Details

Autor(en) / Beteiligte

• Viprakasit, Vip
• Kidd, Alexa M. J.
• Ayyub, Helena
• Horsley, Sharon
• Hughes, Jim
• Higgs, Douglas R.

Titel

De novo deletion within the telomeric region flanking the human α globin locus as a cause of α thalassaemia

Ist Teil von

• British journal of haematology, 2003-03, Vol.120 (5), p.867-875

Ort / Verlag

Oxford, UK: Blackwell Science Ltd

Erscheinungsjahr

2003

Quelle

Wiley

Beschreibungen/Notizen

• We have identified and characterized a Scottish individual with α thalassaemia, resulting from a de novo 48 kilobase (kb) deletion from the telomeric flanking region of the α globin cluster which occurred as a result of recombination between two misaligned repetitive elements that normally lie ∼83 kb and 131 kb from the 16p telomere. The deletion removes two previously described putative regulatory elements (HS‐40 and HS‐33) but leaves two other elements (HS‐10 and HS‐8) intact. Analysis of this deletion, together with eight other published deletions of the telomeric region, showed that they all severely downregulated α globin expression. Together they defined a 20·4‐kb region of the human α cluster, which contains all of the positive cis‐acting elements required to regulate α globin expression. Comparative analysis of this region with the corresponding segment of the mouse α globin cluster demonstrated conserved non‐coding sequences corresponding to the putative regulatory elements HS‐40 and HS‐33. Although the role of HS‐40 as an enhancer of α globin expression is fully established, these observations suggest that the role of HS‐33 and other sequences in this region should be more fully investigated in the context of the natural human and mouse α globin loci.