A LINKAGE STUDY WITH DNA MARKERS (D4S95, D4S115, AND D4S111) IN JAPANESE HUNTINGTON DISEASE FAMILIES

作者：WATANABE M; KONDO I; NISSATO S; WAKISAKA A; TODA T; IKEDA J; WASMUTH JJ; GUSELLA JF; KANAZAWA I

来源：Japanese Journal of Human Genetics, 1993, 38(2): 193-201.

DOI：10.1007/BF01883710

• HUNTINGTON DISEASE
• LINKAGE ANALYSIS
• D4S95
• D4S115
• D4S111

Attempts to isolate the Huntington disease (HD) gene based on its position have been frustrated by apparently contradictory recombination events in HD pedigrees that have predicted two non-overlapping candidate regions: 100 kb at the telomere of the short arm of chromosome 4, and a 2.2 Mb region located internally at 4p16.3. The proximal location is also supported by the detection of a linkage disequilibrium between HD and some restriction fragment length polymorphisms (RFLPs) at the D4S95, D4S98, and D4S127 loci. In the present study, a proximal marker D4S95 showed tight linkage to the disease locus in Japanese pedigrees (Z(max)=3.31, theta(max)=0.00), while distal markers D4S115 and D4S111 did not. Particularly, a two point linkage analysis between D4S111 and HD yielded a lod score - 2.01 for theta = 0.015. This result leads to the exclusion, as a possible region of localization of the HD gene, of more than 3 cM of the genome around D4S111 locus. At the same ti me our results favor aforementioned proximal location as a candidate location for the HD gene.

• 出版日期1993-6