Detection of genetic heterogeneity among pedigrees through complex segregation analysis: an application to hypercholesterolemia.
Detection of genetic heterogeneity among pedigrees through complex segregation analysis: an application to hypercholesterolemia.
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通过复杂分离分析检测家系间的遗传异质性：在高胆固醇血症中的应用。
DOI：
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发表时间：
1984
影响因子：
9.8
通讯作者：
B. Kottke
中科院分区：
文献类型：
--
作者：
P. Moll;T. Berry;W. Weidman;R. Ellefson;H. Gordon;B. Kottke
研究数量性状极端水平的遗传异质性的几种方法需要对家系进行先验分层和/或在受影响的个体中识别不同的表型。我们提出了一种检测遗传异质性的统计方法，它既不依赖于先验分层，也不依赖于离散的疾病表型。对明尼苏达州罗切斯特市3666名学龄儿童中选择的98名健康指数病例的709名亲属的血清总胆固醇水平进行了复合分离分析。其中33例患者和109名亲属患有高胆固醇血症(他们的年龄和性别的胆固醇水平高于第95个百分位数)。通过应用混合遗传模型和主基因座存在突变等位基因的条件概率估计，揭示了高胆固醇血症的遗传异质性。在70个有一个或多个高胆固醇症的家系中，有三个有强有力的证据表明一个主要基因座存在分离。在剩下的家系中，只有多基因变异和/或环境变异与胆固醇变异性相关。在主要基因座分离的三个家系中，祖父母死于冠心病的比率最高。这项研究表明，混合模型有可能识别数量性状变异具有不同遗传病因的家系。
Several methods for investigating genetic heterogeneity for extreme levels of a quantitative trait with hypothesized multiple genetic etiologies require a priori stratification of families and/or identification of distinct phenotypes among affected individuals. We present a statistical approach for detecting genetic heterogeneity that does not rely on either a priori stratification or discrete disease phenotypes. Complex segregation analysis was applied to total serum cholesterol measurements in 709 relatives of 98 healthy index cases selected from 3,666 school children surveyed for lipid levels in Rochester, Minnesota. Thirty-three of the index cases and 109 relatives had hypercholesterolemia (cholesterol levels greater than the 95th percentile for their age and sex). Through application of the mixed genetic model and then estimation of conditional probabilities for having the mutant allele at the major locus, genetic heterogeneity for hypercholesterolemia was indicated. In three of 70 pedigrees with one or more hypercholesterolemics, there is strong evidence for segregation at a major locus. In the remaining pedigrees, only polygene variation and/or environmental variation are associated with cholesterol variability. Grandparents in the three pedigrees that were segregating at the major locus had the highest rates of death due to coronary heart disease. This study establishes that the mixed model has the potential to identify pedigrees with different genetic etiologies for variability in quantitative traits.
DOI：
10.1016/0010-4809(82)90064-7
发表时间：
1982-01-01
期刊：
COMPUTERS AND BIOMEDICAL RESEARCH
影响因子：
--
作者：
HASSTEDT, SJ
通讯作者：
HASSTEDT, SJ
影响因子：
--
作者：
Cloninger,CR;Bohman,M;Sigvardsson,S
通讯作者：
Sigvardsson,S
低密度脂蛋白受体的纯化，一种分子量为 164,000 的酸性糖蛋白。
DOI：
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发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Schneider,WJ;Beisiegel,U;Goldstein,JL;Brown,MS
通讯作者：
Brown,MS