Study on susceptibly genes for schizophrenia and tubercubsis

1. 精神分裂症易感性的研究首次全基因组扫描使用417个STR标记在130个受影响兄弟姐妹对的家庭中显示，10条染色体（1、2、3、4、5、8、9、14、17和20）至少有一个区域，p值< 0.05。第二次全基因组扫描使用了236个日本家庭的5861个snp，其中包括第一次扫描中使用的122个snp，结果显示精神分裂症与1p21.1-1p13.1有关联的显著证据，以及与14q11.2、4q11.2-q13.2和20p12.1-p11.2有关联的暗示证据。基于精神分裂症发病机制的谷氨酸能功能障碍假说，我们对谷氨酸受体基因与精神分裂症的关系进行了系统的研究。我们选择了分布在相关基因区域的snp进行分型，并进行了单标记和单倍型关联研究。我们发现gr2d、GRIA4、GRM3和GRM8基因型与精神分裂症有显著关联。使用27,000个STR标记的全基因组关联研究正在进行中。第二组筛查显示720个标记与精神分裂症显著相关。第三组和第四组筛查和密集SNP分型将阐明精神分裂症的易感位点。研究人员对87例结核病患者和265例对照者的21个候选基因进行了118个标记单核苷酸多态性（snp）的基因关联分析。随后，我们分析了结核与邻近阳性标记snp的编码snp （csnp）之间的关系。三个1L的cSNPs。12RB1基因与结核的发展有显著相关性，提示1L_12RB1基因对日本人结核具有遗传易感性。我们还收集了56例分枝杆菌感染易感性患者的血液样本，并在3例无关的卡介苗骨髓炎患者及其父亲中鉴定出部分显性IFN-y受体1缺乏。这是日本首次报道这种疾病。

1. Study on schizophrenia susceptibilityThe first genome-wide scan using 417 STR markers in 130 families with affected sib-pairs revealed that ten chromosomes (1, 2, 3, 4, 5, 8, 9, 14, 17, and 20) had at least one region with a nominal p value < 0.05. The second genome-wide scan using 5,861 SNPs in 236 Japanese families including 122 ones used in the first scan revealed that significant evidence of linkage of schizophrenia to 1p21.1-1p13.1 and suggestive evidence of linkage to 14q11.2, 4q11.2-q13.2 and 20p12.1-p11.2.Based on the glutamatergic dysfunction hypothesis for the pathogenesis of schizophrenia, we conducted a systematic study of associations between glutamate receptor genes and schizophrenia. We selected SNPs evenly distributed across the relevant gene region for typing and did single marker and haplotype association studies. We found significant associations of halotypes of GRIN2D, GRIA4, GRM3 and GRM8 with schizophrenia. Genome- wide association study using 27,000 STR markers is on the way. The second set of screening showed significant associations of 720 markers with schizophrenia. The third and fourth sets of screening followed by dense SNP typing will elucidate the susceptibility loci for schizophrenia.2. Study on tuberculosis susceptibilityWe performed a gene-based association analysis of 21 candidate genes on 87 TB patients and 265 controls using 118 marker single nucleotide polymorphisms (SNPs). Subsequently, we analyzed the association between TB and coding SNPs (cSNPs) adjacent to positive marker SNPs. Three cSNPs of 1L.12RB1 were significantly associated with the development of TB, suggesting that 1L_12RB1 confers genetic susceptibility to TB in Japanese. We also collected blood samples from 56 patients who showed susceptibility to mycobacterial infection, and identified partial dominant IFN-y receptor 1 deficiency in 3 unrelated patients with BCG osteomyelitis and in one of their fathers. This is the first report of this disorder in Japanese.