MAPPING GENES FOR NEPHROPATHY IN IDDM

糖尿病肾病（肾病）是一个主要的健康问题，在大多数 发达国家 多项研究表明， 糖尿病肾病的聚集性，与以下假设一致， 一个或多个主要基因效应也使个体易患IDDM NIDDM发展为肾病。该提案的目标是， 作为IRPG的一个组成部分提交，是可以将任何染色体区域 携带有肾病风险的基因。 寻找的策略 连锁将基于不一致的同胞对（DSP），兄弟姐妹 与胰岛素依赖型糖尿病一致，但与肾病不一致。 对于患有 高兄弟姐妹风险，DSP比同等产品强大得多 受影响的兄弟姐妹对的数量。 一旦有了积极的发现，我们 然后通过应用连锁不平衡来缩小有希望的区域 将方法映射到DSP系列和附加数据。 本提案的具体目标如下：1.设立两 一组DNA来自有一对胰岛素依赖型糖尿病兄弟姐妹的家庭， 糖尿病肾病的不一致性：波士顿的120个家庭和 芬兰的家庭2从单纯形中建立两组DNA 有先证者患有胰岛素依赖型糖尿病和糖尿病肾病以及两者兼有的家族 父母生活：波士顿的200个家庭和芬兰的200个家庭。 目的寻找糖尿病肾病的遗传分离位点， 对波士顿120个DSP家族进行了全基因组扫描， 通量基因分型方法和多点连锁分析4.到 通过检查相同的区域，确认和完善积极的调查结果， 芬兰的120个DSP家庭和非裔美国糖尿病家庭 在鲍曼-格雷医学院收集的。为了缩小批判性 通过所有240个多重基因组的连锁不平衡分析 和400个单工家庭，为下一步做准备， 克隆。 这个计划成功的可能性很大。 通过组合 我们与鲍曼-格雷学院的研究人员一起努力， 正在绘制非裔美国人NIDDM肾病基因图谱的医学人员 家庭，拟议的IRPG将有一个很大的机会映射大多数 染色体区域携带易感基因， 在IDDM或NIDDM以及白人中发生肾病 就像黑人一样。

Diabetic kidney disease (nephropathy) is a major health problem in most developed countries. Several studies have shown strong familial clustering of diabetic nephropathy, consistent with a hypothesis that one or more major gene effects predispose individuals with IDDM as well as NIDDM to develop nephropathy. The goal of this proposal, which is submitted as a component of an IRPG, is to may any chromosomal regions harboring genes that confer risk of nephropathy. The strategy to find linkage will be based on discordant sib pairs (DSPs), siblings concordant for IDDM but discordant for nephropathy. For a disease with a high sibling risk, DSPs are much more powerful than an equivalent number of affected sib pairs. Once positive findings are obtained, we will then narrow promising regions by applying linkage disequilibrium mapping methods to the DSP families and to additional data. The specific aims of this proposal are as follows: 1. To establish two panels of DNA from families with pairs of IDDM siblings that are discordant for diabetic nephropathy: 120 families in Boston and 120 families in Finland 2. To establish two panels of DNA from simplex families having probands with IDDM and diabetic nephropathy and both parents living: 200 families in Boston and 200 families in Finland 3. To search for genetic loci segregating with diabetic nephropathy with a total genome scan of the 120 DSP families in Boston with high throughput genotyping methods and multipoint linkage analysis 4. To confirm and refine positive findings by examining the same regions using the 120 DSP families in Finland and African-American diabetic families collected at the Bowman-Gray Medical School 5. To narrow critical region(s) through linkage disequilibrium analysis of all 240 multiplex and 400 simplex families in preparation for the next step, positional cloning. The proposed project has a high probability of success. By combining our effort with that of investigators from Bowman-Gray School of Medicine who are mapping genes for nephropathy in African-American NIDDM families, the proposed IRPG will have a very chance of mapping most chromosomal regions which harbor susceptibility genes for the development of nephropathy either in IDDM or NIDDM and in whites as well as in blacks.