title: Analysis of delta-globin gene mutations in Greek cypriots.
abstract: We recently described four delta-globin gene mutations in Greek Cypriots studied by polymerase chain reaction (PCR) amplification and automated fluorescence-based DNA sequence analysis (Blood 78:3298, 1991). Selective restriction enzyme digestion of PCR products facilitated direct mutation detection. Twenty-eight additional samples from unrelated Cypriots with Hb A2 levels ranging from 0.6% to 3.6% were studied by PCR and showed the following: twelve had the delta 27 (ala-->ser) mutation, one was heterozygous for the delta IVS-2 AG-->GG change, and none had either the delta 116 (arg-->cys) or delta 141 (leu-->pro) mutations. The remaining samples were divided into two groups: 11 with borderline normal Hb A2 values that were not pursued; and four with abnormal Hb A2 values. The delta-globin genes from these four samples were sequenced and the same four changes identified in each: a C-->T at -199, a C-->T at codon 4 (thr-->ile), a silent C-->T at codon 97, and an AT deletion at position 722 in IVS-2. The codon 4 change abolishes a Ple I site whereas the codon 97 creates an Nla III site, thus facilitating rapid identification. All four changes are in cis position, suggesting that the -199 C-->T, the C-->T at codon 97, and the AT deletion in IVS-2 are neutral polymorphisms present on the codon 4 (thr-->ile) chromosome. DNA haplotype analysis suggests all five delta-globin gene mutant alleles arose independently on different chromosomal backgrounds.
authors.affiliation: Biomedical Graduate Studies, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: P
authors.initials: P
authors.lastname: Trifillis
authors.forename: A
authors.initials: A
authors.lastname: Kyrri
authors.forename: E
authors.initials: E
authors.lastname: Kalogirou
authors.forename: A
authors.initials: A
authors.lastname: Kokkofitou
authors.forename: P
authors.initials: P
authors.lastname: Ioannou
authors.forename: E
authors.initials: E
authors.lastname: Schwartz
authors.forename: S
authors.initials: S
authors.lastname: Surrey
mesh_terms: D001483:Base Sequence; D003535:Cyprus / Q000208:ethnology; D005914:Globins / Q000235:genetics*; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D013789:Thalassemia / Q000235:genetics
chemical_list: D005914:Globins