MAP REFINEMENT OF LOCUS RP13 TO HUMAN-CHROMOSOME 17P13.3 IN A 2ND FAMILY WITH AUTOSOMAL-DOMINANT RETINITIS-PIGMENTOSA

In order to elucidate the genetic basis of autosomal dominant retiniti s pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British descent, we assessed linkage between the UCLA-RP09 adRP gene a nd numerous genetic loci, including eight adRP candidate genes, five a nonymous adRP-linked DNA loci, and 20 phenotypic markers. Linkage to t he UCLA-RP09 disease gene was excluded for all eight candidate genes a nalyzed, including rhodopsin (RP4) and peripherin/RDS (RP7), for the f our adRP loci RP1, RP9, RP10 and RP11, as well as for 17 phenotypic ma rkers. The anonymous DNA marker locus D17S938, linked to adRP locus RP 13 on chromosome 17p13.1, yielded a suggestive but not statistically s ignificant positive lod score. Linkage was confirmed between the UCLA- RP09 adRP gene and markers distal to D17S938 in the chromosomal legion 17p13.3. A reanalysis of the original RP13 data from a South African adRP family of British descent, in conjunction with our UCLA-RP09 data , suggests that only one adRP locus exists on 17p but that it maps to a more telomeric position, at band 17p13.3, than previously reported. Confirmation of the involvement of RP13 in two presumably unrelated ad RP families, both of British descent, suggests that this locus is a di stinct adRP gene in a proportion of British, and possibly other, adRP families.