Mutation screening and transmission disequilibrium study of ATP10C in autism

• Published in: American journal of medical genetics Vol. 114; no. 2; pp. 137 - 143
• Main Authors: Kim, Soo-Jeong, Herzing, Laura B.K., Veenstra-VanderWeele, Jeremy, Lord, Catherine, Courchesne, Rachel, Leventhal, Bennett L., Ledbetter, David H., Courchesne, Eric, Cook Jr, Edwin H.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 08-03-2002; Wiley-Liss
• Subjects: 15q11-q13; Adenosine Triphosphatases - genetics; association; ATP10C; ATPIOC; autism; Autistic Disorder - genetics; Biological and medical sciences; Carrier Proteins - genetics; Child; Child, Preschool; D15S1534; D15S1535; DNA - chemistry; DNA - genetics; DNA Mutational Analysis; Female; General aspects. Genetic counseling; Genotype; Humans; Infant; Linkage Disequilibrium; Male; Medical genetics; Medical sciences; Membrane Transport Proteins; Mutation; polymorphism; Polymorphism, Single Nucleotide; Human; Cartography; Transmission; Chromosome; Developmental disorder; Medical screening; Protein; Characterization; Interest; Autism; Screening; Gene; Mother; Distal; Distribution; Genetics; Region; Mutation; Cell; Polymorphism
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/ajmg.10238

Autism is a complex genetic disorder. Chromosome 15 is of particular interest in this disorder, because of previous reports of individuals with autism with chromosomal abnormalities in the 15q11‐q13 region. Transmission disequilibrium between polymorphisms in this region and autism has been also been reported in some, but not all studies. Recently, a novel maternally expressed gene, ATP10C, was characterized and mapped to the chromosome 15q11‐q13 region, 200 kb distal to UBE3A. It encodes a putative aminophospholipid translocase likely to be involved in the asymmetric distribution of proteins in the cell membrane. Preferential maternal expression has been demonstrated in fibroblasts and brain. Because of its physical location and imprinting pattern, ATP10C was considered to be a candidate gene for chromosome 15‐associated autism. In an effort to find the genes responsible for autism in this chromosomal region, 1.5 kb of the 5′ flanking region, as well as the coding and splicing regions of ATP10C, were screened for sequence variants. Several polymorphic markers including five nonsynonymous SNPs were identified. To investigate transmission disequilibrium between ATP10C and autism, a family‐based association study was conducted for 14 markers in 115 autism trios. No significant transmission disequilibrium was found, suggesting ATP10C is unlikely to contribute strongly to susceptibility to autism in these families. However, due to limited power to detect genes of modest effect, the possible functional role of the nonsynonymous SNPs and the functional implications of the SNPs identified from 5′ flanking region and intron 2 splicing region may be evaluated in further studies. © 2002 Wiley‐Liss, Inc.