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A novel deletion causing (εγδβ)° thalassaemia in a Chilean family
Author(s) -
Game Laurence,
Bergounioux Jean,
Close James Paul,
Marzouka B. Esperenza,
Thein Swee Lay
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04564.x
Subject(s) - genetics , breakpoint , biology , gene , gene cluster , deletion mapping , homologous recombination , direct repeat , microbiology and biotechnology , chromosomal translocation , genome , chromosome
Summary. We describe a novel deletion causing (εγδβ)° thalassaemia segregating in three generations of a Chilean family of Spanish descent. Heterozygotes for the deletion were all affected by neonatal haemolytic anaemia. The deletion of 152,569 bp extends from 77 kb upstream of the ε gene to 31 kb downstream of the β gene, and includes the entire β‐globin gene cluster and two upstream olfactory receptor genes. Comparison of the sequences of the deletion junction with those of the flanking normal DNA suggests that the deletion results from a non‐homologous recombination event. The insertion of 16 ‘orphan’ nucleotides in the deletion junction creates a perfect inverted repeat of 12 nucleotides, forming a 12‐bp stem with a four‐nucleotide loop that could have contributed to the illegitimate recombination. The 3′ breakpoint is located within an L1 family repeat that contains a perfect 160‐bp palindrome, and is in close proximity to the 3′ breakpoints of five other deletions in the β cluster – Indian (HPFH‐3), Italian (HPFH‐4) and Vietnamese GγAγ (δβ)° HPFH, German and Belgian Gγ (Αγδβ)° thalassaemia.