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- All Subjects: Variant Calling
- Creators: Wilson Sayres, Melissa
Description
Hepatocellular carcinoma (HCC) is a type of liver cancer common in Sub-Saharan Africa and South East Asian countries. Each year more than 700,000 new cases and more than 600,000 deaths are recorded worldwide due to HCC. According to the American Cancer Society HCC is ranked the 5th most common cancer worldwide with a male:female susceptibility ratio ranging between 2:1 and 8:1. HCC risk factors include lifestyle behaviors, such as persistent alcohol abuse and smoking, prolonged exposure to aflatoxins, chronic viral hepatitis infections, inherited metabolic diseases and non-alcoholic fatty liver diseases. To understand the genetic effects underlying sex-bias in HCC, it is necessary to include the sex chromosomes in genomics analyses. X and Y chromosomes are often discluded in genomics studies because of the technical and analytical challenges: sequence homology. The purpose of this thesis is to analyze the effects of sex chromosome complement aware read mapping to germline variant calling. 10 male and 10 female tumor adjacent samples from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA LIHC) cohort were processed using sex-aware and default reference and the concordance of the two approaches was examined. We detected a higher disconcordance of 0.69% on variants called on the X chromosome and a disconcordance of 0.51% on variants called on the Y chromosomes for the reference and alternative alleles respectively compared to autosomes. Variants called on the REF/ALT genotypes had a disconcordances of 1.00%, 1.05%, 1.35% and 12.34% for the autosomes, chromosome 7, the X, and the Y chromosome, respectively. At the end of the project we concluded that the generated datasets showed the effect of sex-aware read mapping on variant calling. Though the data did not show the sites that can be called as variants in one dataset but not in the other, rather the concordance looked at sites that were called as variants in both data sets.
ContributorsPhiri, Lovender Teresa (Co-author) / Phiri, Lovender (Co-author) / Wilson Sayres, Melissa (Thesis director) / Buetow, Kenneth (Committee member) / Natri, Heini (Committee member) / School of Life Sciences (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Unlike the autosomes, recombination on the sex chromosomes is limited to the pseudoautosomal regions (PARs) at each end of the chromosome. PAR1 spans approximately 2.7 Mb from the tip of the proximal arm of each sex chromosome, and a pseudoautosomal boundary between the PAR1 and non-PAR region is thought to have evolved from a Y-specific inversion that suppressed recombination across the boundary. In addition to the two PARs, there is also a human-specific X-transposed region (XTR) that was duplicated from the X to the Y chromosome. Genetic diversity is expected to be higher in recombining than nonrecombining regions, particularly because recombination reduces the effects of linked selection, allowing neutral variation to accumulate. We previously showed that diversity decreases linearly across the previously defined pseudoautosomal boundary (rather than drop suddenly at the boundary), suggesting that the pseudoautosomal boundary may not be as strict as previously thought. In this study, we analyzed data from 1271 genetic females to explore the extent to which the pseudoautosomal boundary varies among human populations (broadly, African, European, South Asian, East Asian, and the Americas). We found that, in all populations, genetic diversity was significantly higher in the PAR1 and XTR than in the non-PAR regions, and that diversity decreased linearly from the PAR1 to finally reach a non-PAR value well past the pseudoautosomal boundary in all populations. However, we also found that the location at which diversity changes from reflecting the higher PAR1 diversity to the lower nonPAR diversity varied by as much as 500 kb among populations. The lack of genetic evidence for a strict pseudoautosomal boundary and the variability in patterns of diversity across the pseudoautosomal boundary are consistent with two potential explanations: (1) the boundary itself may vary across populations, or (2) that population-specific demographic histories have shaped diversity across the pseudoautosomal boundary.
ContributorsCotter, Daniel Juetten (Author) / Wilson Sayres, Melissa (Thesis director) / Stone, Anne (Committee member) / Webster, Timothy (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12