Demographic inference and genetic mapping in a founder population

Complex trait mapping is a difficult endeavor and multiple strategies have been proposed to facilitate mapping efforts, including studying founder populations (Lander and Schork 1994). In addition to the suggestion that genes for complex traits might be found more easily in founder populations relative to large outbred populations (see Lander and Schork 1994), the demographic and genetic processes that led to their formation may be used for testing population genetics hypotheses. Specifically, by using the genealogical, phenotypic, and genotypic data collected for complex trait mapping, one can also study the evolution, history, and micro-differentiation of these populations (for example, see Martin 1970). Furthermore, research goals in genetic mapping and populations genetics are not independent and studies of evolutionary processes in founder populations may inform efforts to map genes and vice versa .; In order to both inform mapping efforts in the Hutterite population and to explore population genetic hypotheses, I have studied the genealogical and genotypic data for one of the three subdivisions of the Hutterites, a young founder population of European origin. This study of Hutterite population history and genetics has implications for mapping studies in other populations, as well as general implications for human population history. First, I have quantified the effects of misspecifiying kinship in a linkage study of an inbred nuclear family and devised a pragmatic approach for such analyses when full inbreeding information cannot be used because of computational constraints. Second, I have demonstrated a loss of mt and Y-haplotype diversity in the Hutterite population over its 13 generation history. Third, I have uncovered a correlation in family size and suggest that this correlation: (1) is contributing to the loss of diversity in this population, (2) indicates genetic components to fertility are segregating in this population, and (3) represents a demographic parameter that should be included in models of human paleodemography. Fourth, two methods based on simulations are presented that are capable of identifying excess sharing at neutral sex-specific markers among founders (mt and Y haplotypes), relative to the sharing due to chance.*; *This dissertation is a compound document (contains both a paper copy and a CD as part of the dissertation). The CD requires the following system requirements: Adobe Acrobat.