Association study of the 15q11-q13 maternal expression domain in Japanese autistic patients.
Chromosome 15q11-q13 has been a focus of genetic studies of autism susceptibility, because cytogenetic abnormalities are frequently observed in this region in autistic patients. An imprinted, maternally expressed gene within the region may have a role in autistic symptomatology. In the present study, we investigated the association between autism and the maternal expression domain (MED) in the region, containing the UBE3A and ATP10C genes, and the upstream imprinting center (IC), which mediates coordinate control of imprinted expression throughout the region. We analyzed 41 single nucleotide polymorphisms (SNPs) in 166 patients with autism and 416 controls from a Japanese population. As a result, a statistically significant difference after correction for multiple testing was observed between the patients and controls in the genotypic distribution of SNP rs7164989 (SNP8 in this study) located in SNRPN, whose promoter corresponds to the IC (P = 0.018, corrected for multiple testing). In the analysis of a four-marker haplotype located in ATP10C, a statistically significant difference after correction for multiple testing was observed in the frequency of one haplotype between male patients and controls (permutation P = 0.033, corrected for multiple testing). Thus, the present study may suggest the association between autism and the MED or the upstream IC in chromosome 15q11-q13 in the Japanese population.
Kato
Chieko
C
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Bunkyo, Tokyo, Japan.
Tochigi
Mamoru
M
Ohashi
Jun
J
Koishi
Shinko
S
Kawakubo
Yuki
Y
Yamamoto
Kenji
K
Matsumoto
Hideo
H
Hashimoto
Ohiko
O
Kim
Soo-Yung
SY
Watanabe
Keiichiro
K
Kano
Yukiko
Y
Nanba
Eiji
E
Kato
Nobumasa
N
Sasaki
Tsukasa
T
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D001321:Autistic Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009035:Mothers; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors
D026901:Membrane Transport Proteins; D000251:Adenosine Triphosphatases; C426648:ATP10A protein, human