title: Investigation of mutations in the HBB gene using the 1,000 genomes database.
abstract: Mutations in the HBB gene are responsible for several serious hemoglobinopathies, such as sickle cell anemia and β-thalassemia. Sickle cell anemia is one of the most common monogenic diseases worldwide. Due to its prevalence, diverse strategies have been developed for a better understanding of its molecular mechanisms. In silico analysis has been increasingly used to investigate the genotype-phenotype relationship of many diseases, and the sequences of healthy individuals deposited in the 1,000 Genomes database appear to be an excellent tool for such analysis. The objective of this study is to analyze the variations in the HBB gene in the 1,000 Genomes database, to describe the mutation frequencies in the different population groups, and to investigate the pattern of pathogenicity. The computational tool SNPEFF was used to align the data from 2,504 samples of the 1,000 Genomes database with the HG19 genome reference. The pathogenicity of each amino acid change was investigated using the databases CLINVAR, dbSNP and HbVar and five different predictors. Twenty different mutations were found in 209 healthy individuals. The African group had the highest number of individuals with mutations, and the European group had the lowest number. Thus, it is concluded that approximately 8.3% of phenotypically healthy individuals from the 1,000 Genomes database have some mutation in the HBB gene. The frequency of mutated genes was estimated at 0.042, so that the expected frequency of being homozygous or compound heterozygous for these variants in the next generation is approximately 0.002. In total, 193 subjects had a non-synonymous mutation, which 186 (7.4%) have a deleterious mutation. Considering that the 1,000 Genomes database is representative of the world's population, it can be estimated that fourteen out of every 10,000 individuals in the world will have a hemoglobinopathy in the next generation.
authors.affiliation: Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil.
authors.forename: Tânia
authors.initials: T
authors.lastname: Carlice-Dos-Reis
authors.affiliation: Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil.|Federal Rural University of the Amazon, Capanema Campus, PA, Brazil.
authors.forename: Jaime
authors.initials: J
authors.lastname: Viana
authors.affiliation: Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil.|Research Center of Oncology, Federal University of Pará, Belém, PA, Brazil.
authors.forename: Fabiano Cordeiro
authors.initials: FC
authors.lastname: Moreira
authors.affiliation: Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil.
authors.forename: Greice de Lemos
authors.initials: GL
authors.lastname: Cardoso
authors.affiliation: Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil.
authors.forename: João
authors.initials: J
authors.lastname: Guerreiro
authors.affiliation: Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil.|Research Center of Oncology, Federal University of Pará, Belém, PA, Brazil.
authors.forename: Sidney
authors.initials: S
authors.lastname: Santos
authors.affiliation: Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil.|Research Center of Oncology, Federal University of Pará, Belém, PA, Brazil.
authors.forename: Ândrea
authors.identifier: http://orcid.org/0000-0001-7001-1483
authors.initials: Â
authors.lastname: Ribeiro-Dos-Santos
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D044383:Black People / Q000235:genetics; D030541:Databases, Genetic; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016415:Sequence Alignment; D044465:White People / Q000235:genetics; D055544:beta-Globins / Q000235:genetics*
chemical_list: D055544:beta-Globins