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Mapping of vitiligo genes in the Smyth line chicken model for autoimmune human vitiligo
The Smyth line chicken (SL), a model for autoimmune human vitiligo is characterized by spontaneous, posthatch, destruction of melanocytes. Morphological and immunological changes accompanying the SL vitiligo has been well characterized, but information on the mode of inheritance of the disease is limited. In this study, a comprehensive genetic analysis was conducted to get a better picture of the genetics of this animal model. The DNA fingerprint analysis has revealed moderate level of inbreeding within the SL and BL parental sublines. 5-AzaC treatment increased the incidence of vitiligo in BL controls, while no changes were noticed in the unrelated LBL controls, providing the evidence that the BL sublines are genetically susceptible controls. High Embryonic mortality and low incidence of vitiligo were observed when the SL was used as the female parent in SL/BL matings. The number of affected females were higher, when SL was used as the male parent, suggestive of sex-linked inheritance. However, a model involving polygenic inheritance and genomic imprinting, better explain these data. Based on the results of the above experiments, SL101 and BL101 were selected to produce an F$\sb2$ population for the mapping of vitiligo genes. Genome scan was conducted with 156 microsatellite (MS) markers and 75 polymorphic markers were selected for the gene mapping. The results of the linkage analysis showed that MS markers on chromosome 1, 2 and linkage group 36 are linked to vitiligo. Candidate gene analysis revealed linkage disequilibrium between vitiligo and endogenous virus (EV) genes. EV genes were found to be expressed in SL chicken and 5-Azacytidine treated vitiliginous BL chickens. In situ hybridization experiments revealed one EV locus in LBL chickens (1q14) and 3 in SL101 and BL101 birds (1p25, 2q26 and a microchromosome). The results from this study suggests the possible effect of EV genes on SL vitiligo. One of the loci mapped on chromosome 2 is most likely an EV gene or one that is linked to it. The genes mapped at the other two loci are not identified at this time and a detailed positional cloning strategy would be necessary to identify the genes from these regions.
Pillai, Sreekumar Govinda, "Mapping of vitiligo genes in the Smyth line chicken model for autoimmune human vitiligo" (1998). Doctoral Dissertations Available from Proquest. AAI9823765.