RESUMO
Malaria has been endemic in India. G6PD deficiency is known to confer resistance to malaria. Many G6PD deficiency variants, some of which are India-specific, are known to occur in high frequencies in India. This is the first systematic molecular-genetic study in multiple populations from India drawn from diverse ethnic, socio-cultural and geographical backgrounds. Resequencing of the G6PD gene was carried out in 80 males and then the polymorphic variants were genotyped in 400 individuals of both genders, drawn from 10 ethnic groups of India. Our study has identified one new exonic variant (M159I; exon-5), occurring in multiple populations, that is predicted to result in G6PD deficiency. A strong geographical sub-structuring of known G6PD variants has also been established. We have compared all available data from public-domain resources with those generated in this study to identify the nature and extent of natural selection. Our results (a) provide indication of weak negative selection, and (b) reveal signals of recent positive selection for the G6PD Orissa and G6PD Coimbra mutation bearing haplotypes. These inferences have been interpreted in the light of malarial protection to the populations that have been long exposed to plasmodium infection.
Assuntos
Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Malária , Sequência de Bases , Cromossomos Humanos X , Etnicidade/genética , Feminino , Frequência do Gene , Genes Ligados ao Cromossomo X , Variação Genética , Genótipo , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/etnologia , Haplótipos , Humanos , Imunidade Inata/genética , Índia/epidemiologia , Malária/epidemiologia , Malária/etnologia , Malária/genética , Masculino , Polimorfismo Genético , Seleção GenéticaRESUMO
The HapMap data are being widely used in human genetic studies. We show by direct resequencing of a approximately 6-kb region of chromosome 1 that the HapMap data are unreliable for this region. This region contains a recent mitochondrial (mt) DNA insertion. The HapMap data report the corresponding mtDNA variation and not the nuclear DNA variation. In view of mtDNA insertions of varying lengths throughout the human genome and considerable segmental duplications, it is necessary to use the HapMap data cautiously.
Assuntos
Cromossomos Humanos Par 1/genética , Bases de Dados Genéticas/normas , Genoma Humano/genética , DNA Mitocondrial/genética , Humanos , Polimorfismo Genético , Análise de Sequência de DNARESUMO
We report a comprehensive statistical analysis of data on 58 DNA markers (mitochondrial [mt], Y-chromosomal, and autosomal) and sequence data of the mtHVS1 from a large number of ethnically diverse populations of India. Our results provide genomic evidence that (1) there is an underlying unity of female lineages in India, indicating that the initial number of female settlers may have been small; (2) the tribal and the caste populations are highly differentiated; (3) the Austro-Asiatic tribals are the earliest settlers in India, providing support to one anthropological hypothesis while refuting some others; (4) a major wave of humans entered India through the northeast; (5) the Tibeto-Burman tribals share considerable genetic commonalities with the Austro-Asiatic tribals, supporting the hypothesis that they may have shared a common habitat in southern China, but the two groups of tribals can be differentiated on the basis of Y-chromosomal haplotypes; (6) the Dravidian tribals were possibly widespread throughout India before the arrival of the Indo-European-speaking nomads, but retreated to southern India to avoid dominance; (7) formation of populations by fission that resulted in founder and drift effects have left their imprints on the genetic structures of contemporary populations; (8) the upper castes show closer genetic affinities with Central Asian populations, although those of southern India are more distant than those of northern India; (9) historical gene flow into India has contributed to a considerable obliteration of genetic histories of contemporary populations so that there is at present no clear congruence of genetic and geographical or sociocultural affinities.
Assuntos
Etnicidade/genética , Genética Populacional/métodos , Genômica , Cromossomos Humanos Y/classificação , Cromossomos Humanos Y/genética , DNA Mitocondrial/classificação , DNA Mitocondrial/genética , Emigração e Imigração/estatística & dados numéricos , Feminino , Efeito Fundador , Frequência do Gene/genética , Marcadores Genéticos/genética , Genômica/estatística & dados numéricos , Haplótipos/genética , Humanos , Índia , Idioma , FilogeniaRESUMO
Genetic affinities between the migrant groups of fishermen from Puri and their parental counterparts in the Southern areas were examined using 11 genetic loci: four blood groups, five red cell enzymes, and two serum proteins. The samples for the parental populations (about 430 subjects) were drawn from 34 villages spread along the 400 km coast in Ganjam district of Orissa and the contiguous Srikakulam, Vishakhapatnam, and East Godavari districts of Andhra Pradesh. Significant departures between the migrant groups and their parental counterparts were observed at some loci, although the configuration of interpopulation distances among the migrants mimicked that of the parental populations. While the observed differences may be due to a founder effect and subsequent random genetic drift in at least two of the three small populations, given high child mortality and the systematic nature of differences observed, the role of selection cannot be totally ruled out. © 1995 Wiley-Liss, Inc.
