The sampling distribution of disease-associated alleles.
The sampling distribution of disease-associated alleles.
复制标题
疾病相关等位基因的抽样分布。
DOI：
10.1093/genetics/147.4.1855
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发表时间：
1997
期刊：
影响因子：
3.3
通讯作者：
Rannala,B
中科院分区：
文献类型：
--
作者：
Slatkin,M;Rannala,B
在假设每个等位基因都是一个独特突变的结果的前提下，提出了在单个基因座上提供低频等位基因抽样分布的理论。假设每个等位基因的拷贝数遵循一个线性的出生-死亡过程。如果群体的规模一定，生灭过程理论的标准结果表明，每个等位基因的拷贝数的分布是对数的，在一定规模的样本中发现的等位基因拷贝数的联合分布遵循伊文斯抽样分布。如果获得样本的群体的规模在增加，如果等位基因的选择性类别不同，或者等位基因之间的外显率存在差异，则伊文斯分布不再适用。给定一组观测值的似然函数是在不同的备选假设下得到的。这些结果适用于已发表的人类brca1基因座（与早发性乳腺癌相关）和因子VIII基因座（与A型血友病相关）的数据。在这两种情况下，等位基因的抽样分布允许拒绝零假设，但相对较小的偏离零模型可以解释数据。特别是，大致相同的人口增长率似乎与两组数据一致。
A theory is developed that provides the sampling distribution of low frequency alleles at a single locus under the assumption that each allele is the result of a unique mutation. The numbers of copies of each allele is assumed to follow a linear birth-death process with sampling. If the population is of constant size, standard results from theory of birth-death processes show that the distribution of numbers of copies of each allele is logarithmic and that the joint distribution of numbers of copies ofkalleles found in a sample of sizenfollows the Ewens sampling distribution. If the population from which the sample was obtained was increasing in size, if there are different selective classes of alleles, or if there are differences in penetrance among alleles, the Ewens distribution no longer applies. Likelihood functions for a given set of observations are obtained under different alternative hypotheses. These results are applied to published data from theBRCA1locus (associated with early onset breast cancer) and the factor VIII locus (associated with hemophilia A) in humans. In both cases, the sampling distribution of alleles allows rejection of the null hypothesis, but relatively small deviations from the null model can account for the data. In particular, roughly the same population growth rate appears consistent with both data sets.