Dissertation
The Identification and Characterization of a Genome-Wide Significant Region Associated with Erythrocyte Phenotypes in Domestic Sheep
Doctor of Philosophy (PhD), Washington State University
01/2015
Handle:
https://hdl.handle.net/2376/117609
Abstract
Genome-wide association studies (GWAS) have been used to identify associations between genetic variants and a given phenotype. A GWAS investigating seven red blood cell (RBC) phenotypes in over 500 domestic sheep (Ovis aries) from three breeds (Columbia, Polypay, and Rambouillet) identified a single nucleotide polymorphism (SNP) showing high association with increased mean corpuscular hemoglobin concentration and decreased mean corpuscular volume. The ovine HapMap project found the same genomic region has been under extreme historical selective pressure, demonstrating the importance of this region for survival, reproduction, and/or artificially selected traits.
Chapter 2 describes the initial investigation into the annotation and possible functional significance of this region. The implicated region is located near an expanded tandem repeat locus containing approximately 35 MYADM-like genes of varying length, and the overall expanded repeat locus has been observed only in the artiodactyl lineage. The MYADM protein contributes to proper membrane development, organization, and trafficking in myeloid cells. The specific RBC differences may be indicative of alterations in morphology. To our knowledge, nothing is known of the function of this MYADM-like expansion in the development of erythrocyte morphology. This chapter describes the development of a genetic marker to test the presence of an underlying functional mutation in the MYADM-like family of genes in sheep, and also identified new candidate genes impacting RBC morphology in other mammalian systems.
Chapter 3 involves the investigation of the intracellular cation content of sheep RBCs. Sheep erythrocytes fall into two distinct types, high (HK) and low (LK) intracellular potassium. This phenotypic dimorphism became a much used physiological model for ion transport in mammalian cells and has been studied for over 60 years; however, the genetic locus responsible was never fully elucidated. To this end, a GWAS investigating intracellular cation concentration in sheep erythrocytes was performed that identified the MYADMF expansion previously implicated in altered erythrocyte phenotypes and production values in multiple breeds of domestic sheep. Our continued efforts include further annotation and characterization of this genomic locus in sheep, as well as comparative genomic analysis in economically important artiodactyl species.
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Details
- Title
- The Identification and Characterization of a Genome-Wide Significant Region Associated with Erythrocyte Phenotypes in Domestic Sheep
- Creators
- Michael Vincent Gonzalez
- Contributors
- Stephen N. White (Advisor)Holly L. Neibergs (Committee Member)Kelly A. Brayton (Committee Member)Donald P. Knowles (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 250
- Identifiers
- 99900581837101842
- Language
- English
- Resource Type
- Dissertation