Mutation screening and transmission disequilibrium study of ATP10C in autism.
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.
Kim
Soo-Jeong
SJ
Laboratory of Developmental Neuroscience, Child and Adolescent Psychiatry, Department of Psychiatry MC3077, University of Chicago, Chicago, Illinois 60637, USA.
Herzing
Laura B K
LB
Veenstra-VanderWeele
Jeremy
J
Lord
Catherine
C
Courchesne
Rachel
R
Leventhal
Bennett L
BL
Ledbetter
David H
DH
Courchesne
Eric
E
Cook
Edwin H
EH
D000251:Adenosine Triphosphatases / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D004247:DNA; D000251:Adenosine Triphosphatases; C426648:ATP10A protein, human