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Gaucher disease: the origins of the Ashkenazi Jewish N370S and 84GG acid beta-glucosidase mutations

2000-06Journal article Open access
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dc.contributor.authorDiaz, G.A.
dc.contributor.authorGelb, B.D.
dc.contributor.authorRisch, N.
dc.contributor.authorNygaard, T.G.
dc.contributor.authorFrisch, A.
dc.contributor.authorCohen, I.J.
dc.contributor.authorMiranda, C.S.
dc.contributor.authorAmaral, O.
dc.contributor.authorMaire, I.
dc.contributor.authorPoenaru, L.
dc.contributor.authorCaillaud, C.
dc.contributor.authorWeizberg, M.
dc.contributor.authorMistry, P.
dc.contributor.authorDesnick, R.J.
dc.date.accessioned2011-10-28T13:11:19Z
dc.date.available2011-10-28T13:11:19Z
dc.date.issued2000-06
dc.description.abstractType 1 Gaucher disease (GD), a non-neuronopathic lysosomal storage disorder, results from the deficient activity of acid beta-glucosidase (GBA). Type 1 disease is panethnic but is more prevalent in individuals of Ashkenazi Jewish (AJ) descent. Of the causative GBA mutations, N370S is particularly frequent in the AJ population, (q approximately .03), whereas the 84GG insertion (q approximately .003) occurs exclusively in the Ashkenazim. To investigate the genetic history of these mutations in the AJ population, short tandem repeat (STR) markers were used to map a 9.3-cM region containing the GBA locus and to genotype 261 AJ N370S chromosomes, 60 European non-Jewish N370S chromosomes, and 62 AJ 84GG chromosomes. A highly conserved haplotype at four markers flanking GBA (PKLR, D1S1595, D1S2721, and D1S2777) was observed on both the AJ chromosomes and the non-Jewish N370S chromosomes, suggesting the occurrence of a founder common to both populations. Of note, the presence of different divergent haplotypes suggested the occurrence of de novo, recurrent N370S mutations. In contrast, a different conserved haplotype at these markers was identified on the 84GG chromosomes, which was unique to the AJ population. On the basis of the linkage disequilibrium (LD) delta values, the non-Jewish European N370S chromosomes had greater haplotype diversity and less LD at the markers flanking the conserved haplotype than did the AJ N370S chromosomes. This finding is consistent with the presence of the N370S mutation in the non-Jewish European population prior to the founding of the AJ population. Coalescence analyses for the N370S and 84GG mutations estimated similar coalescence times, of 48 and 55.5 generations ago, respectively. The results of these studies are consistent with a significant bottleneck occurring in the AJ population during the first millennium, when the population became established in Europe.por
dc.description.sponsorshipNIH and FCT fellowshipspor
dc.identifier.citationAm J Hum Genet. 2000 Jun;66(6):1821-32. Epub 2000 Apr 21por
dc.identifier.issn0002-9297
dc.identifier.otherdoi:10.1086/302946
dc.identifier.urihttp://hdl.handle.net/10400.18/302
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevier (Cell Press)por
dc.relationFCT BD/5547/95por
dc.relation.publisherversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378046/pdf/10777718.pdfpor
dc.subjectDoenças Genéticaspor
dc.subjectGenética populacionalpor
dc.subjectGaucher Diseasepor
dc.subjectGenética Humanapor
dc.subjectHaplotypepor
dc.subjectEuropepor
dc.subjectJews geneticspor
dc.subjectFounder effectpor
dc.titleGaucher disease: the origins of the Ashkenazi Jewish N370S and 84GG acid beta-glucosidase mutationspor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1832por
oaire.citation.startPage1821por
oaire.citation.titleAmerican Journal of Human Geneticspor
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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