GENETIC FINE LOCALIZATION OF THE BETA-GLUCOCEREBROSIDASE (GBA) AND PROSAPOSIN (PSAP) GENES - IMPLICATIONS FOR GAUCHER-DISEASE

Mutations in the glucocerebrosidase (GBA) and prosaposin (PSAP) genes are responsible for Gaucher disease, the most prevalent sphingolipidos is. Somatic cell hybrid analysis and in situ hybridization experiments have localized the GBA gene to 1q21 and the PSAP gene to 10q21-q22. W e performed pairwise and multi-point linkage analyses between the two genes and several highly polymorphic markers from the Genethon human l inkage map. Our results show that six markers cosegregate with the GBA gene (Z(max) = 8.73 at theta = 0.00 for marker D1S2714) and define a 3.2-cM interval between D1S305 and D1S2624 as the most probable locati on for the gene. Three of these markers (D1S2777, D1S303, and D1S2140) , as well as the gene encoding pyruvate kinase (PKLR), are contained i n a single YAC clone together with the GBA gene. A new polymorphism wa s identified within the PSAP gene (C16045T) and used for linkage studi es. The multi-point analysis places the gene in a 9.8-cM interval betw een D10S1688 and D10S607. The fine localization of these genes provide s a useful tool for cosegregation analysis, indirect molecular diagnos is, and population genetic studies.