Association study of the commonly recognized breakpoints in chromosome 15q11-q13 in Japanese autistic patients.
OBJECTIVE
Chromosome 15q11-q13 has been proposed to harbor a gene for autism susceptibility because deletions of the region lead to Prader-Willi syndrome and Angelman syndrome, whose phenotypes overlap with autism. These deletions generally occur with the use of three commonly recognized breakpoints (BP1, BP2, and BP3); therefore, it may be possible that genes located in the breakpoints are impaired and contribute to autism susceptibility. No study, however, has investigated the genetic association between the breakpoints and autism, to our knowledge. Here, we investigated the association between the common breakpoints of chromosome 15q11-q13 and autism in a Japanese population.


METHODS
We genotyped 12 single nucleotide polymorphisms (SNPs) in 166 patients with autistic disorder and 415 healthy controls. The SNPs are located in two additional distal breakpoints (BP4 and BP5), involved in duplications and triplications of the region, as well as in BP1 and BP3.


RESULTS
No significant difference was observed between the controls and patients in allelic frequencies or genotypic distributions of the 12 SNPs. In the analyses of the suggested five haplotypes, no significant difference between the controls and patients was observed in the distributions of any estimated haplotypes. When confining the patients to only males, a difference was observed in a two-marker haplotype in BP3 between the controls and patients (global permutation P value=0.006), although the statistical level became insignificant after correction for multiple testing.


CONCLUSIONS
This study provides no positive evidence of the association between the common breakpoints of chromosome 15q11-q13 and autism in the Japanese population.
Kato
Chieko
C
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Tochigi
Mamoru
M
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
D000328:Adult; D044466:Asian People / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D019457:Chromosome Breakage; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D051859:Neuroendocrine Secretory Protein 7B2 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
C491636:APBA2 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; C497678:SCG5 protein, human