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Investigating the Role of Genomic Variation in Susceptibility to Environmental Chemicals across Populations
Başlık:
Investigating the Role of Genomic Variation in Susceptibility to Environmental Chemicals across Populations
Yazar:
Holden, Lindsay Adrian, author.
ISBN:
9780438133266
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (146 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Includes supplementary digital materials.
Advisors: Kim H. Brown Committee members: Bradley Buckley; Suzanne Estes; Deborah Lutterschmidt; Angela Strecker.
Özet:
No two individuals are identical. This is true at the genetic level and at the phenotypic level. One of the traits that varies between populations is toxicant susceptibility: some individuals are sensitive to the effects of environmental chemical exposure, and others are resistant. This body of work aims to address the impact of genomic copy number variants (CNV)---large (>1 Kb) duplications or deletions across the genome---on the toxicant-susceptibility phenotype.
Herein I have characterized copy number variants across three commonly used laboratory strains of zebrafish (Danio rerio) and identified mRNA expression phenotypes in the same strains. I found that males and females have only a 14% overlap in differentially expressed mRNA transcripts across three common laboratory strains, congruent with the growing body of work identifying sex- and strain-specific phenotypes in zebrafish. Furthermore, I identified two strain-specific response quantitative trait loci (QTL) that explain about a third of the variation in susceptibility to PCB and tested the response QTL using targeted CRISPR-Cas9 editing of the CNV involved. Overall, this body of work defines CNV and mRNA expression variation across zebrafish strains, identifies CNV causal in the PCB-susceptibility phenotype, and confirms the PCB-susceptibility QTL using targeted genomic editing.
Notlar:
School code: 0180
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(691999.1) | 691999-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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