A NOVEL GENE CONTAINING A TRINUCLEOTIDE REPEAT THAT IS EXPANDED AND UNSTABLE ON HUNTINGTONS-DISEASE CHROMOSOMES

作者：MACDONALD ME; AMBROSE CM; DUYAO MP; MYERS RH; LIN C; SRINIDHI L; BARNES G; TAYLOR SA; JAMES M; GROOT N; MACFARLANE H; JENKINS B; ANDERSON MA; WEXLER NS; GUSELLA JF; BATES GP; BAXENDALE S; HUMMERICH H; KIRBY S; NORTH M; YOUNGMAN S; MOTT R; ZEHETNER G; SEDLACEK Z; POUSTKA A; FRISCHAUF AM; LEHRACH H; BUCKLER AJ; CHURCH D; DOUCETTESTAMM L; ODONOVAN MC; RIBARAMIREZ L; SHAH M; STANTON VP; STROBEL SA; DRATHS KM; WALES JL; DERVAN P; HOUSMAN DE; ALTHERR M

来源：Cell, 1993, 72(6): 971-983.

DOI：10.1016/0092-8674(93)90585-E

The Huntington's disease (HD) gene has been mapped in 4p16.3 but has eluded identification. We have used haplotype analysis of linkage disequilibrium to spotlight a small segment of 4p16.3 as the likely location of the defect. A new gene, IT15, isolated using cloned trapped exons from the target area contains a polymorphic trinucleotide repeat that is expanded and unstable on HD chromosomes. A (CAG)n repeat longer than the normal range was observed on HD chromosomes from all 75 disease families examined, comprising a variety of ethnic backgrounds and 4p16.3 haplotypes. The (CAG)n repeat appears to be located within the coding sequence of a predicted approximately 348 kd protein that is widely expressed but unrelated to any known gene. Thus, the HD mutation involves an unstable DNA segment, similar to those described in fragile X syndrome, spino-bulbar muscular atrophy, and myotonic dystrophy, acting in the context of a novel 4p16.3 gene to produce a dominant phenotype.

• 出版日期1993-3-26
• 单位河北医科大学