Molecular spectrum of β-thalassemia mutations in the admixed Venezuelan population, and their linkage to β-globin gene haplotypes

Autor:	Nathalie Gérard, Anabel Arends, Odalis García, Omar Castillo, Gilberto Gómez, Martha Bravo-Urquiola, Tsouria Berbar, Gloria García, Marycarmen Chacín, Dalia Velasquez, Rajagopal Krishnamoorthy, Silvia Montilla
Rok vydání:	2012
Předmět:	Genotype Clinical Biochemistry Population DNA Mutational Analysis beta-Globins Biology medicine.disease_cause Polymerase Chain Reaction law.invention Gene Frequency law medicine Prevalence Humans Allele education Allele frequency Genetics (clinical) Polymerase chain reaction Genetics education.field_of_study Mutation Base Sequence Genetic heterogeneity Biochemistry (medical) Haplotype beta-Thalassemia Hematology Venezuela Molecular biology Haplotypes Polymorphism Restriction Fragment Length
Zdroj:	Hemoglobin. 36(3)
ISSN:	1532-432X
Popis:	In order to establish the spectrum of β-thalassemia (β-thal) mutations in the Venezuelan population for the first time, 127 unrelated subjects either with a suspicion of β-thal trait or with a clinically recognized β-thal syndrome of different degrees of severity, were studied. DNA from these subjects was analyzed by a polymerase chain reaction (PCR)-based reverse dot-blot method or amplification refractory mutation system (ARMS). Prototype β-globin gene sequencing of relevant DNA was performed to confirm the mutations. Fifteen different mutations were identified accounting for 92.0% of the mutant alleles explored, revealing a significant genetic heterogeneity at the β-globin gene locus in this population. The most frequent mutations were codon 39 (C >T) 34.1%, IVS-I-1 (G >A) 11.1%, IVS-I-6 (T > C) 6.6%, IVS-I-110 (G >A) 6.6%, IVS-II-849 (A >G) 6.6%, -88 (C >T) 6.0%, -29 (A >G) 5.2%, followed by the less common IVS-I-5 (G >A) 3.7%, the 1,393 bp deletion 3.0%, IVS-II-1 (G >A) 3.0%, -86 (C >G) 2.2%, IVS-II-1 (G >T) 1.5%, codons 41/42 (-TCTT) 1.5%, IVS-II-745 (C >G) 0.7% and deletional δβ-thal 0.7%. Overall, these data demonstrate that the major sources of β-thal alleles in Venezuela, as expected, are of Mediterranean and African origins. This is the first large study defining the molecular spectrum of β-thal in the highly admixed population of Venezuela and lays the foundation for genetic counseling as well as implementing comprehensive clinical care programs. Diversity of haplotypes associated with some of the β-thal mutations can be explained by in situ recombination events in Venezuela.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0447ff0d465818453f54b6def5f6937f https://pubmed.ncbi.nlm.nih.gov/22563936 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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