title: Using extended pedigrees to identify novel autism spectrum disorder (ASD) candidate genes.
abstract: 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.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Chedoke Campus (Evel Building, Room 457), Hamilton, ON, Canada, woodbur@mcmaster.ca.
authors.forename: Marc
authors.initials: M
authors.lastname: Woodbury-Smith
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.forename: Bhooma
authors.initials: B
authors.lastname: Thiruvahindrapduram
authors.forename: Anath C
authors.initials: AC
authors.lastname: Lionel
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.forename: Daniele
authors.initials: D
authors.lastname: Merico
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Fernandez
authors.forename: Eric
authors.initials: E
authors.lastname: Duku
authors.forename: James S
authors.initials: JS
authors.lastname: Sutcliffe
authors.forename: Irene
authors.initials: I
authors.lastname: O'Conner
authors.forename: Christina
authors.initials: C
authors.lastname: Chrysler
authors.forename: Ann
authors.initials: A
authors.lastname: Thompson
authors.forename: Barbara
authors.initials: B
authors.lastname: Kellam
authors.forename: Kristiina
authors.initials: K
authors.lastname: Tammimies
authors.forename: Susan
authors.initials: S
authors.lastname: Walker
authors.forename: Ryan K C
authors.initials: RK
authors.lastname: Yuen
authors.forename: Mohammed
authors.initials: M
authors.lastname: Uddin
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Howe
authors.forename: Morgan
authors.initials: M
authors.lastname: Parlier
authors.forename: Kathy
authors.initials: K
authors.lastname: Whitten
authors.forename: Peter
authors.initials: P
authors.lastname: Szatmari
authors.forename: Veronica J
authors.initials: VJ
authors.lastname: Vieland
authors.forename: Joseph
authors.initials: J
authors.lastname: Piven
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D030561:Databases, Nucleic Acid; D066264:Datasets as Topic; D042967:Electron Transport Complex I; D005260:Female; D020440:Gene Duplication; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D009245:NADH Dehydrogenase / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance
chemical_list: C112232:NDUFV1 protein, human; D009245:NADH Dehydrogenase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D042967:Electron Transport Complex I