Genomic structural characterization of the Greater Middle East to assist in the identification of disease variation
Year: 2015
Type: dissertation
Abstract: Our improved understanding of cellular biology, and, in a larger sense, human variability, relies on the accurate identification and analysis of disease-causing variants. Through the study of natural and artificial genetic damage, we’ve helped identify gene function, compile protein interaction networks and, reclassify human diseases by their underlying biology. Such discoveries have allowed the repurposing of treatments based on improved understanding of underlying mechanism and increased the adoption of genetic screening, both of which have made great headway in decreasing the human suffering caused by genetic disease.Despite working in the simplest constructs of genetic disease, with established expectations of inheritance and complete penetrance, the identification of causal mutations remains challenging. This is due in no small part due to incomplete assessment of human genetic diversity. The human genome has been found to have a high background burden of predicted damaging variation and a propensity for rare variation to remain population specific. Here we demonstrate multiple contributions to the field. We built a series of pipelines tasked with the through analysis of exome data for purpose of identification of disease variants, analyzed the genetic structure of the Greater Middle East to aid in future genetic-studies in these regions, and approach open genetics questions including the role of genetic purging in the background distribution of disease-causing variants.
Author: Eric Scott
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: St. Giles Foundation, Yale University, Dubai Harvard Foundation for Medical Research, Broad Institute, Georgia Clinical and Translational Science Alliance, King Abdulaziz City for Science and Technology, National Institutes of Health, Qatar National Research Fund, National Human Genome Research Institute, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Yale Center for Mendelian Disorders, Molecular Characterization of Joubert Syndrome, Large Scale Sequencing and Analysis of Genomes, G223034706, G4344307963, G4523020920, G5183736941, Inborn errors of immunity in children with herpes simplex encephalitis, Cellular and Molecular Defects in Human B Cell Development, G6506886395, Developmental Mechanisms of Human Structural Brain Defects, Molecular genetic dissection of epidermodysplasia verruciformis, G770899802, Genome-Wide Dissection of Mendelian Susceptibility to Mycobacterial Disease
OpenAlex ID: W2585803892