Using extended pedigrees to identify novel autism spectrum disorder (ASD) candidate genes

作者：Woodbury Smith Marc^*; Paterson Andrew D; Thiruvahindrapduram Bhooma; Lionel Anath C; Marshall Christian R; Merico Daniele; Fernandez Bridget A; Duku Eric; Sutcliffe James S; O'Conner Irene; Chrysler Christina; Thompson Ann; Kellam Barbara; Tammimies Kristiina; Walker Susan; Yuen Ryan K C; Uddin Mohammed; Howe Jennifer L; Parlier Morgan; Whitten Kathy; Szatmari Peter; Vieland Veronica J; Piven Joseph; Scherer Stephen W

来源：Human Genetics, 2015, 134(2): 191-201.

DOI：10.1007/s00439-014-1513-6

Copy number variation has emerged as an important cause of phenotypic variation, particularly in relation to some complex disorders. Autism spectrum disorder (ASD) is one such disorder, in which evidence is emerging for an etiological role for some rare penetrant de novo and rare inherited copy number variants (CNVs). De novo variation, however, does not always explain the familial nature of ASD, leaving a gap in our knowledge concerning the heritable genetic causes of this disorder. Extended pedigrees, in which several members have ASD, provide an opportunity to investigate inherited genetic risk factors. In this current study, we recruited 19 extended ASD pedigrees, and, using the Illumina HumanOmni2.5 BeadChip, conducted genome-wide CNV interrogation. We found no definitive evidence of an etiological role for segregating CNVs in these pedigrees, and no evidence that linkage signals in these pedigrees are explained by segregating CNVs. However, a small number of putative de novo variants were transmitted from BAP parents to their ASD offspring, and evidence emerged for a rare duplication CNV at 11p13.3 harboring two putative 'developmental/neuropsychiatric' susceptibility gene(s), GSTP1 and NDUFV1.

• 出版日期2015-2