Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders

Christian P. Schaaf, Aniko Sabo, Yasunari Sakai, Jacy Crosby, Donna Muzny, Alicia Hawes, Lora Lewis, Humeira Akbar, Robin Varghese, Eric Boerwinkle, Richard A. Gibbs, Huda Y. Zoghbi

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numberddr243
Pages (from-to)3366-3375
Number of pages10
JournalHuman Molecular Genetics
Volume20
Issue number17
DOIs
Publication statusPublished - Sep 1 2011
Externally publishedYes

Fingerprint

Autistic Disorder
Gene Dosage
Genes
Technology
Mutation
Population
Autism Spectrum Disorder

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Schaaf, C. P., Sabo, A., Sakai, Y., Crosby, J., Muzny, D., Hawes, A., ... Zoghbi, H. Y. (2011). Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders. Human Molecular Genetics, 20(17), 3366-3375. [ddr243]. https://doi.org/10.1093/hmg/ddr243

Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders. / Schaaf, Christian P.; Sabo, Aniko; Sakai, Yasunari; Crosby, Jacy; Muzny, Donna; Hawes, Alicia; Lewis, Lora; Akbar, Humeira; Varghese, Robin; Boerwinkle, Eric; Gibbs, Richard A.; Zoghbi, Huda Y.

In: Human Molecular Genetics, Vol. 20, No. 17, ddr243, 01.09.2011, p. 3366-3375.

Research output: Contribution to journalArticle

Schaaf, CP, Sabo, A, Sakai, Y, Crosby, J, Muzny, D, Hawes, A, Lewis, L, Akbar, H, Varghese, R, Boerwinkle, E, Gibbs, RA & Zoghbi, HY 2011, 'Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders', Human Molecular Genetics, vol. 20, no. 17, ddr243, pp. 3366-3375. https://doi.org/10.1093/hmg/ddr243
Schaaf, Christian P. ; Sabo, Aniko ; Sakai, Yasunari ; Crosby, Jacy ; Muzny, Donna ; Hawes, Alicia ; Lewis, Lora ; Akbar, Humeira ; Varghese, Robin ; Boerwinkle, Eric ; Gibbs, Richard A. ; Zoghbi, Huda Y. / Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders. In: Human Molecular Genetics. 2011 ; Vol. 20, No. 17. pp. 3366-3375.
@article{175b837a2c1a4c6db527739867dd6002,
title = "Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders",
abstract = "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.",
author = "Schaaf, {Christian P.} and Aniko Sabo and Yasunari Sakai and Jacy Crosby and Donna Muzny and Alicia Hawes and Lora Lewis and Humeira Akbar and Robin Varghese and Eric Boerwinkle and Gibbs, {Richard A.} and Zoghbi, {Huda Y.}",
year = "2011",
month = "9",
day = "1",
doi = "10.1093/hmg/ddr243",
language = "English",
volume = "20",
pages = "3366--3375",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "17",

}

TY - JOUR

T1 - Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders

AU - Schaaf, Christian P.

AU - Sabo, Aniko

AU - Sakai, Yasunari

AU - Crosby, Jacy

AU - Muzny, Donna

AU - Hawes, Alicia

AU - Lewis, Lora

AU - Akbar, Humeira

AU - Varghese, Robin

AU - Boerwinkle, Eric

AU - Gibbs, Richard A.

AU - Zoghbi, Huda Y.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80051674258&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051674258&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddr243

DO - 10.1093/hmg/ddr243

M3 - Article

C2 - 21624971

AN - SCOPUS:80051674258

VL - 20

SP - 3366

EP - 3375

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 17

M1 - ddr243

ER -