFurthermore}, 39% ({49forty nine} of 126) of {the mostprobably the mostessentially the most} {severeextreme} or disruptive de novo mutations mapped to a {highlyextremely} interconnected beta-catenin ( 116806 )/chromatin {remodelingtransformingreworking} protein {networkcommunity} ranked {significantlyconsiderably} forautismcandidate genes. In proband exomes, recurrent protein-altering mutations {werehave beenhad been} {observednoticed} in 2 genes: CHD8 and NTNG1. Mutation screening of 6 candidate genes in 1,703 ASD probands {identifiedrecognized} {additionalfurtherextra} de novo, protein-altering mutations in GRIN2B ( 138252 ), LAMC3 ( 604349 ), and SCN1A ( 182389 ). {CombinedMixed} with copy {numberquantity} {dataknowledgeinformation}, these {dataknowledgeinformation} indicated {extremeexcessive} locus heterogeneity in ASD. ‘Roak et al. (2012) concluded that their {analysisevaluation} predicted {extremeexcessive} locus heterogeneity underlying the genetic etiology ofautism. {UnderBeneathUnderneathBelow} a strict sporadic {disorderdysfunction}-de novo mutation {modelmannequin}, if 20 to 30% of the de novo {pointlevel} mutations are {consideredthought-aboutthought of} to be pathogenic, {they couldthey mightthey may} estimate between 384 and 821 loci. {FurthermoreMoreover}, 1 {individualparticular person} inherited {3three} {rareuncommon} gene disruptive CNVs and carried 2 de novo truncating mutations.
Neale et al. (2012) assessed the {rolepositionfunction} of de novo mutations inautismspectrum {disordersissuesproblems} by sequencing the exomes of ASD {casesinstancescircumstances} and their {parentsmother and fatherdad and mom} ({175one hundred seventy fivea hundred seventy five} trios). Fewer than half of the {casesinstancescircumstances} ({46forty six}.{3three}%) carried a missense or nonsense de novo variant, and {the overallthe general} {ratepricefeecharge} of mutation was {onlysolely} modestly {highergreaterlargerincreased} than the {expectedanticipated} {ratepricefeecharge}. In {contrastdistinction}, the proteins encoded by genes that harbored de novo missense or nonsense mutations {showedconfirmed} {a highera betterthe next} {degreediploma} of connectivity {amongamongst} themselves and to {previousearlier} ASD genes as {indexedlisted} by protein-protein {interactioninterplay} screens. The small {increaseimproveenhance} {in thewithin the} {ratepricefeecharge} of de novo {eventsoccasions}, when taken {together withalong with} the protein {interactioninterplay} {resultsoutcomes}, are {consistent withaccording toin keeping within line within step withper} an {importantessentialnecessaryvital} {buthowever} {limitedrestricted} {rolepositionfunction} for de novo {pointlevel} mutations in ASD, {similar tojust likemuch like} that documented for de novo copy {numberquantity} variants. Genetic {modelsfashions} incorporating {dataknowledgeinformation} indicated that {most of thea lot of themany of the} {observednoticed} de novo {eventsoccasions} are unconnected to ASD; {those thatpeople whothose who} do confer {riskdangerthreat} are distributed {acrossthroughout} many genes and are incompletely penetrant (i.e., not {necessarilyessentially} {sufficientenoughadequateample} for {diseaseillness}). Neale et al. (2012) concluded that their {resultsoutcomes} supported polygenic {modelsfashions} {in whichby whichduring whichthrough whichwherein} spontaneous coding mutations in any of {a large number ofnumerousa lot of} genes {increaseswill increase} {riskdangerthreat} by 5- {to 20to twenty}-fold. {DespiteRegardless of} the {challengeproblem} posed by such {modelsfashions}, {resultsoutcomes} from de novo {eventsoccasions} and {a largea big} parallel case-{controlmanagement} {studyresearchexamine} {providedofferedsupplied} {strongrobuststurdy} {evidenceproof} in favor of CHD8 and KATNAL2 as {genuinereal}autism{riskdangerthreat} {factorselementscomponents}.
‘Roak et al. (2012) developed a modified molecular inversion probe {methodtechniquemethodology} enabling {ultraextremely}-low-{costvalueprice} candidate gene resequencing in very {largegiantmassive} cohorts. To {demonstrateshowrevealexhibitdisplay} {the powerthe facilitythe ability} of this {approachstrategymethod}, ‘Roak et al. (2012) captured and sequenced {44forty four} candidate genes in 2,446 ASD probands, and {discoveredfound} 27 de novo {eventsoccasions} in {16sixteen} genes, {59fifty nine}% of {which arethat are} predicted to truncate proteins or disrupt splicing. ‘Roak et al. (2012) estimated that recurrent disruptive mutations in 6 genes-CHD8, DYRK1A ( 600855 ), GRIN2B, TBR1 ( 604616 ), PTEN ( 601728 ), and TBL1XR1 ( 608628 )-{maymightcould} contribute to 1% of sporadicautismspectrum {disordersissuesproblems}. ‘Roak et al. (2012) concluded that their {dataknowledgeinformation} supported associations between {specificparticular} genes and reciprocal subphenotypes (CHD8-macrocephaly and DYRK1A-microcephaly) and replicated the {importancesignificance} of a beta-catenin/chromatin-{remodelingtransformingreworking} {networkcommunity} to ASD etiology.
Jiang et al. (2013) used {wholeentirecomplete}-genome sequencing {to examineto look at} 32 {familieshouseholds} with ASD to detect de novo or {rareuncommon} inherited genetic variants predicted to be deleterious (loss-of-{functionperformoperate} and damaging missense mutations). {AmongAmongst} ASD probands, Jiang et al. (2013) {identifiedrecognized} deleterious de novo mutations in 6 of 32 (19%) {familieshouseholds} and X-linked or autosomal inherited alterations in 10 of 32 (31%) {familieshouseholds} (some had {combinationsmixturescombos} of mutations). The proportion of {familieshouseholds} {identifiedrecognized} with such putative mutations was {largerbigger} than had been reported; this yield was {in partpartiallypartly} {due to thebecause of theas a result of} {comprehensivecomplete} and uniform {coverageprotection} afforded by {wholeentirecomplete}-genome sequencing. Deleterious variants {werehave beenhad been} {found inpresent in} {4four} unrecognized, 9 {knownrecognizedidentified}, {and 8and eight} candidate ASD {riskdangerthreat} genes. Examples {includeembraceembody} CAPRIN1 ( 601178 ), AFF2 ( 300806 ), VIP ( 192320 ), SCN2A, KCNQ2 ( 602235 ), NRXN1, and CHD7 ( 608892 ).
{PopulationInhabitants} Genetics
Smalley (1997) reported thatautismhas a {populationinhabitants} prevalence {of approximatelyof roughly} {4four} {to 5to five} in 10,000 with a male to {femalefeminine} ratio of {4four} to 1.
In a {reviewevaluateevaluationassessmentoverview} of 20 {studiesresearch} onautism{publishedrevealedprinted} between 1966 and 1997, Gillberg and Wing (1999) {determineddecided} thatautismis {considerablysignificantly} {moreextra} {commonwidespreadfrequent} than {previouslybeforehand} believed. The early {studiesresearch} yielded prevalence {ratescharges} of {underbeneathunderneathbelow} {0zero}.5 per 1,000 {childrenyoungsterskids}, whereas the later {studiesresearch} {showedconfirmed} a {meanimply} {ratepricefeecharge} of about 1 in 1,000. {ChildrenYoungstersKids} born after 1970 had a {mucha lot} {highergreaterlargerincreased} {ratepricefeecharge} than {thosethese} born {beforeearlier than} 1970.
Bertrand et al. (2001) {performedcarried out} a prevalence {studyresearchexamine} ofautismspectrum {disordersissuesproblems} in Brick Township, New Jersey. {There wereThere have been} 6.7 {casesinstancescircumstances} per 1,000 {childrenyoungsterskids}, aged {3three} to 10 years, in 1998. The prevalence {for childrenfor youngstersfor kids} whose {conditionsituation} met full diagnostic {criteriastandards} forautistic{disorderdysfunction} was {4four}.{0zero} {casesinstancescircumstances} per 1,000 {childrenyoungsterskids}, and the prevalence for PDD-not {otherwisein any other case} specified (NOS) and Asperger syndrome was 2.7 {casesinstancescircumstances} per 1,000 {childrenyoungsterskids}.
In a {reviewevaluateevaluationassessmentoverview}, Jones et al. (2008) {notedfamous} that {the significantthe numerous} {increaseimproveenhance} {in thewithin the} frequency with whichautismspectrum {disordersissuesproblems} is {diagnosedrecognizedidentified}, from {4four} per 10,000 in 1950 to {40forty} to 60 per 10,000 as of 2008, {resultsoutcomes} from {greaterhigherlargerbetter} {awarenessconsciousness}, availability of {servicesproviderscompanies}, and {changesmodificationsadjustments} in diagnostic {criteriastandards} {to includeto incorporate} a broader spectrum of neurodevelopmental {disordersissuesproblems}, {amongamongst} others.
Pathogenesis
Schain and Freedman (1961) reported elevated {levelsranges} of platelet serotonin (5-HT; see 182138 ) in {patientssufferers} withautism. Abramson et al. (1989) reported elevated blood serotonin inautisticprobands and {in theirof their} first-{degreediploma} {relativesrelationsfamily memberskinfolkkinfamily}. Piven et al. (1991) {founddiscovered} that serotonin {levelsranges} {werehave beenhad been} {significantlyconsiderably} {highergreaterlargerincreased} inautistic{individualspeople} with a sib withautismor PDD than in {thosethese} {without aand not using awith nowith out a} sib with these {disordersissuesproblems}, and thatautistic{patientssufferers} {withoutwith out} an affected sib had serotonin {levelsranges} that {werehave beenhad been} {significantlyconsiderably} {highergreaterlargerincreased} than controls.
A biologic {basisfoundation} ofautismwas {suggestedadvisedinstructedpromptrecommendedsteeredurged} by the {findingdiscovering} of developmental hypoplasia in lobules VI and VII of the cerebellar vermis ( Courchesne et al., 1988 ). The ontogenetically, developmentally, and anatomically distinct vermal lobules I to V {werehave beenhad been} {founddiscovered} to be of {normalregular} {sizemeasurementdimension}. {HoweverNeverthelessNonetheless}, Schaefer et al. (1996) disputed {the relationshipthe connection} of cerebellar vermal atrophy to {infantilechildish}autism. They {founddiscovered} that {the averagethe typicalthe common} relative {sizemeasurementdimension} of lobules VI and VII of the cerebellar vermis was no {differenttotally differentcompletely different} {in theirof their} {13thirteen} {patientssufferers} with {infantilechildish}autismwhen {compared toin comparison with} that of {125one hundred twenty fivea hundred twenty five} {normalregular} {individualspeople}. They {founddiscovered} relative hypoplasia of lobules VI and VII in {patientssufferers} with Rett syndrome ( 312750 ) and Sotos cerebral gigantism ( 117550 ), 2 {disordersissuesproblems} {characterizedcharacterised} byautisticbehaviors. No relative vermian atrophy was seen in {otherdifferent} {disordersissuesproblems} {associated withrelated to}autistic{behaviorconducthabits}: fragile X, Angelman (AS; 105830 ), {adultgrownup} phenylketonuria ( 261600 ), and Sanfilippo ( 252900 ). {FurthermoreMoreover}, they {founddiscovered} a relative atrophy of lobules VI and VII in {severala number of} {patientssufferers} with {primarymainmajor} cerebellar hypoplasia and Usher syndrome {typesortkind} II ( 276901 ), syndromes not {associated withrelated to}autistic{behaviorconducthabits}.
{AutopsyPost-mortem} and neuroimaging {studiesresearch} have {suggestedadvisedinstructedpromptrecommendedsteeredurged} thatautismspectrum {disorderdysfunction} is {causedtriggeredbrought onpromptedbrought aboutinducedprecipitated} {in partpartiallypartly} by {abnormalirregular} {brainmind} {developmentimprovementgrowth}. Benayed et al. (2005) reviewed cerebellar abnormalities inautismspectrum {disorderdysfunction}. The CNS {structureconstruction} most {consistentlypersistentlyconstantly} affected in {individualspeople} withautismis the cerebellum, with a {decreaselower} {in thewithin the} {number ofvariety of} Purkinje cells being {presentcurrent} in a majority. Neurodegenerative {signsindicators} are for {the mostprobably the mostessentially the most} {parthalf} absent from these {autopsypost-mortem} samples, suggesting a developmental defect. Neuroimaging {studiesresearch} have {consistentlypersistentlyconstantly} demonstrated posterior cerebellar hypoplasia. {AlthoughThough} the cerebellum has classically been {consideredthought-aboutthought of} a motor {controlmanagement} {centermiddleheart}, {functionalusefulpracticalpurposeful} imaging {studiesresearch} indicated that the cerebellum {is alsocan also becan be} {activelivelyenergetic} {duringthroughout} cognitive {tasksduties} {that arewhich arewhich might bewhich can be} {defectivefaulty} inautismspectrum {disordersissuesproblems}, {includingtogether with} language {and attentionand a spotlightand a focus}. Thus, the {identifiedrecognized} cerebellar defects {maymightcould} contribute {directly toon to} {some of thea few of thea number of theamong the} behavioral abnormalities {associated withrelated to}autismspectrum {disorderdysfunction}. In {turnflip}, genetic alterations that perturb cerebellar {developmentimprovementgrowth} {maymightcould} contribute to susceptibility toautismspectrum {disorderdysfunction}.
Regressiveautism, {characterizedcharacterised} most prominently by a {loss oflack of} language {skillsexpertiseabilities}, has been attributed to environmental {factorselementscomponents}, {particularlynotablysignificantly} {adverseantagonisticopposedhostileadversarial} reactions to vaccines; epidemiologic {evidenceproof}, {howeverneverthelessnonetheless}, {showsexhibitsreveals} no {associationaffiliation} between vaccination and {the ratethe speed} ofautismas reviewed by the Institute of {MedicineDrugsMedication} Immunization {SafetySecurity} {ReviewsCritiquesEvaluationsOpinions} (2001) ; see {alsoadditionally} Taylor et al. (2002) Lainhart et al. (2002) {notedfamous} that twin and {familyhousehold} {studiesresearch} {showedconfirmed} that the {liabilitylegal responsibility} toautismextends {beyondpast} {the fullthe completethe total}autismsyndrome and {includesconsists ofcontains} qualitatively {similarcomparablerelated}, albeit milder, deficits, {referred to asknown as} the broaderautismphenotype (BAP). If regressiveautismis solely {caused bybrought on byattributable to} environmental {eventsoccasions}, {such assimilar tocorresponding tocomparable toakin toreminiscent ofresemblingequivalent to} {adverseantagonisticopposedhostileadversarial} reactions to vaccines, {ratescharges} of the BAP {in thewithin the} {relativesrelationsfamily memberskinfolkkinfamily} {of childrenof youngstersof kids} with regressiveautism{should beought to bemust beneeds to be} no {greaterhigherlargerbetter} than {in thewithin the} {generalcommonbasicnormal} {populationinhabitants}. If environmental {eventsoccasions} {do notdon’t} independently {causetrigger} regressiveautism, or {if theyin the event that they} act as ‘second-hit’ phenomena in {childrenyoungsterskids} who {already havehave already got} a genetic {liabilitylegal responsibility} toautism, {ratescharges} of the BAP {should beought to bemust beneeds to be} {similarcomparablerelated} in {relativesrelationsfamily memberskinfolkkinfamily} ofautistic{childrenyoungsterskids} with and {withoutwith out} regression. Lainhart et al. (2002) {founddiscovered} that {the ratethe speed} of the BAP was {significantlyconsiderably} {highergreaterlargerincreased} in {parentsmother and fatherdad and mom} {of childrenof youngstersof kids} with regressive and nonregressiveautismthan in {parentsmother and fatherdad and mom} of nonautistic {childrenyoungsterskids}. They concluded that environmental {eventsoccasions} are unlikely to be {the solethe onlythe only real} {cause ofexplanation forreason forreason behind} regressiveautism, {althoughthough} environmental {eventsoccasions} {maymightcould} act in an additive or ‘second-hit’ {fashionstyletrendvogue} in {individualspeople} with a genetic vulnerability toautism.
In a {reviewevaluateevaluationassessmentoverview}, Jones et al. (2008) {discussedmentioned} the {hypothesisspeculation} that dysregulation of methylation of {brainmind}-expressed genes on the X chromosome constitutes {the majorthe mainthe most importantthe keythe foremost} predisposition to {the developmentthe event} ofautismspectrum {disordersissuesproblems}. Broad {evidenceproof} {consistent withaccording toin keeping within line within step withper} this epigenetic {effectimpact} {includesconsists ofcontains} marked {excessextra} of males {amongamongst} {individualspeople} affected with ASD, most {patientssufferers} have a sporadic {occurrenceprevalenceincidence} of the {disorderdysfunction}, and most {patientssufferers} {do not havedon’t havewouldn’t haveshouldn’t haveshould not havewould not havedo not need} syndromic {featuresoptions}.
In {studiesresearch} of lymphocytes from 10 {childrenyoungsterskids} withautismand 10 controls, Giulivi et al. (2010) {founddiscovered} that {patientssufferers} withautism{werehave beenhad been} {moreextra} {likely tomore likely toprone to} have mitochondrial dysfunction, mtDNA overreplication, and mtDNA deletions {compared toin comparison with} {normallyusually} {developingcreatinggrowing} {childrenyoungsterskids}. Lymphocytes from {childrenyoungsterskids} withautismhad {lowerdecrease} mitochondrial-dependent oxygen consumption, with low {complexcomplicatedadvanced} I (6 of 10) {and complexand sophisticatedand complicated} V ({4four} of 10) {activityexercise}.Autistic{childrenyoungsterskids} had {increasedelevated} plasma pyruvate {levelsranges} and {increasedelevated} lymphocyte hydrogen peroxide {productionmanufacturing}. {Five5}autistic{patientssufferers} {and 2and a couple ofand a pair of} controls had mtDNA overreplication, {and 2and a couple ofand a pair of} {patientssufferers} and no controls had mtDNA deletion. {OverallGeneralTotal}, the findings {suggestedadvisedinstructedpromptrecommendedsteeredurged} thatautism{may becould also be} {associated withrelated to} mitochondrial dysfunction, {which maywhich can} {reflectmirrorreplicate} {insufficientinadequate} {energypowervitality} {productionmanufacturing}. {HoweverNeverthelessNonetheless}, Giulivi et al. (2010) {notedfamous} that the observations {did notdidn’t} elucidate {primarymainmajor} or secondary {effectsresults}.
Castermans et al. (2010) described the positional cloning of SCAMP5 ( 613766 ) as a candidate gene forautism, {basedbased mostlyprimarily based} on {findingdiscovering} a de novo chromosomal translocation t1;15(p36.{11eleven};q24.2) in a {40forty}-{yearyr12 months}-{oldpreviousoutdated} affected male. SCAMP5, which was silenced on the {derivativeby-productspinoff} chromosome, encodes a {brainmind}-enriched protein {involvedconcerned} in membrane trafficking, {similar tojust likemuch like} the {previouslybeforehand} {identifiedrecognized} candidate genes NBEA ( 604889 ) and AMISYN (STXBP6; 607958 ). Gene silencing of Nbea, Amisyn, and Scamp5 in mouse beta-TC3 cells resulted in a 2-fold {increaseimproveenhance} in stimulated secretion {of largeof hugeof enormous} dense-core vesicles (LDCVs), whereas overexpression suppressed secretion. Ultrastructural {analysisevaluation} of blood platelets fromautismpatients with haploinsufficiency of 1 of {the 3the three} candidate genes {showedconfirmed} morphologic abnormalities of dense-core granules, which {closelyintentlycarefully} resembled LDCVs. Castermans et al. (2010 ) {suggestedadvisedinstructedpromptrecommendedsteeredurged} that in a subgroup of {patientssufferers}, the regulation of neuronal vesicle trafficking {may becould also be} {involvedconcerned} {in thewithin the} pathogenesis ofautism.
Voineagu et al. (2011) analyzed postmortem {brainmind} tissue samples from 19autism{casesinstancescircumstances} and 17 controls from theAutismTissue {ProjectVentureChallengeUndertakingMission} and the Harvard {brainmind} {bankfinancial institution} {usingutilizing} Illumina microarrays. For {eachevery} {individualparticular person}, they profiled {3three} {regionsareas} {previouslybeforehand} implicated inautism: superior temporal gyrus, prefrontal cortex, and cerebellar vermis. Voineagu et al. (2011) demonstrated {consistentconstant} {differencesvariations} in transcriptome {organizationgroup} betweenautisticand {normalregular} {brainmind} by gene coexpression {networkcommunity} {analysisevaluation}. Remarkably, regional patterns of gene expression that {typicallysometimesusually} distinguish frontal and temporal cortex are {significantlyconsiderably} attenuated {in thewithin the}autismspectrum {disorderdysfunction} (ASD) {brainmind}, suggesting abnormalities in cortical patterning. Voineagu et al. (2011) {furtheradditional} {identifiedrecognized} discrete modules of coexpressed genes {associated withrelated to}autism: a neuronal module enriched for {knownrecognizedidentified}autismsusceptibility genes, {includingtogether with} the neuronal-{specificparticular} splicing {factorissue} A2BP1 ({also known asalso calledalso referred to asoften known as} FOX1, 605104 ), and a module enriched for immune genes and glial markers. {UsingUtilizing} {highexcessive}-throughput RNA sequencing, they demonstrated dysregulated splicing of A2BP1-dependent {alternativevariousdifferent} exons {in thewithin the} ASD {brainmind}. {MoreoverFurthermore}, {usingutilizing} {a publisheda printeda broadcast}autismgenomewide {associationaffiliation} {studyresearchexamine} (GWAS) {dataknowledgeinformation} set, Voineagu et al. (2011) {showedconfirmed} that the neuronal module is enriched for genetically {associatedrelated} variants, {providingoffering} {independentunbiasedimpartial} {supporthelpassist} for the causal involvement of {thosethese} genes inautism. {The topThe highest} module for differential expression betweenautism{controlmanagement} {groupsteams} was {highlyextremely} enriched for neuronal markers. The hubs of this group, {calledreferred to asknown as} M12 {in thison this} {studyresearchexamine}, which represented the genes with {the highestthe very bestthe best} rank of M12 membership, {werehave beenhad been} A2BP1 {but alsobut in additionbut additionally} APBA2 ( 602712 ), SCAMP5 ( 613766 ), CNTNAP1 ( 602346 ), KLC2 ( 611729 ), and CHRM1 ( 118510 ). In {contrastdistinction}, the immune-glial module {showedconfirmed} no enrichment forautismGWAS {signalsalertsindicators}, indicating a nongenetic etiology for this {processcourse of}. Voineagu et al. (2011) concluded that their {resultsoutcomes} {providedofferedsupplied} {strongrobuststurdy} {evidenceproof} for convergent molecular abnormalities in ASD, and implicated transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction {in thison this} {disorderdysfunction}.
Gilman et al. (2011) developed a {networkcommunity}-{basedbased mostlyprimarily based} {analysisevaluation} of genetic associations (NETBAG) and used this to {identifydetermineestablish} {a largea big} biologic {networkcommunity} of genes affected by {rareuncommon} de novo CNVs inautism. The genes forming the {networkcommunity} are primarily {relatedassociated} to synapse {developmentimprovementgrowth}, axon {targetingconcentrating onfocusing on}, and neuron motility. The {identifiedrecognized} {networkcommunity} was strongly {relatedassociated} to genes {previouslybeforehand} implicated inautismand {intellectualmental} {disabilityincapacity} phenotypes. Gilman et al. (2011) {suggestedadvisedinstructedpromptrecommendedsteeredurged} that their {resultsoutcomes} {werehave beenhad been} {alsoadditionally} {consistent withaccording toin keeping within line within step withper} the {hypothesisspeculation} that {significantlyconsiderably} stronger {functionalusefulpracticalpurposeful} perturbations are required to {triggerset off} theautisticphenotype in females {compared toin comparison with} males. {OverallGeneralTotal}, the {presentedintroducedoffered} {analysisevaluation} of de novo variants supported the {hypothesisspeculation} that perturbed synaptogenesis is {at theon the} {heartcoronary heart} ofautism. {MoreExtra} {generallyusuallytypically}, their {studyresearchexamine} {providedofferedsupplied} proof of the {principleprecept} that networks underlying {complexcomplicatedadvanced} human phenotypes {can becould bemay bemight bewill be} {identifiedrecognized} by a {networkcommunity}-{basedbased mostlyprimarily based} {functionalusefulpracticalpurposeful} {analysisevaluation} of {rareuncommon} genetic variants.
{To studyTo reviewTo check} genomewide mutation {ratescharges}, Kong et al. (2012) sequenced {the entirethe wholethe completeall theyour completeyour entire} genomes of {78seventy eight} Icelandic {parentmother or fatherfather or motherdad or mummum or dadguardian}-offspring trios at {highexcessive} {coverageprotection}. Forty-{four4} of the probands hadautisticspectrum {disorderdysfunction} and 21 {werehave beenhad been} schizophrenic ( 181500 ). Kong et al. (2012) {founddiscovered} that, with {an averagea meana median} father’s age of 29.7, {the averagethe typicalthe common} de novo mutation {ratepricefeecharge} is 1.20 x 10(-{8eight}) per nucleotide per {generationeratechnology}. Most notably, {the diversitythe rangethe variety} in mutation {ratepricefeecharge} of single-nucleotide polymorphisms was dominated by the age of {the fatherthe daddy} at conception of {the childthe kid}. The {effectimpact} {is an increaseis a rise} of about 2 mutations per {yearyr12 months}. An exponential {modelmannequin} estimates paternal mutations doubling {everyeach} {16sixteen}.5 years. After accounting for random Poisson variation, father’s age is estimated {to explainto elucidateto clarify} {nearlyalmostpractically} {all of theall thethe entire} remaining variation {in thewithin the} de novo mutation counts. Kong et al. (2012) {statedsaidacknowledged} that there had been a {recentcurrentlatest} transition of Icelanders from a rural agricultural to an {urbancity} industrial {way of lifelifestyle}, which engendered a {rapidspeedyfast} and sequential drop {in thewithin the} {averagecommon} age of fathers at conception from 34.9 years in 1900 to 27.9 years in 1980, {followedadopted} by an equally swift climb {backagain} to 33.{0zero} years in 2011, primarily owing to the {effectimpact} {of higherof upper} {educationschoolingtraining} and the {increasedelevated} use of contraception. On {the basisthe ideathe premise} of the fitted linear {modelmannequin}, whereas {individualspeople} born in 1900 carried on {averagecommon} {73seventy three}.7 de novo mutations, {thosethese} born in 1980 carried on {averagecommon} {onlysolely} {59fifty nine}.7 such mutations (a {decreaselower} of 19.1%), and the mutational load {of individualsof people} born in 2011 had {increasedelevated} by 17.2% to {69sixty nine}.9. Kong et al. (2012) concluded that their observations {shed light onmake clear} the {importancesignificance} of {the fatherthe daddy}’s age on {the riskthe dangerthe chance} of {diseasesillnessesailments} {such assimilar tocorresponding tocomparable toakin toreminiscent ofresemblingequivalent to} schizophrenia andautism.
King et al. (2013) {founddiscovered} that topotecan, a topoisomerase-1 (TOP1; 126420 ) inhibitor, dose-dependently reduces the expression of {extremelyextraordinarily} {longlengthy} genes in mouse and human neurons, {includingtogether with} {nearlyalmostpractically} all genes {that arewhich arewhich might bewhich can be} longer than 200 kb. Expression of {longlengthy} genes {is alsocan also becan be} {reducedlowereddecreaseddiminished} after knockdown of Top1 or Top2b ( 126431 ) in neurons, highlighting that {botheach} enzymes are required for full expression of {longlengthy} genes. By mapping RNA polymerase II density genomewide in neurons, King et al. (2013) {founddiscovered} that this {lengthsize}-dependent {effectimpact} on gene expression was {due tobecause ofas a result ofresulting fromon account ofas a consequence ofattributable to} impaired transcription elongation. {InterestinglyApparentlyCuriously}, many {highexcessive}-confidenceautismspectrum {disorderdysfunction} candidate genes are exceptionally {longlengthy} and {werehave beenhad been} {reducedlowereddecreaseddiminished} in expression after TOP1 inhibition. King et al. (2013) concluded that {chemicalschemical compoundschemical substances} and genetic mutations that impair topoisomerases {couldmightmay} {commonlygenerally} contribute toautismspectrum {disordersissuesproblems} and {otherdifferent} neurodevelopmental {disordersissuesproblems}.
Gamsiz et al. (2013) {conductedcarried outperformed} a genomewide {analysisevaluation} of runs of homozygosity (ROH) in simplex ASD-affected {familieshouseholds} consisting of a proband {diagnosedrecognizedidentified} with ASD and {at leasta minimum ofno less thanat the leastat the very leastnot less than} 1 unaffected sib. In these {familieshouseholds}, probands with an IQ of 70 or {belowunderbeneath} {showpresent} {moreextra} ROH than their unaffected sibs, whereas probands with an IQ {greaterhigherlargerbetter} than 70 {do notdon’t} {showpresent} this {excessextra}. {AlthoughThough} ASD {is faris wayis much} {moreextra} {commonwidespreadfrequent} in males than in females, the proportion of females {increaseswill increase} with {decreasingreducinglowering} IQ. Gamsiz et al. (2013) {statedsaidacknowledged} that their {dataknowledgeinformation} supported an {associationaffiliation} between ROH burden andautismdiagnosis in {girlswomenladies}; {howeverneverthelessnonetheless}, they {were notweren’t} {able tocapable ofin a position to} {showpresent} that this {effectimpact} was {independentunbiasedimpartial} of low IQ. The authors {alsoadditionally} {identifiedrecognized} {severala number of}autismcandidate genes on {the basisthe ideathe premise} of their being {eitherboth} a single gene {that isthat’s} {withininside} an ROH interval {and that isand that’s} recurrent inautism, or a gene {that isthat’s} {withininside} an ROH block and that harbors a homozygous {rareuncommon} deleterious variant upon {analysisevaluation} of exome sequencing {dataknowledgeinformation}.
Animal {ModelMannequin}
Tabuchi et al. (2007) {introducedlaunched} the R451C (arg451 to cys; 300336.0001 ) substitution in neuroligin-{3three} into mice. R451C mutant mice {showedconfirmed} impaired social interactions {buthowever} enhanced spatial {learningstudying} {abilitiestalentsskills}. Unexpectedly these behavioral {changesmodificationsadjustments} {werehave beenhad been} accompanied by {an increasea rise} in inhibitory synaptic transmission with no {apparentobvious} {effectimpact} on excitatory synapses. Deletion of neuroligin-{3three}, in {contrastdistinction}, {did notdidn’t} {causetrigger} such {changesmodificationsadjustments}, indicating that the R451C substitution represents a {gainachieveacquire}-of-{functionperformoperate} mutation. Tabuchi et al. (2007) concluded that {increasedelevated} inhibitory synaptic transmission {maymightcould} contribute to humanautismspectrum {disordersissuesproblems} and that the R451C knockin mice {may becould also be} a {usefulhelpful} {modelmannequin} for {studyinglearningfinding out}autism-{relatedassociated} behaviors.
{HistoryHistorical past}
Eisenberg (1994) {providedofferedsupplied} a biographic sketch of Leo Kanner (1894-1981), the pioneer pediatric psychiatrist who first described and named {infantilechildish}autism( Kanner, 1943 ).
REFERENCES
1.
Abramson, R. {KOkayOk}., Wright, H. H., Carpenter, R., Brennan, W., Lumpuy,, Cole, E., {YoungYounger}, S. R.Elevated blood serotonin inautisticprobands and their first-{degreediploma} {relativesrelationsfamily memberskinfolkkinfamily}.J.AutismDev. Disord. 19: 397-407, 1989.PubMed: 2793785 , {relatedassociated} citations
2.
Alarcon, M., Cantor, R. M., Liu, J., Gilliam, T. C.,AutismGenetic {ResourceUseful resource} {ExchangeTradeChangeAlternate} Consortium, Geschwind, D. H.{EvidenceProof} for a language quantitative trait locus on chromosome 7q in multiplexautism{familieshouseholds}.Am. J. Hum. Genet. 70: 60-{71seventy one}, 2002.PubMed: 11741194 , {relatedassociated} citations Full {TextTextual content}: Elsevier Science
{3three}.
Publicado por