Genetic mapping studies in the AS/AGU rat

Genetics

Canham, Maurice

University:University of Glasgow

关键词: Genetics;   

Others  :  http://theses.gla.ac.uk/71729/1/10391369.pdf

来源: University of Glasgow

【 摘 要 】

The AS/AGU rat arose by spontaneous mutation from a closed colony of AS rats in the Laboratory of Human Anatomy, The University of Glasgow, in 1990. These rats had locomotor abnormalities and appeared to have a striatal dopamine deficiency syndrome, symptoms and pathology reminiscent of human Parkinson's disease. Test crosses between AS/AGU and AS rats indicated that the mutant locus, agu, was inherited in an autosomal recessive fashion with no evidence of maternal or X-linked involvement. Two reference strains, BN and F344, were used to set up backcrosses with AS/AGU, namely, [AS/AGUxF1(AS/AGUxBN)] and [AS/AGUxF1(AS/AGUxF344)]. Previously, 75 microsatellites markers spanning the rat genome were tested for informativeness between AS/AGU and the strains BN and F344. In this study, 19 other microsatellites were typed on these strains, 9 of which displayed size differences and could therefore be mapped relative to agu. Two candidate chromosomes had been thought to harbour agu, one of which was eliminated in this report. Initially, four markers from the other chromosome had aU shown linkage with agu but none were close enough to commence chromosome walking to the disease locus. This report describes the analysis of pre-existing microsatellites and the search for new ones associated with a gene family believed to be adjacent to agu. A total of twelve markers, associated with this gene family, were analysed for size or sequence variation between AS/AGU and reference strains. None proved informative. It was concluded that members of this gene family had not diverged sufficiently between these strains. Another reference strain, DA, has been shown to display size differences from the AS strain from members of this gene family and other markers believed to be near agu. A backcross program using this reference strain is now underway. To date, another gene-based marker has been shown to be less than 0.5 cM from agu and physical mapping is now underway to track down a gene harbouring this mutation. The eventual discovery of such a gene and its role in normal physiology will prove valuable in the understanding of basal ganglia disorders.