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LOCAL ANCESTRY INFERENCE AND ITS IMPLICATION IN SEARCHING FOR SELECTION EVIDENCE IN RECENT ADMIXED POPULATION

Wang, Heming
http://orcid.org/0000-0002-1486-7495
http://rave.ohiolink.edu/etdc/view?acc_num=case1473439566976121

Abstract Details

2017, Doctor of Philosophy, Case Western Reserve University, Epidemiology and Biostatistics.
There has been increasing interest in studying the ancestral spectrum in admixed individuals, such as African Americans and Latino Americans. Investigating the different ancestral proportions across an individual’s genome, i.e. the local ancestries, is important in genetic studies. Many methods have been developed to infer the local ancestries in admixed individuals from their genotype data. A few of them have attempted to extend their methodologies to small nuclear families, but none can be applied to large pedigrees. We developed a method named FamANC that is able to improve the accuracy of local ancestry inference in large pedigrees by: 1) using existing software to infer local ancestries for all individuals in a family, assuming they are unrelated, 2) improving inference accuracy by correcting the inference errors. From our simulations, FamANC reduced the local ancestry estimation errors by over 20%. The second part of this dissertation is on searching for the epistasis of fitness evidence using local ancestries. The role played by epistasis between alleles at unlinked loci in shaping population fitness has been debated for many years. However, existing evidence has been mainly accumulated from model organisms. In model organisms, fitness epistasis can be systematically inferred by detecting non-independence of genotypic values between loci in a population and confirmed through examining the number of offspring produced in two-locus genotype groups. No systematic study has been conducted to detect epistasis of fitness in humans owing to experimental constraints. In this study, we theoretically demonstrate that fitness epistasis can create correlation of local ancestry between unlinked loci that can be examined. We inferred local ancestry across the genome in 16,252 unrelated African Americans and systematically examined the pairwise correlations between the genomic regions on different chromosomes. Our analysis revealed a pair of genomic regions on chromosomes 4 and 6 that show significant local ancestry correlation (p-value = 4.01 × 10-8) that can be potentially attributed to fitness epistasis. To our knowledge, this study is the first to systematically examine evidence of fitness epistasis across the human genome.
Xiaofeng Zhu (Committee Chair)
Robert Elston (Committee Member)
Nathan Morris (Committee Member)
Xiang Zhang (Committee Member)
123 p.
African Americans; Bioinformatics; Biostatistics; Epidemiology; Genetics; Statistics
local ancestry inference, admixed population, coevolution, epistasis of fitness, selection

Recommended Citations

Citations

  • Wang, H. (2017). LOCAL ANCESTRY INFERENCE AND ITS IMPLICATION IN SEARCHING FOR SELECTION EVIDENCE IN RECENT ADMIXED POPULATION [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1473439566976121

    APA Style (7th edition)

  • Wang, Heming. LOCAL ANCESTRY INFERENCE AND ITS IMPLICATION IN SEARCHING FOR SELECTION EVIDENCE IN RECENT ADMIXED POPULATION. 2017. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1473439566976121.

    MLA Style (8th edition)

  • Wang, Heming. "LOCAL ANCESTRY INFERENCE AND ITS IMPLICATION IN SEARCHING FOR SELECTION EVIDENCE IN RECENT ADMIXED POPULATION." Doctoral dissertation, Case Western Reserve University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1473439566976121

    Chicago Manual of Style (17th edition)

case1473439566976121
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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.