| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Research Abstract |
Schizophrenia has a relatively strong genetic background(λs=10). Because of the typically adolescent onset and the loss of sociality in patients, schizophrenia susceptibility alleles are expected to be selected out through generations. However, the prevalence is stably high at~ 1% in any of the populations surveyed. To explain the paradox, I hypothesized that the schizophrenia susceptibility alleles are maintained by the non-neutral process such as balancing selection. To test this hypothesis, I sequenced six schizophrenia susceptibility genes, BDNF, SLC18A1, COMT, DRD1, DRD2, DRD4 from 72 unrelated humans(24 Caucasians, 24 African Ameericans and 24 Japanese) and 24 unrelated chimpanzees as non-human controls. Using the variation data set, I examined neutrality by the summary statistics approach such as Tajima' s method. I identified a significant signal of balancing selection in the regions of coding SNPs in DRD2(rs6275, rs6277) and in COMT(rs4680). All of these SNPs a significant association has been frequently reported with schizophrenia. By coalescent simulation I dated the haplotypes in the selected regions in both genes to be> 1 MYA. I conclude that some of the schizophrenia susceptible alleles have been maintained by balancing selection of which the target may be the phenotypes related to schizophrenia as well as human brain functions.
|
