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" Identifying and Analyzing Human Genetic Variation Through a Key Example in the Growth Hormone Receptor Gene "
Resendez, Skyler D.
Gokcumen, Omer
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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1113707
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| Doc. No
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TLpq2384556625
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| Main Entry
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Gokcumen, Omer
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Resendez, Skyler D.
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| Title & Author
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Identifying and Analyzing Human Genetic Variation Through a Key Example in the Growth Hormone Receptor Gene\ Resendez, Skyler D.Gokcumen, Omer
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| College
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State University of New York at Buffalo
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| Date
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2020
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| student score
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2020
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| Degree
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Ph.D.
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| Page No
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117
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| Abstract
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To define what it means to be human, we must first appreciate the full scope of human variation. This means we must consider both single nucleotide variants and structural variants to map human variation. The majority of human research tends to focus on the previous, despite the fact that structural variants conservatively constitute two to seven times more base pairs that are variable among primate species when compared to single-nucleotide variants. There are several methods of identifying structural variations in genomes. For short-reads sequences, these include read depth, split-read, and paired-end methodologies. Utilizing massive genomic databases that are available today, one can then discover important demographic information about a variant of interest and look to the genetic data collected in different populations and in ancient samples to begin to understand the evolutionary history of that variant. The methodologies outlined in this dissertation were followed to perform an evolutionary and phenotypic analysis of a common exonic deletion in the growth hormone receptor gene (GHRd3) that has only been observed in humans and extinct hominins. This deletion has been linked to response to growth hormone, placenta size, birth weight, growth after birth, time of menarche, adult height, and longevity. To further evaluate its phenotypic effects, a mouse line engineered to contain the deletion was used. Pleiotropic and sex-specific effects on organismal growth, the expression levels of hundreds of genes, and serum lipid composition were documented, potentially involving the nutrient-dependent mTORC1 pathway. Together with statistical analyses performed on this locus, these growth and metabolic effects are consistent with a model in which the allele frequency of GHRd3 varies throughout human evolution as a response to
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| Subject
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Biology
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Growth hormone receptor gene
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