Repositório Científico do Instituto Nacional de Saúde >
Departamento de Genética Humana >
DGH - Artigos em revistas internacionais >

Please use this identifier to cite or link to this item:

Título: Gaucher disease: the origins of the Ashkenazi Jewish N370S and 84GG acid beta-glucosidase mutations
Autor: Diaz, G.A.
Gelb, B.D.
Risch, N.
Nygaard, T.G.
Frisch, A.
Cohen, I.J.
Miranda, C.S.
Amaral, O.
Maire, I.
Poenaru, L.
Caillaud, C.
Weizberg, M.
Mistry, P.
Desnick, R.J.
Palavras-chave: Doenças Genéticas
Genética populacional
Gaucher Disease
Genética Humana
Jews genetics
Founder effect
Issue Date: Jun-2000
Editora: Elsevier (Cell Press)
Citação: Am J Hum Genet. 2000 Jun;66(6):1821-32. Epub 2000 Apr 21
Resumo: Type 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.
Arbitragem científica: yes
ISSN: 0002-9297
Versão do Editor:
Appears in Collections:DGH - Artigos em revistas internacionais

Files in This Item:

File Description SizeFormat
Gaucher Disease_The Origins of the Ashkenazi Jewish.pdf243,5 kBAdobe PDFView/Open

Please give feedback about this item
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpaceOrkut
Formato BibTex mendeley Endnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.


  © 2010 - Todos os direitos reservados | Feedback Ministério da Saúde
Promotores do RCAAP   Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência PO Sociedade do Conhecimento (POSC) Portal oficial da União Europeia