Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders

被引：116

作者：

Schaaf, Christian P. ^{[1
]}

Sabo, Aniko ^{[2
]}

Sakai, Yasunari ^{[1
,5
]}

Crosby, Jacy ^{[6
]}

Muzny, Donna ^{[2
]}

Hawes, Alicia ^{[2
]}

Lewis, Lora ^{[2
]}

Akbar, Humeira ^{[2
]}

Varghese, Robin

Boerwinkle, Eric ^{[6
]}

Gibbs, Richard A. ^{[1
,2
]}

Zoghbi, Huda Y. ^{[1
,3
,4
,5
,7
]}

机构：

[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[2] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Pediat, Program Dev Biol, Houston, TX 77030 USA

[4] Baylor Coll Med, Dept Neurosci, Program Dev Biol, Houston, TX 77030 USA

[5] Howard Hughes Med Inst, Chevy Chase, MD USA

[6] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA

[7] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA

来源：

HUMAN MOLECULAR GENETICS | 2011年 / 20卷 / 17期

关键词：

COPY NUMBER VARIATION; MENTAL-RETARDATION; ALLELIC VARIANTS; GENE; ASSOCIATION; MUTATIONS; HOXA1; FOXP2; SUSCEPTIBILITY; HOXB1;

D O I：

10.1093/hmg/ddr243

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Autism spectrum disorders (ASDs) are a heterogeneous group of neuro-developmental disorders. While significant progress has been made in the identification of genes and copy number variants associated with syndromic autism, little is known to date about the etiology of idiopathic non-syndromic autism. Sanger sequencing of 21 known autism susceptibility genes in 339 individuals with high-functioning, idiopathic ASD revealed de novo mutations in at least one of these genes in 6 of 339 probands (1.8%). Additionally, multiple events of oligogenic heterozygosity were seen, affecting 23 of 339 probands (6.8%). Screening of a control population for novel coding variants in CACNA1C, CDKL5, HOXA1, SHANK3, TSC1, TSC2 and UBE3A by the same sequencing technology revealed that controls were carriers of oligogenic heterozygous events at significantly (P < 0.01) lower rate, suggesting oligogenic heterozygosity as a new potential mechanism in the pathogenesis of ASDs.

引用

页码：3366 / 3375

页数：10

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