title: Evaluating mitochondrial DNA variation in autism spectrum disorders.
abstract: Despite the increasing speculation that oxidative stress and abnormal energy metabolism may play a role in Autism Spectrum Disorders (ASD), and the observation that patients with mitochondrial defects have symptoms consistent with ASD, there are no comprehensive published studies examining the role of mitochondrial variation in autism. Therefore, we have sought to comprehensively examine the role of mitochondrial DNA (mtDNA) variation with regard to ASD risk, employing a multi-phase approach. In phase 1 of our experiment, we examined 132 mtDNA single-nucleotide polymorphisms (SNPs) genotyped as part of our genome-wide association studies of ASD. In phase 2 we genotyped the major European mitochondrial haplogroup-defining variants within an expanded set of autism probands and controls. Finally in phase 3, we resequenced the entire mtDNA in a subset of our Caucasian samples (∼400 proband-father pairs). In each phase we tested whether mitochondrial variation showed evidence of association to ASD. Despite a thorough interrogation of mtDNA variation, we found no evidence to suggest a major role for mtDNA variation in ASD susceptibility. Accordingly, while there may be attractive biological hints suggesting the role of mitochondria in ASD our data indicate that mtDNA variation is not a major contributing factor to the development of ASD.
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Athena
authors.initials: A
authors.lastname: Hadjixenofontos
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schmidt
authors.forename: Patrice L
authors.initials: PL
authors.lastname: Whitehead
authors.forename: Ioanna
authors.initials: I
authors.lastname: Konidari
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Hedges
authors.forename: Harry H
authors.initials: HH
authors.lastname: Wright
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Abramson
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Menon
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cuccaro
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: John R
authors.initials: JR
authors.lastname: Gilbert
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Eden R
authors.initials: ER
authors.lastname: Martin
authors.forename: Jacob L
authors.initials: JL
authors.lastname: McCauley
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial