Monogenic Traits Associated with Structural Variants in Chicken and Horse
Year: 2015
Type: dissertation
Abstract: Domestic animals have rich phenotypic diversity that can be explored to advance our \nunderstanding of the relationship between molecular genetics and phenotypic variation. Since \nthe advent of second generation sequencing, it has become easier to identify structural variants \nand associate them with phenotypic outcomes. This thesis details studies on three such variants \nassociated with monogenic traits. \nThe first studies on Rose-comb in the chicken were published over a century ago, seminally \ndescribing Mendelian inheritance and epistatic interaction in animals. Homozygosity for the \notherwise dominant Rose-comb allele was later associated with reduced rooster fertility. We \nshow that a 7.38 Mb inversion is causal for Rose-comb, and that two alleles exist for Rose-comb, \nR1 and R2. A novel genomic context for the gene MNR2 is causative for the comb phenotype, \nand the bisection of the gene CCDC108 is associated with fertility issues. The recombined R2 \nallele has intact CCDC108, and normal fertility. \nThe dominant phenotype Greying with Age in horses was previously associated with an \nintronic duplication in STX17. By utilising second generation sequencing we have examined the \ngenomic region surrounding the duplication in detail, and excluded all other discovered variants \nas causative for Grey. \nDun is the ancestral coat colour of equids, where the individual is mostly pale in colour, but \ncarries intensely pigmented primitive markings, most notably a dorsal stripe. Dun is a dominant \ntrait, and yet most domestic horses are non-dun in colour and intensely pigmented. We show that \nDun colour is established by radially asymmetric expression of the transcription factor TBX3 in \nhair follicles. This results in a microscopic spotting phenotype on the level of the individual hair, \ngiving the impression of pigment dilution. Non-dun colour is caused by two different alleles, \nnon-dun1 and non-dun2, both of which disrupt the TBX3-mediated regulation of pigmentation. \nNon-dun1 is associated with a SNP variant 5 kb downstream of TBX3, and non-dun2 with a 1.6 \nkb deletion that overlaps the non-dun1 SNP. Homozygotes for non-dun2 show a more intensely \npigmented appearance than horses with one or two non-dun1 alleles. We have also shown by \ngenotyping of ancient DNA that non-dun1 predates domestication.
Author: Freyja Imsland
Language: English
Subfield: Genetics
Domain: Life Sciences
SDG: Zero hunger
Open Access status: green
OpenAlex ID: W1804269831