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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Linkage of the PvuII polymorphism with the common Jewish mutation for Gaucher disease
A Zimran1, T Gelbart, E Beutler
1Scripps Clinic and Research Foundation, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Abstract:
We have localized the PvuII polymorphism of the glucocerebrosidase gene complex to intron 6 of the active gene. Using the polymerase chain reaction (PCR) to amplify intron 6 of DNA samples from Pv1.1-/Pv1.1+ individuals, we defined the mutation causing this polymorphism as a G----A single-base substitution at position 3931 of the active gene. By analyzing 54 unrelated Gaucher patients we show strong linkage disequilibrium between the Pv1.1- genotype and the common Jewish mutation 1226 causing the adult type of this disease. Gaucher disease patients heterozygous for the 1226 allele and one unidentified allele (1226/?), particularly those of Jewish ancestry, were predominantly of the Pv1.1-/PV1.1+ genotype. This suggests that one of the unknown alleles may be relatively common and linked to the Pv1.1+ genotype.
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