title: Genetic fine localization of the beta-glucocerebrosidase (GBA) and prosaposin (PSAP) genes: implications for Gaucher disease.
abstract: Mutations in the glucocerebrosidase (GBA) and prosaposin (PSAP) genes are responsible for Gaucher disease, the most prevalent sphingolipidosis. Somatic cell hybrid analysis and in situ hybridization experiments have localized the GBA gene to 1q21 and the PSAP gene to 10q21-q22. We performed pairwise and multi-point linkage analyses between the two genes and several highly polymorphic markers from the Généthon human linkage map. Our results show that six markers cosegregate with the GBA gene (Zmax = 8.73 at theta = 0.00 for marker D1S2714) and define a 3.2-cM interval between D1S305 and D1S2624 as the most probable location for the gene. Three of these markers (D1S2777, D1S303, and D1S2140), as well as the gene encoding pyruvate kinase (PKLR), are contained in a single YAC clone together with the GBA gene. A new polymorphism was identified within the PSAP gene (C16045T) and used for linkage studies. The multi-point analysis places the gene in a 9.8-cM interval between D10S1688 and D10S607. The fine localization of these genes provides a useful tool for cosegregation analysis, indirect molecular diagnosis, and population genetic studies.
authors.affiliation: Department de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Cormand
authors.forename: M
authors.initials: M
authors.lastname: Montfort
authors.forename: A
authors.initials: A
authors.lastname: Chabás
authors.forename: L
authors.initials: L
authors.lastname: Vilageliu
authors.forename: D
authors.initials: D
authors.lastname: Grinberg
mesh_terms: D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005776:Gaucher Disease / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D005962:Glucosylceramidase / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D011110:Polymorphism, Genetic; D011498:Protein Precursors / Q000235:genetics; D015183:Restriction Mapping; D049231:Saposins
chemical_list: D005819:Genetic Markers; D006023:Glycoproteins; C483345:PSAP protein, human; D011498:Protein Precursors; D049231:Saposins; D005962:Glucosylceramidase