Heterogeneity of the epsilon gamma delta beta-thalassaemias: characterization of three novel English deletions.
We have characterized three novel epsilon gamma delta beta-thalassaemia deletions in three English families. Two of the deletions, 114 and 439 kb, removed the entire beta-globin gene complex, including a variable number of flanking olfactory receptor (HOR) genes. The 98-kb deletion extended 90-kb upstream of the epsilon gene to 8 kb upstream of the G gamma-gene, leaving the gamma,delta and beta-genes intact. The 439 kb deletion is the largest deletion reported so far to cause epsilon gamma delta beta-thalassaemia; heterozygotes for this deletion were variably affected by neonatal haemolytic anaemia. Two of the deletions were de novo. Breakpoints of all three deletions occurred within regions of L1 or Alu repeats and contained short regions of direct homology between the flanking sequences, a feature that is likely to have contributed to the illegitimate recombinations.
Rooks
Helen
H
Department of Haematological Medicine, Guy's Kings' & St Thomas' School of Medicine, King's College London, London SE5 9PJ, UK.
Bergounioux
Jean
J
Game
Laurence
L
Close
James Paul
JP
Osborne
Cameron
C
Best
Steve
S
Senior
Tania
T
Height
Susan
S
Thompson
Richard
R
Hadzic
Nedim
N
Fraser
Peter
P
Bolton-Maggs
Paula
P
Thein
Swee Lay
SL
D000745:Anemia, Hemolytic, Congenital / Q000145:classification* / Q000235:genetics; D002648:Child; D017353:Gene Deletion; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D017422:Sequence Analysis, DNA; D017086:beta-Thalassemia / Q000145:classification* / Q000235:genetics*
D005914:Globins