Genome descent in isolated populations
Chapman, Nicola H., 1971-
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An isolated population is one that is descended from a small group of individuals (founders), and in which population growth is due almost exclusively to births within the population, rather than immigration from outside. Interest in the genetics of isolated populations has recently been revived among medical geneticists, because it is hoped that diseases for which there are several susceptibility loci in large outbred populations may be more homogeneous in small isolated populations. In addition, it has been suggested that small recently founded populations may exhibit linkage disequilibrium over longer genetic distances than large outbred populations.In this dissertation, I study the inheritance of segments of ancestral chromosomes. This is achieved by the study of junctions---points on the chromosome where segments from different ancestral chromosomes meet. I consider a discrete generation random mating population, and assume that population sizes over time are known. Two fundamental questions are addressed. First, how large are pieces of intact ancestral chromosome in chromosomes sampled from the population? The answer to this question provides information about the extent of linkage disequilibrium in the population. Second, how long are the tracts of chromosome which are shared identical-by-descent between randomly sampled chromosomes from the population? I also study how the age of the population, founding population size, growth patterns, and population subdivision affect both segment length, and the length of IBD tracts between randomly sampled chromosomes. I show that these factors have substantial effects in very small populations, but are less important in larger populations.The theoretical work about junctions in random mating populations is extended to the case where a pedigree is available. I introduce an approach to the estimation of fine-scale genetic maps, using data consisting of chromosomes sampled from an isolated population, and knowledge of the pedigree relating those chromosomes. The approach is demonstrated using a pedigree relating 27,163 Hutterites. I show that this approach has potential to produce more precise maps than currently exist, and that the Hutterite population is ideal for this application.
- Biostatistics