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: Novel large deletions in the human alpha-globin gene cluster: Clarifying the HS-40 long-range regulatory role in the native chromosome environment
Autor: Coelho, Andreia
Isabel, Picanço
Filomena, Seuanes
Seixas, Maria Teresa
Paula, Faustino
Palavras-chave: α-thalassemia
Large deletion
α-globin gene cluster
Doenças Genéticas
Patologias do Glóbulo Vermelho
Issue Date: 15-Aug-2010
Editora: Elsevier
Citação: Blood Cells Mol Dis. 2010 Aug 15;45(2):147-53. Epub 2010 Jun 30
Resumo: Globin genes, which encode the protein subunits of hemoglobin (Hb), are organized in two different gene clusters and present a coordinated and differential pattern of expression during development. Concerning the human α-globin gene cluster (located at chromosome region 16p13.3), four upstream highly conserved elements known as multispecies conserved sequences (MCS-R1-4) or DNase I hypersensitive sites (HSs) are implicated in the long-range regulation of downstream gene expression. However, only the absence of the MCS-R2 site (HS-40) has proven to drastically downregulate the expression of those genes, and consequently, it has been regarded as the major and crucial distal regulatory element. In this study, Multiplex Ligation-dependent Probe Amplification was used to screen for deletions in the telomeric region of the short arm of chromosome 16, in an attempt to explain the α-thalassemia or the HbH disease present in a group of Portuguese patients. We report four novel and five uncommon deletions that remove the α-globin distal regulatory elements and/or the complete α-globin gene cluster. Interestingly, one of them occurred de novo and removes all HSs except HS-10, while other eliminates only the HS-40 site, the latter being replaced by the insertion of a 39 nucleotide orphan sequence. Our results demonstrate that HS-10 alone does not significantly enhance the α-globin gene expression. The absence of HS-40 in homozygosity, found in a patient with Hb H disease, strongly downregulates the expression of α-globin genes but it is not associated with a complete absence of α-globin chain production. The study of naturally occurring deletions in this region is of great interest to understand the role of each upstream regulatory element in the native human erythroid environment.
Arbitragem científica: yes
ISSN: 1079-9796
Appears in Collections:DGH - Artigos em revistas internacionais
DPSPDNT - Artigos em revistas internacionais

Files in This Item:

File Description SizeFormat
Novel large deletions in the human.pdf502,88 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