HOMOZYGOSITY MAPPING OF ACHROMATOPSIA TO CHROMOSOME-2 USING DNA POOLING

Achromatopsia is an autosomal recessive disease of the retina, charact erized clinically by an inability to distinguish colors, impaired visu al acuity, nystagmus and photophobia, A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran, To facilitate the genome-wide search, we utilized a DNA pooling strategy which take s advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder, Equal molar amounts of DNA from all affected individuals were pooled and use d as the PCR template for short tandem repeat polymorphic markers (STR Ps), Pooled DNA from unaffected members of the kindred was used as a c ontrol, A reduction in the number of alleles in the affected versus co ntrol pool was observed at several loci, Upon genotyping of individual family members, significant linkage was established between the disea se phenotype and markers localized on chromosome 2, The highest LOD sc ore observed was 5.4 (theta = 0), When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2, Analysi s of recombinant chromosomes revealed that the disease gene lies withi n a 30 cM interval which spans the centromere, Additional fine-mapping studies identified a region of homozygosity in all affected individua ls, narrowing the region to 14 cM, A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping, L inkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.