Date of Award
Doctor of Philosophy (PhD)
Dr. Leigh Anne Clark, Committee Chair
Dr. Susan C. Chapman
Dr. F. Alex Feltus
Dr. Keith E. Murphy
Dr. Michael G. Sehorn
If no reference genome exists, then the generation of a de novo genome assembly of an organism is necessary because having a reference genome expedites the discoveries for simple and complex traits. Reference genomes for the domestic dog (Canis lupus familiaris) and chicken (Gallus gallus) have resulted in the development of single nucleotide polymorphism (SNP) arrays for use in genome-wide association studies (GWAS). Next-generation sequencing technologies provide a rapid, increasingly affordable method for the generation of genome resequencing data. The first objective of this work was to utilize existing genomic resources to investigate the genetic basis for traits of the dog and chicken. Episodic falling syndrome (EFS) is a recessive neurological disease of Cavalier King Charles spaniels. Using SNP profiles from only 12 individuals, EFS was mapped to chromosome 7; further experimentation led to the identification of the causative deletion. In a second example, SNP profiles from 197 German shepherd dogs were generated to identify loci underlying numerous diseases afflicting the breed, including recessive pituitary dwarfism, and three complex diseases: degenerative myelopathy, megaesophagus, and pancreatic acinar atrophy. Lastly, SNP profiles for 60 Araucana chickens were used to identify an association with the semi-dominant tailless rump (rumpless) phenotype on chromosome 2, as well as the recessive lethal ear-tufts phenotype on chromosome 15. Positional candidate genes were identified for both traits. The second objective of this work was to identify loci associated with dermatomyositis (DM) and to develop resources to facilitate the identification of the causative mutation. DM is an inflammatory myopathy affecting humans and domestic dogs, primarily the collie and Shetland sheepdog breeds where painful lesions on the face and extremities are characteristics. The second objective was accomplished through 1) assembly of a population of DM-affected and healthy control collies, 2) completion of a GWAS using SNP profiles generated for this population, and 3) establishment of whole-genome resequencing data from 3 DM-affected collies and 2 healthy controls. Results revealed a strong association on chromosome 10. Annotation of the collie genome yielded novel SNPs, structural variants, and selective sweeps, and regions of reduced heterogeneity surrounding a gene(s) under strong positive selection.
Noorai, Rooksana Elizabeth, "Discovery of Variants Underlying Simple and Complex Traits through Genome-Wide Association Study and Whole-Genome Resequencing" (2014). All Dissertations. 1713.