Theoretical Population Genetics

描述（由申请人提供）：该项目涉及开发新的人口遗传数据的统计方法。注意力将集中在三个主要领域与等位基因组之间的依赖关系：人口结构的表征，内和遗传标记和沿着单倍型之间的关联模式的表征，以及个人的相关性和近亲繁殖的表征。理论的发展至少部分是为了满足当前人类大规模SNP调查的需要，并期待全基因组序列数据集的出现。这项工作是由华盛顿大学生物统计学系的一组研究人员提出的。他们建议继续与W.G.合作。希尔和昆士兰州医学研究所的P. M.维舍尔。这个扩大的小组在上一个颁奖期间成功地进行了互动，40份出版物就是证明。S.R.的Beagle方法。和BL。布朗宁将被应用于通过血统来检测身份的区域。由此产生的关系的措施将被用来完善测试标志物与疾病的关联，并估计复杂的人类性状的遗传性。B.S. Weir和W.G. Hill将应用于最近发表的全基因组SNP数据集和全基因组序列数据集。将寻求方法来改进关于这些量的推论的方法。通过血统和人口结构来衡量同一性，有可能确定人类基因组中受到自然选择的区域，在进行这些分析时，将注意到进化过程造成的巨大变异和偏斜。C.C.的工作劳里和B. S.威尔关于通过检查单个SNP与来自大组SNP的主成分的相关性来检测染色体特征（如倒位）的研究将得到扩展。偏回归方法引入QTL定位将适用于这个问题。不依赖于基因型阶段的连锁不平衡的措施被引入，并已被这些研究人员以前使用。现在，他们将扩展到对基因座之间的不平衡的情况下，当几个SNPs类型为每个基因。关联映射仍然是相当大的兴趣，人类遗传学家和会计（即使是低水平）的相关性的问题将得到解决。例如，在病例对照研究中忽略至少有一个亲属的个体可能会导致权力的丧失。以前的工作Y。Choi和B.S. Weir认为，修改后的简单等位基因关联检验将扩展到更合适的逻辑回归方法。

DESCRIPTION (provided by applicant): This project is concerned with developing new statistical methodology for population genetic data. Attention will be focused on three main areas concerned with dependencies among sets of alleles: the characterization of population structure, the characterization of the association patterns within and between genetic markers and along haplotypes, and the characterization of relatedness and inbreeding for individuals. Theory will be developed at least in part in response to the needs of current large-scale SNP surveys for humans and in anticipation of whole-genome sequence data sets. The work is proposed by a group of investigators in the Department of Biostatistics at the University of Washington. They propose to continue collaboration with W.G. Hill at the University of Edinburgh and P.M. Visscher at the Queensland Institute of Medical Research. This extended group has interacted successfully over the previous award period, as evidenced by a set of 40 publications. The Beagle approach of S.R. and B.L. Browning will be applied to the detection of tracts of identity by descent. The resulting measures of relationship will be used to refine tests for marker-disease association and to estimate heritability of complex human traits. The population-specific measures of population structure described by B.S. Weir and W.G. Hill will be applied to recently published whole-genome SNP data sets and whole-genome sequence data sets. Methods will be sought to improve methods of drawing inferences about these quantities. Measures of identity by descent and of population structure have the potential to identify regions of the human genome that have been subject to natural selection, and these analyses will be conducted with attention to the large variation and skewness imposed by the evolutionary process. The work of C.C. Laurie and B.S. Weir on detecting chromosomal features, such as inversions, by examining correlations of individual SNPs with principal components derived from large sets of SNPs will be extended. The partial regression approach introduced for QTL mapping will be applied to this problem. Measures of linkage disequilibrium that do not depend on genotypic phase were introduced and have been used previously by these investigators. They will now be extended to the situation of disequilibrium between pairs of loci when several SNPs typed for each gene. Association mapping continues to be of considerable interest to human geneticists and the problem of accounting for (even low level) relatedness will be addressed. Ignoring individuals with at least one relative in a case-control study, for example, can lead to a loss of power. Previous work of Y. Choi and B.S. Weir that modified simple allelic association tests will be extended to the more appropriate logistic regression methods.