A somatic cell hybrid panel for localizing DNA segments near the Huntington's disease gene

Abstract

Thirty-four random DNA probes from the terminal half of the human chromosome 4 short arm were further localized within 4pter----p15.1. A panel of somatic cell hybrid lines defining six chromosomal regions within 4pter----p15.1 was constructed using human cell lines containing translocation or deletion chromosomes. The vast majority of the DNA sequences, 32 of 34 or 94%, mapped to the three most proximal regions comprising 4p16.1----4p15.1. Only two probes were localized distal to 4p16.1: one in the region 4p16.3----4p16.1 and one in 4p16.3. D4S10, a polymorphic DNA marker linked to the Huntington's disease defect, has previously been mapped to the terminal region of 4p with conflicting assignments to 4p16.1 and 4p16.3. Analysis of restriction fragment length polymorphisms demonstrated hemizygosity for D4S10 in a patient with Wolf-Hirschhorn syndrome resulting from an unbalanced translocation t(4;8)(p16.3;p23.1), supporting the 4p16.3 localization. Our panel of somatic cell hybrids provides a rapid method for mapping new probes to the same vicinity as that of D4S10. However, the relative paucity of such DNA segments identified here suggests that a more directed approach may be required to generate additional markers near the HD gene.