RESUMO
We have sequenced the complete mtDNA of a family with hypertension (HT), type 2 diabetes (T2D) and coronary artery disease (CAD). Our analysis revealed two novel mutations (C3519T, G13204A); of which G13204A replaces valine to isoleucine. In silico analysis of a rare missense mutation (T8597C) showed a deleterious effect. We also observed a 50bp deletion (m.298_347del50) in the hypervariable region II (HVSII) of all the individuals, who had a common maternal lineage. This (50bp) deletion was not found in 17,785 individuals from different ethnic populations of India or in a variety of different disease phenotypes. We predict that the mtDNA mutations might be responsible for the HT. Analysis of POLG (polymerase gamma) gene revealed 14 variants which might be responsible for some of the mtDNA mutations seen in this family.
Assuntos
DNA Mitocondrial/genética , Saúde da Família , Genoma Mitocondrial , Hipertensão/genética , Mutação Puntual , Deleção de Sequência , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , DNA Polimerase gama , DNA Mitocondrial/química , DNA Polimerase Dirigida por DNA/genética , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNARESUMO
The dopamine transporter (DAT1) is a membrane spanning protein that binds the neurotransmitter dopamine and performs re-uptake of dopamine from the synapse into a neuron. The gene encoding DAT1 consists of 15 exons spanning 60 kb on chromosome 5p15.32. Several studies have investigated the possible associations between variants in DAT1 gene and psychiatric disorders. The present study aimed to determine the distribution of the variable number of tandem repeat (VNTR) polymorphism in the 3' untranslated region of DAT1 in 12 Indian populations. A total of 471 healthy unrelated individuals in 12 Indian populations from 3 linguistic groups were included in the present study. The analysis was carried out using PCR and electrophoresis. Overall, 4 alleles of the DAT1 40-bp VNTR, ranging from 7 to 11 repeats were detected. Heterozygosity indices were low and varied from 0.114 to 0.406. The results demonstrate the variability of the DAT1 40-bp VNTR polymorphism in Indian populations and revealed a high similarity with East Asian populations.
