Linkage analysis of human chromosome 4: exclusion of autosomal dominant retinitis pigmentosa (ADRP) and detection of new linkage groups

Abstract

As part of our ongoing linkage studies of degenerative retinal diseases, we tested seven DNA markers and two classical genetic markers from chromosome 4 in two extended families with autosomal dominant retinitis pigmentosa (ADRP). Our goals were (1) to detect or exclude linkage of ADRP to markers spanning most of chromosome 4 and (2) to contribute useful new information regarding the linkage map of this chromosome. Our results exclude linkage of ADRP from more than 82% of chro mosome 4. We detected four new linkage relationships: loose linkage of K082 (D4S10) and G1E5 (D4S21) at a distance of 21 cM; loose linkage of 4F2 (D4S18) and GC protein at a distance of 19 cM; tight linkage (i.e., no recombinants) between B3D (D4S44), B5A (D4S40), and the MNS blood group; and tight linkage between 4F2 and GDS5 (D4S23). These data, combined with previously reported data, exclude ADRP from approximately 35% of the human genome.

Metabolic and Redox Signaling of the Nucleoredoxin-Like-1 Gene for the Treatment of Genetic Retinal Diseases

“…The identification of the first mutation causing RP in human left the scientific community perplexed. After having localized the gene on a short interval of the long arm of chromosome 3, a dominant mutation in the gene encoding for the rhodopsin, the visual pigment of rods, was identified [73][74][75]. Electroretinogram (ERG) measurements of affected members of this pedigree confirmed that RP progresses from an early abnormal rod response to a subsequent altered cone response.…”

Retinal degenerations of hereditary, viral and autoimmune origins: Studies on opsin and IRBP

“…It was not until 1989, though, that linkage studies on a family with ADRP made it apparent that a candidate gene approach to the study of the RP family of diseases was warranted. Humphries and his collaborators, as recently reviewed in this series (Humphries et al, 1993) had been working on a large Irish pedigree with ADRP for some time Daiger et al, 1989) and found that the anonymous DNA marker D3S47 tightly segregated with the disease phenotype in this family . The lod score calculated for the coinheritance of D3S47 and the ADRP disease gene was 14.7, an exceedingly high value which gave strong evidence for the locus of the disease on the long arm of chromosome 3 (i.e.…”