Retinitis pigmentosa (RP) is one of the major forms of blindness worldwide. It is inherited as autosomal dominant, recessive and X-linked disease. It is an important cause of childhood blindness in India, with the autosomal recessive mode of inheritance being the most prevalent in sections of the population, particularly in South India. RP is extremely heterogeneous and the identification of genes causing the disease is an essential step towards the design of therapeutic agents. Recessive RP in India is frequently associated with consanguinity. The goal of this study is to identify the genetic bases for recessive RP in India. This knowledge is expected to contribute towards an understanding of the pathophysiology of RP, and to be of potential use in the genetic counseling of patients. The approach that we plan to employ consists of: a) Screening families with recessive RP for homozygosity by descent at candidate gene loci. Microsatellite markers that flank several genes known to cause dominant and recessive RP as well as other types of retinal dystrophy will be screened for homozygosity in affected offspring versus parents. The presence of homozygosity at a given locus in affected individuals will be interpreted to mean that the locus is possibly segregating with disease and the relevant candidate gene will be screened for mutations, b) Identification of new loci by genome-wide linkage analysis. Families that are negative in the first screening step will be analyzed by genome-wide linkage analysis to identify disease loci. The use of large consanguineous pedigrees will facilitate this approach. Identified loci will be screened for potential candidate genes within that interval. Possible candidate genes will be analyzed for: 1) Expression in the retina/RPE 2) Sequence changes associated with disease.
| Singh, Hardeep Pal; Jalali, Subhadra; Narayanan, Raja et al. (2009) Genetic analysis of Indian families with autosomal recessive retinitis pigmentosa by homozygosity screening. Invest Ophthalmol Vis Sci 50:4065-71 |
| Singh, Hardeep Pal; Jalali, Subhadra; Hejtmancik, J Fielding et al. (2006) Homozygous null mutations in the ABCA4 gene in two families with autosomal recessive retinal dystrophy. Am J Ophthalmol 141:906-13 |
