RESUMO
In search of genetic alterations responsible for high fetal hemoglobin (Hb F) phenotypes in the population of eastern India, 91 probands were screened for four polymorphisms by sequencing and/or restriction fragment length polymorphism (RFLP) analysis. These are the A>G allele on the rs4895441 locus in the intergenic region between HBS1L and MYB on chromosome 6, the G>A allele on the rs4671393 locus on chromosome 2 (BCL11A gene), the A>C allele on the rs2071348 (HBBP1 gene) and the XmnI polymorphism (rs7482144, -158 position of HBG2) on chromosome 11. We found a significant association (p = 0.002 and 0.0013) of Hb F levels with rs2071348 and rs4895441, respectively. However, the polymorphism rs4671393 gene did not show significant association with Hb F levels (p = 0.0655). As is well known, the XmnI polymorphism (p <0.0001) showed the strongest association.
Assuntos
Proteínas de Transporte/genética , Hemoglobina Fetal/metabolismo , Genes myb , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , gama-Globinas/genética , Adolescente , Adulto , Anemia Falciforme/genética , Anemia Falciforme/metabolismo , Criança , Pré-Escolar , DNA Intergênico , Feminino , Humanos , Índia , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Polimorfismo Genético , Proteínas Repressoras , Adulto Jovem , Globinas beta/genéticaRESUMO
Point mutations of alpha-globin genes in homozygous or in compound heterozygous states cause severe alpha-thalassemia (alpha-thal). Here we describe a polymerase chain reaction-restriction fragment length polymorphism-based method for easy detection of the point mutation Hb Sallanches [alpha104(G11)Cys-->Tyr, TGC>TAC], earlier detected by a sequencing technique. In a cohort of 104 unrelated putative alpha-thal patients, nine carried the mutation and two were homozygotes. The mutation occurred on both the alpha2- or alpha1-globin genes. The phenotypes, in conjunction with other point mutations or deletions, are presented. Earlier detected in Pakistan and Punjab of India, it is probably present all over the Indian subcontinent.
Assuntos
Hemoglobinas Anormais/genética , Talassemia alfa/genética , Frequência do Gene , Humanos , Incidência , Índia/epidemiologia , Fenótipo , Mutação Puntual , Polimorfismo de Fragmento de RestriçãoRESUMO
We have used restriction site-dependent polymerase chain reaction (PCR)-based methodology for detection of the alpha-globin polyadenylation (poly A) signal mutation, AATAAA>AATA- - and Hb Sun Prairie [alpha 130(H13)Ala-->Pro, GCT>CCT (alpha2)] mutation. The former mutation produces Hb H disease in the homozygous state and occurs frequently in the Indian population. It was detected in nine of 77 putative alpha-thalassemia (alpha-thal) patients and in three of 13 beta-thal intermedia patients tested. Four of the nine alpha-thal patients were homozygotes for the mutation. The Hb Sun Prairie mutation was confirmed in two alpha-thal patients, one of whom was a homozygote and the other a heterozygote.
Assuntos
Hemoglobinas Anormais/genética , Mutação , alfa-Globinas/genética , Talassemia alfa/genética , Talassemia beta/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Frequência do Gene , Testes Genéticos , Humanos , Índia , Lactente , Reação em Cadeia da Polimerase/métodos , Adulto JovemRESUMO
We have detected, in three unrelated eastern Indian individuals, a hitherto unreported alpha zero deletion, - -KOL, in the heterozygous state, encompassing the embryonic zeta2-globin and the duplicated alpha-globin genes extending from c. 1150 bp upstream of the zeta2 globin gene to c. 960 bp downstream of the theta1 gene. Other deletions present in 120 unrelated, eastern Indian, putative alpha-thalassaemia patients are -3.7 kb (16.25%), -4.2 kb (5%) and - -SEA (3.33%).
