[Colombian haplotypes of the Gaucher disease-causing N370S mutation may originate from a possible common ancestral haplotype].
BACKGROUND
Gaucher disease is a pan-ethnic condition characterised by glucosylceramide accumulation in macrophages due to glucocerebrosidase deficiency. Its gene, GBA, has been mapped to 1q21 and mutation N370S is the main cause of the disease in western populations, including Colombia.


OBJECTIVE
To asses the degree of association between N370S mutation and the alleles of five microsatellites near the mutation site in the GBA locus in nine Colombian Gaucher patients, from the Cundinamarca-Boyacá region.


METHODS
DNA from patients bearing the N370S mutation, their closest relatives, and 30 controls was taken to PCR-amplify the markers: D1S305, D1S2624, DIS2777, ITG6.6.2 and 5GC3.2. Allele frequencies were calculated, haplotypes inferred and linkage disequilibrium levels between marker alleles and N370S were also estimated.


RESULTS
Eleven N370S chromosomes were obtained. A consensus N370S haplotype consisting of the alleles: 222-314-260-301-172 (base pairs) was identified. Each allele corresponding to markers 5GC3.2, ITG6.6.2, D1S277, D1S2624 and D1S305, respectively. There was statistically significant linkage disequilibrium between the alleles of 222, 314, 260, 301 base pairs and the N370S mutation.


CONCLUSIONS
A conserved fraction of the haplotypes suggests that N370S may be present among patients and stem from a single ancestral chromosome for which the ethnic origin is still unclear.
Wilches
Ricardo
R
Instituto de Errores Innatos del Metabolismo, Facultad de Ciencias, Pontifica Universidad Javeriana, Bogotá D.C., Colombia.
Vega
Hugo
H
Echeverri
Olga
O
Barrera
Luis Alejandro
LA
D003105:Colombia; D005776:Gaucher Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D009154:Mutation