Mapping of recombinants near the Huntington disease locus by using G8 (D4S10) and newly isolated markers in the D4S10 region.

Genetic linkage between the marker G8 (D4S10) and Huntington disease (HD) was studied in six Dutch pedigrees. The informativeness of the D4S10 locus was increased by isolation of a cosmid, C5.5, with a G8 subclone used as probe. We present a restriction map of 70 kb in the D4S10 region. Two subclones of C5.5, H5.52 and F5.53, detect MspI and SinI RFLPs, respectively. These probes increase the informativeness of D4S10 in the Dutch HD population from 55% to 95%. Seven recombinations were found in 124 informative meioses in which multipoint segregation of D4S10 haplotypes and the HD locus was studied. Two of the recombinations occurred within the D4S10 region. The other five recombinations are highly valuable for the mapping of present and future markers relative to each other and to the HD gene. In addition, several recombinations between markers in meioses from unaffected parents were noted, which will also be useful in ordering new markers. On the basis of our three-point recombination data, the orientation of the D4S10 region relative to HD is HD-H5.52-G8-F5.53, which independently confirms the previously derived polarity for D4S10.