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中国汉族人群Ⅱ型糖尿病家系1号染色体易感基因的精细定位
作者姓名:Du WN  Sun HX  Wang H  Qiang BQ  Yao ZJ  Gu J  Xiong MM  Huang W  Chen Z  Zuo J  Hua XF  Gao W  Sun Q  Fang FD
作者单位:1. 中国医学科学院中国协和医科大学基础医学研究所医学分子生物学国家重点实验室,北京,100005
2. Department of Endocrinology, PUMC Hospital, Beijing
3. Chinese National Human Genome Center at Beijing
4. Chinese National Human Genome Center at Shanghai
5. Department of Endocrinology, Yuhuangding Hospital of YanTai
基金项目:国家自然科学基金重大项目(39896200),国家高技术研究发展计划863重点项目基金(2001AA221161),国家重点基础性研究973项目基金(G1998051016),北京自然科学基金(7002026)资助
摘    要:目的 通过增加微卫星位点密度、扩大样本量、对以前定位到1号染色体上的中国北方汉族人群2型糖尿病相关易感基因研究结果进行验证。方法 运用基因组扫描的方法,经多重PCR、电泳、GeneScan及Genotyper程序分析获取位点信息,最后经参数及非参数连锁分析,得到相关的P值、NPL值(Z值)。结果 共扫描了5个区域34个位点,检出约12000个基因型。经GENEHUNTER 2.0软件分析,其中的8个位点可能与糖尿病相连锁(P<0.05,NPL值最大为2.17),它们分布于3个区域,尤其是第1个区域(1 p36.3-1p36.23),其每一个位点都显示与糖尿病相连锁,前后分布于1个长达16.9cM的范围内。另外2个区域未检出阳性结果。结论 证实了全基因组扫描所获得的结果。尤其是,在所研究的1P末端区域,所有研究位点都显示与疾病连锁,这些位点分布在一个很宽的范围内,提示该区域可能蛰伏着多个糖尿病易感基因。

关 键 词:中国  汉族人群  2型糖尿病  微卫星位点  基因组扫描  易感基因  基因定位
修稿时间:2001年12月3日

Fine mapping of susceptibility genes loci within chromosome 1 in Chinese Han families with type 2 diabetes
Du WN,Sun HX,Wang H,Qiang BQ,Yao ZJ,Gu J,Xiong MM,Huang W,Chen Z,Zuo J,Hua XF,Gao W,Sun Q,Fang FD.Fine mapping of susceptibility genes loci within chromosome 1 in Chinese Han families with type 2 diabetes[J].Acta Academiae Medicinae Sinicae,2002,24(3):234-237.
Authors:Du Wei-nan  Sun Hong-xia  Wang Heng  Qiang Bo-qin  Yao Zhi-jian  Gu Jun  Xiong Mo-miao  Huang Wei  Chen Zhu  Zuo Jin  Hua Xiu-feng  Gao Wei  Sun Qi  Fang Fu-de
Institution:National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS and PUMC, Beijing 100005, China.
Abstract:Objectives To confirm previous whole-genome scan results of mapping type2diabetes susceptibility genes in chromosome 1in Northern Chinese Han population by conducting a new genome scan with both an enlarged number of type2diabetes families and a new set of microsatellite markers.Methods A genome scan method was applied.After multiplexed PCR,electrophoreses,genescan and genotyping analysis,size informations for all loci were obtained,and a further study was done using both parametric and non-parametric linkage analysis to calculate the P-values and Z-values of these loci.Results A total of34microsatellite markers distributed within5regions along chromosome 1were surveyed,and12000genotypes were screened.Evidence of linkage with diabetes was identified for8of the34loci(all the P-values of the8loci distributed in3regions were lower than0.05,and the highest Z-value was2.17).Interestingly,all the5markers at the P terminal1p36.3-1p36.23region,spanning a long range of16.9cM,suggested to be linked with the disease.The results of the other two regions were not consistent with the previous ones.Conclusions The study results have confirmed those gained in the previous genome -wide scan.The fact that all5loci at the P terminal region displayed linkage with diabetes suggests that more than1susceptibility gene may reside in this region.
Keywords:type2diabetes  microsatelliter markers  genome  scan  susceptible genes  gene mapping
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