Faisal Khan

Phylogeny of Mitochondrial DNA Macrohaplogroup N in India, Based on Complete Sequencing: Implications for the Peopling of South Asia

To resolve the phylogeny of the autochthonous mitochondrial DNA (mtDNA) haplogroups of India and determine the relationship between the Indian and western Eurasian mtDNA pools more precisely, a diverse subset of 75 macrohaplogroup N lineages was chosen for complete sequencing from a collection of >800 control-region sequences sampled across India. We identified five new autochthonous haplogroups (R7, R8, R30, R31, and N5) and fully characterized the autochthonous haplogroups (R5, R6, N1d, U2a, U2b, and U2c) that were previously described only by first hypervariable segment (HVS-I) sequencing and coding-region restriction-fragment-length polymorphism analysis. Our findings demonstrate that the Indian mtDNA pool, even when restricted to macrohaplogroup N, harbors at least as many deepest-branching lineages as the western Eurasian mtDNA pool. Moreover, the distribution of the earliest branches within haplogroups M, N, and R across Eurasia and Oceania provides additional evidence for a three-founder-mtDNA scenario and a single migration route out of Africa.

Relationship between GSTs Gene Polymorphism and Susceptibility to End Stage Renal Disease among North Indians

Background and Objective. Glutathione-S-transferase (GST) is the superfamily of genes that provides protection to the cells against reactive oxygen species and plays a vital role in phase II of biotransformation of many substances. Overexpression of GST (EC 2.5.1.18) has been documented in the erythrocytes of patients with chronic renal failure, which may be of clinical relevance. Keeping this background in mind, we have investigated the relationship between human GST gene polymorphism in end stage renal disease (ESRD) patients. Design and Methods. We have assessed 184 patients with ESRD and 569 age-and sex-matched controls from North India. The GSTT1 and GSTM1 null genotypes were identified by polymerase chain reaction (PCR). GSTP1–313 A/G mutation was determined by PCR followed by restriction enzyme digestion. Results. The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphism were evaluated. We observed that GSTM1 null genotype was present in 46.74% of the ESRD patients while GSTT1 null genotype was present in 58.7% of the ESRD subjects. The genotypic distribution of GSTP1 was Ile105/Ile105 in 47.3%, Ile105/Val105 in 30.97% and Val105/Val105 in 21.74% of ESRD patients. There was a significant association of null alleles of the GSTM1 (p = 0.0386; OR = 1.445, 95% CI = 1.033–2.021) and GSTT1 (p ≤ 0.0001; OR = 4.568, 95% CI = 3.215–6.492) and in the -313 G alleles (Val) of the GSTP1 gene (p = 0.0032; OR = 1.956, 95% CI = 1.265–3.024) with end stage renal disease. The combined analysis of the three genotypes showed a further increased risk to ESRD (p ≤ 0.0001; OR = 9.01, 95% CI = 5.55–14.626). Interpretations and Conclusions. The null / low polymorphism of the detoxifying enzymes GSTT1, GSTM1, and GSTP1 are associated with the risk of developing ESRD in North Indian patients.

Presence of three different paternal lineages among North Indians: a study of 560 Y chromosomes.

Background: The genetic structure, affinities, and diversity of the 1 billion Indians hold important keys to numerous unanswered questions regarding the evolution of human populations and the forces shaping contemporary patterns of genetic variation. Although there have been several recent studies of South Indian caste groups, North Indian caste groups, and South Indian Muslims using Y-chromosomal markers, overall, the Indian population has still not been well studied compared to other geographical populations. In particular, no genetic study has been conducted on Shias and Sunnis from North India. Aim: This study aims to investigate genetic variation and the gene pool in North Indians. Subjects and methods: A total of 32 Y-chromosomal markers in 560 North Indian males collected from three higher caste groups (Brahmins, Chaturvedis and Bhargavas) and two Muslims groups (Shia and Sunni) were genotyped. Results: Three distinct lineages were revealed based upon 13 haplogroups. The first was a Central Asian lineage harbouring haplogroups R1 and R2. The second lineage was of Middle-Eastern origin represented by haplogroups J2*, Shia-specific E1b1b1, and to some extent G* and L*. The third was the indigenous Indian Y-lineage represented by haplogroups H1*, F*, C* and O*. Haplogroup E1b1b1 was observed in Shias only. Conclusion: The results revealed that a substantial part of todays North Indian paternal gene pool was contributed by Central Asian lineages who are Indo-European speakers, suggesting that extant Indian caste groups are primarily the descendants of Indo-European migrants. The presence of haplogroup E in Shias, first reported in this study, suggests a genetic distinction between the two Indo Muslim sects. The findings of the present study provide insights into prehistoric and early historic patterns of migration into India and the evolution of Indian populations in recent history.

Microsatellite Variation at 24 STR Loci in Three Endogamous Groups of Uttar Pradesh, India

We have studied variation at 24 microsatellite markers among 50 individuals from each of three endogamous groups, Bhargavas, Chaturvedis, and non-Bhargava, non-Chaturvedi Brahmins of Uttar Pradesh, India. The number of alleles at the loci tested varied from 4 to 11, with an average of 6 at each locus. Heterozygosity was found to be quite high at all loci in the three subpopulations. It varied between 0.44 to 0.84 among Bhargavas (average 0.6510), 0.44 to 0.80 among Chaturvedis(average 0.6633±), and 0.42 to 0.85 among Brahmins (average 6.694±). Hardy-Weinberg equilibrium analysis revealed that these populations are under genetic equilibrium at almost all the loci tested. Comparisons of allele frequency between Bhargavasand Chaturvedis showed that they differed significantly at 14 short tandem repeat (STR) markers (p < 0.001), while Chaturvedis and Brahmins differed at 6 (p < 0.05) and Brahmins and Bhargavas at 8 (p < 0.05). Average FIS and FST for the 24 STR markers was -0.02 and 0.013, respectively. We used both unweighted pair group with arithmetic mean and principal components analysis to evaluate genetic distances among the three groups. Our results revealed that although there were differences at particular allele frequencies between Bhargavas vs. Brahmins, Bhargavas vs. Chaturvedis, and Brahmins vs. Chaturvedis, these differences were not statistically significant when combined over all 24 STR markers between Chaturvedis vs. Brahmins and Bhargavas vs. Brahmins. The genetic distance analysis revealed that Bhargavas are slightly apart from the other two populations.

Evaluation of six short tandem repeat Loci in forensics: North Indian populations

The allele frequency estimates of these STR markers reveal that alleles are not equally distributed in all the three populations included in the study.

Distribution of allele frequencies of six STR markers in north Indians.

Extraction: Modified salting out technique (1) followed by phenol—chloroform extraction and ethanol precipitation.

Allele Frequencies of Microsatellite Repeat Loci in Bhargavas, Chaturvedis, and Brahmins of North India

Extraction: Modified salting out technique (1) followed by phenol—chloroform extraction and ethanol precipitation.

DNA short tandem repeat profiling of three North Indian populations.

POPULATION Fifty healthy unrelated individuals were randomly chosen from each of the three populations viz., Bhargavas, Chaturvedies, and Brahmins. Three generation pedigree charts were prepared to ensure sirname endogamy in Bhargavas Chaturvedies and group endogamy in Brahmins subjects were chosen from several parts of Uttar Pradesh, a northern state of the Indian republic.

ApoB 3’HVR Polymorphism a Genetic Variation in Indian Subcontinent

Abstract Apo B 3’ hyper variable region (Apo B 3’ HVR) is a highly polymorphic and hence an informative marker. It could be an ideal candidate to study the genetic heterogeneity among different population groups of Indian subcontinent. It is one of the marker for which numerous population data is available. This makes Apo B 3’HVR an ideal locus for a pilot study to investigate the relationships between different populations and the micro-evolutionary processes leading to their present day distribution. In the present study, we have studied ApoB3’HVR among North Indians and South Indians and have compared these populations on the basis of within group and between group diversity. For this purpose we have selected 600 North Indians and 200 South Indians at random. Total 21 segregating alleles were detected in our population groups. The average observed heterozygosity was quite high (avg.0.753) suggesting high diversity at ApoB’3HVR locus. Low value of average Gst (0.0005) and Fst (0.035) reflects non-significant deviation of heterozygosity between the two groups. On comparing our study populations with central Indian non tribal and tribal groups, it was found that there is relative homogeneity among the three non tribal groups and on computing genetic distances between the four groups, it was observed that tribal significantly differ from the three non-tribal groups. On comparing with other world populations grouped in continental groups, it was clear that greater diversity was observed for Africans followed by the Europeans and Asians. There was relative homogeneity among the continental groups. North Indians and South Indians were found closure to the Asians while non tribal Central Indians clustered with the Eurpeans. We are further testing these observations, by incorporating more realistic demographic models and by using mt-DNA for maternal lineages and Y-chromosome markers for paternal lineages.