Date of Award
Fall 2023
Document Type
Open Access Dissertation
Department
Biological Sciences
First Advisor
Shannon Davis
Abstract
Peromyscus are the most prevalent mammalian species in North America, and they're employed extensively in both laboratory and field studies. P. maniculatus and P. polionotus, the deer mouse and the old-field mouse, are closely related and can produce viable and fertile hybrid offspring. However, a comprehensive database of polymorphisms, particularly in those kept as living stocks and supplied to university researchers, is lacking. In chapter 2, we performed comparative genomic study on P. maniculatus and P. polionotus and used the polymorphic data to identify the range of genetic complexity that underlies physiological and behavioral differences between two species. We also used the polymorphism data to do a candidate gene linkage analysis for the Dominant spot trait, which is characterized by a large white spot on the forehead. We linked Dominant spot to a region of chromosome 20 that has a strong candidate gene, Sox10, a key transcription factor for neural crest and melanocyte development. In the linkage analysis, we also discovered that the spot size in affected Peromyscus differed quantitatively depending on genetic background. These preliminary data support our fundamental hypothesis that Dominant spot is caused by a mutation in regulatory area of Sox10, and modifier genes interact with Sox10 gene expression to create variability in the dominant spot phenotype. In chapter 3, Next-generation sequencing (NGS) was conducted on Dominant spot mice to identify variants in the linked region. A large number of single nucleotide and small insertions or deletions (indels) variants from the reference genome were identified that are associated with the Dominant spot trait. A 615 bp insertion 100 kb downstream of the Sox10 gene in the linked interval was also found using a de novo assembly method. To identify loci containing potential modifier genes for Dominant spot, association analysis between SNPs and spot size phenotype in 50 mice at the extremes of the spot size distribution was performed. Restriction site-associated DNA sequencing (RAD-seq) was used to identify sequence variants and the variants associated with large and small spots. An approximately 1 Mb region on chromosome 10, containing three genes, was identified that correlates with spot size variability. These genes are candidate genes for modifiers of the spot size variability observed in Dominant Spot. Together, this study provides insights into the identification of variants that potentially regulate Sox10, which will lead to further understanding of the neural crest gene regulatory network.
Rights
© 2024, Zhenhua Shang
Recommended Citation
Shang, Z.(2023). Application Of Computational Tools To Identify Variations Associated With Peromyscus Dominant Spot. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/7526