LOCALIZATION OF THE KRABBE DISEASE GENE (GALC) AN CHROMOSOME-14 BY MULTIPOINT LINKAGE ANALYSIS

The gene responsible for Krabbe disease, an autosomal recessive disord er caused by deficiency of galactocerebrosidase (GALC), was localized by multipoint linkage analysis on chromosome 14. Eight mapped dinucleo tide repeat polymorphisms were tested for linkage to GALC. Two-point l inkage analysis demonstrated close linkage of GALC and D14S48, with (Z ) over cap = 13.63 at <(theta)over cap> = 0. Multipoint analysis yield ed strong support for this finding, with maximum likelihood for GALC l ocated within 1 cM of D14S48. This analysis also identified markers th at clearly flank the GALC locus, as the map order of D14S53-GALC-D14S4 5 is favored by odds greater than 10(6):1. Additional support for clos e linkage of GALC and D14S48 comes from the apparent linkage disequili brium between these two loci in a consanguineous Druze community in Is rael. These data localize GALC to 14q24.3-q32.1.