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Genome-Scale Insights Into the Underlying Genetics of Background Effects /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Genome-Scale Insights Into the Underlying Genetics of Background Effects /Joseph Hale.
Author:	Hale, Joseph,
Description:	1 electronic resource (202 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-09, Section: B.
Notes:	Advisors: Ehrenreich, Ian Committee members: Aparicio, Oscar; Dean, Matthew; Mooney, Jazlyn.
Contained By:	Dissertations Abstracts International85-09B.
Subject:	Molecular biology.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31139564
ISBN:	9798381967333

Genome-Scale Insights Into the Underlying Genetics of Background Effects /
Hale, Joseph,

Genome-Scale Insights Into the Underlying Genetics of Background Effects /Joseph Hale. - 1 electronic resource (202 pages)

Source: Dissertations Abstracts International, Volume: 85-09, Section: B.

A major goal of modern genetics is to fully understand how genetic variation influences phenotypic variation. A great deal of our knowledge on the genetic basis of phenotype comes from large-scale studies of many individuals. However, this does not always tell the entire story. The effects of genetic variants can be highly contextual, with some individuals exhibiting dramatically different responses to the same genetic variant. This phenomenon, known as a genetic background effect, means that simply understanding the average effect of a variant across an entire population may not translate to predictive power for individuals. Recent advances in DNA barcoding, sequencing, and CRISPR interference have made it possible to study these effects on an unprecedented scale, potentially enabling general, genome-scale insights into how genetic background effects play a role in determining phenotype. The aim of this dissertation is to utilize these new methods to provide a broad view into the background effects that occur in Saccharomyces cerevisiae. In this model system, I investigate how background effects alter the impact of spontaneous mutations, standing genetic variants segregating in a cross, and new genetic perturbations introduced through CRISPR interference. In chapter two, I investigate a specific mutation with a very high degree of variable expressivity, revealing that over 15 separate loci collectively influence the mutation's phenotypic impact. In chapter three, I use a similar panel of diploid yeast strains to investigate the relationship between additivity, dominance, and epistasis in the context of standing genetic variation, mapping the loci that underlie these effects across seven environments. In chapter four, I measure the effects of perturbing ~1,700 yeast genes across a panel of ~170 haploid yeast genotypes, identifying over 450 genetic perturbations with background-specific effects and mapping their underlying loci. These studies provide several genome-scale observations into the mechanisms of background effects as a whole and their underlying genetic bases.

English

ISBN: 9798381967333Subjects--Topical Terms:

188737
Molecular biology.
Subjects--Index Terms:

Background effects

Genome-Scale Insights Into the Underlying Genetics of Background Effects /
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520 $a A major goal of modern genetics is to fully understand how genetic variation influences phenotypic variation. A great deal of our knowledge on the genetic basis of phenotype comes from large-scale studies of many individuals. However, this does not always tell the entire story. The effects of genetic variants can be highly contextual, with some individuals exhibiting dramatically different responses to the same genetic variant. This phenomenon, known as a genetic background effect, means that simply understanding the average effect of a variant across an entire population may not translate to predictive power for individuals. Recent advances in DNA barcoding, sequencing, and CRISPR interference have made it possible to study these effects on an unprecedented scale, potentially enabling general, genome-scale insights into how genetic background effects play a role in determining phenotype. The aim of this dissertation is to utilize these new methods to provide a broad view into the background effects that occur in Saccharomyces cerevisiae. In this model system, I investigate how background effects alter the impact of spontaneous mutations, standing genetic variants segregating in a cross, and new genetic perturbations introduced through CRISPR interference. In chapter two, I investigate a specific mutation with a very high degree of variable expressivity, revealing that over 15 separate loci collectively influence the mutation's phenotypic impact. In chapter three, I use a similar panel of diploid yeast strains to investigate the relationship between additivity, dominance, and epistasis in the context of standing genetic variation, mapping the loci that underlie these effects across seven environments. In chapter four, I measure the effects of perturbing ~1,700 yeast genes across a panel of ~170 haploid yeast genotypes, identifying over 450 genetic perturbations with background-specific effects and mapping their underlying loci. These studies provide several genome-scale observations into the mechanisms of background effects as a whole and their underlying genetic bases.
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