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Title: A genetic analysis of autosomal recessive forms of retinitis pigmentosa
Author: Bruford, Elspeth A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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The aim of this project was to identify loci for recessive forms of RP by genetic linkage analysis, using patients with arRP and BBS, and to test for mutations in any resultant candidate genes. Pedigrees with arRP from south-central Sardinia, an ethnic outlier with a higher prevalence of recessive disease, were studied initially. Linkage analysis was carried out using genome-wide microsatellite markers, and genetic heterogeneity was identified among the 11 families studied. Examination of the data revealed potential linkage to D14S80, on chromosome 14q11, in a subset of families. Fine mapping with further markers in this region identified a region of homozygosity in one consanguineous family, suggesting identity-by-descent. A strong candidate gene for RP, neural retina specific leucine zipper (NRL), was found to be located with the region of homozygosity. NRL codes for an evolutionarily conserved protein which is expressed in all layers of the neural retina, and is thought to have a role in the transcriptional regulation of retinal genes, including rhodopsin. The NRL gene was studied in the consanguineous family by direct sequencing and mutation analysis, but no mutations were identified within the coding region. A total of 28 BBS pedigrees collected worldwide were studied using markers in regions where linkage was established during the course of the study. These loci are located on chromosomes 11q13, 16q21, 3p13-p12 and 15q22.3-q23. The results revealed significant genetic heterogeneity, with most families showing linkage to 11q13, and others being consistent with linkage to the 16q or 15q chromosomal regions. Some of the larger pedigrees could be assigned to specific loci, but many of the smaller families were too small for a definite assignment. The results of multipoint linkage analyses in these three linked chromosomal regions will help narrow down the region of search for candidate genes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available