Benrithung Murry

Spectrum of MTHFR gene SNPs C677T and A1298C: a study among 23 population groups of India.

Elevated homocysteine is a risk factor for many complex disorders. The role of methylenetetrahydrofolate reductase (MTHFR) gene in methylation of homocysteine makes it one of the most important candidate genes for these disorders. Considering the heterogeneity in its distribution in world populations, we screened MTHFR C677T and A1298C single nucleotide polymorphisms in a total of 23 Indian caste, tribal and religious population groups from five geographical regions of India and belonging to four major linguistic groups. The frequencies of MTHFR 677T and 1298C alleles were found to be 10.08 and 20.66%, respectively. MTHFR homozygous genotype 677TT was absent in eight population groups and homozygous 1298CC was absent in two population groups. 677T allele was found to be highest among north Indian populations with Indo-European tongue and 1298C was high among Dravidian-speaking tribes of east India and south India. The less common mutant haplotype 677T-1298C was observed among seven population groups and overall the frequency of this haplotype was 0.008, which is similar to that of African populations. cis configuration of 677T and 1298C was 0.94%. However, we could not find any individual with four mutant alleles which supports the earlier observation that presence of more than two mutant alleles may decrease the viability of foetus and possibly be a selective disadvantage in the population.

A Genomic Insight into Diversity Among Tribal and Nontribal Population Groups of Manipur, India

Twenty autosomal markers, including linked markers at two gene markers, are used to understand the genomic similarity and diversity among three tribal (Paite, Thadou, and Kom) and one nontribal communities of Manipur (Northeast India). Two of the markers (CD4 and HB9) are monomorphic in Paite and one (the CD4 marker) in Kom. Data suggest the Meitei (nontribal groups) stand apart from the three tribal groups with respect to higher heterozygosity (0.366) and presence of the highest ancestor haplotypes of DRD2 markers (0.228); this is also supported by principal co-ordinate analysis. These populations are found to be genomically closer to the Chinese population than to other Indian populations.

Prevalence of β-Thalassemia and Hemoglobin E in Two Migrant Populations of Manipur, North East India

Hemoglobinopathies are a group of inherited single-gene disorders found commonly in the Mediterranean region, Middle East, Indian subcontinent, Burma, and South East Asia. As many as 229 mutation variants of β-thalassemia are reported in the world, many community/region-specific mutations. Very little on thalassemia has been reported in Manipur, a North Eastern Indian state. Thus, a community genetic approach through population screening can be applied to the people of Manipur and a total of 602 blood samples from unrelated Meitei Brahmins (n=300) and Meitei Muslims (n=302) were screened for abnormal hemoglobins by Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT). HBA(2) level was estimated by using high-performance liquid chromatography and molecular analysis was done by using PCR. Sequencing was also carried out to confirm the mutations. High frequencies of NESTROFT positive (10%) and NESTROFT doubtful (11%) cases were found among the Meitei Brahmins in comparison to the Meitei Muslims [NESTROFT positive (3.31%) and NESTROFT doubtful (1.33%)]. The allele frequency of HB*E was 0.022 and 0.012 among the Meitei Brahmin and Meitei Muslim, respectively. Sequencing of the β-globin gene confirmed a very rare β-thalassemia [-90 C→T (0.33%)] among the Meitei Brahmins of Manipur. This mutation with hemoglobin E in one of the present population hints the presence of the Mongoloid stock among them, possibly from China. There is a need for further studies on other populations of Manipur and the neighboring North East Indian states using such genetic markers.

Population Severance in Manipur at Dopamine Receptor D2 Locus

INTRODUCTION Tibeto-Burman language-speaking Mongoloid groups of northeast India are reported to be genetically highly heterogeneous. Manipur, one of the states of this region sharing a major International border with Myanmar, is also expected to be diversified as seen by its large number of tribal and nontribal groups. A number of genomic markers, that is, autosomal, mitochondrial, and Y chromosomal ones, have been used to understand the peopling of the northeast region. AIMS In this article, an attempt is made to understand the peopling of Manipur using three sites (Taq1A, Taq1B, and Taq1D) on the dopamine receptor D2 (DRD2) gene through allele and haplotype frequencies and their distribution patterns. METHODS In total, 367 blood samples were collected from eight populations of which three (Meitei, Muslims, and Bamon) are nontribal groups and five (Aimol, Kabui, Paite, Kom, and Thadou) are tribal groups. RESULTS All the three sites are polymorphic in all the studied populations with relatively lower heterozyosities indicating a genetic discontinuity between the populations of mainland India and northeast India, suggesting the unlikeliness of eastward migration of people from Africa through India. CONCLUSION High heterogeneity and predominance of ancestral haplotype (B2D2A1) among the Meitei suggest an admixture of incoming mongoloid groups with an already existing protoastroloid element. The study also highlights the distinctiveness of Manipuri population groups with respect to DRD2 gene polymorphism.

Brief communication: Allelic and haplotypic structure at the DRD2 locus among five North Indian caste populations

The dopamine D2 receptor (DRD2) gene, with its known human-specific derived alleles that can facilitate haplotype reconstruction, presents an important locus for anthropological studies. The three sites (TaqIA, TaqIB, and TaqID) of the DRD2 gene are widely studied in various world populations. However, no work has been previously published on DRD2 gene polymorphisms among North Indian populations. Thus, the present study attempts to understand the genetic structure of North Indian upper caste populations using the allele and haplotype frequencies and distribution patterns of the three TaqI sites of the DRD2 gene. Two hundred forty-six blood samples were collected from five upper caste populations of Himachal Pradesh (Brahmin, Rajput and Jat) and Delhi (Aggarwal and Sindhi), and analysis was performed using standard protocols. All three sites were found to be polymorphic in all five of the studied populations. Uniform allele frequency distribution patterns, low heterozygosity values, the sharing of five common haplotypes, and the absence of two of the eight possible haplotypes observed in this study suggest a genetic proximity among the selected populations. The results also indicate a major genetic contribution from Eurasia to North Indian upper castes, apart from the common genetic unity of Indian populations. The study also demonstrates a greater genetic inflow among North Indian caste populations than is observed among South Indian caste and tribal populations.

Estimates of fertility and mortality differentials among the Lotha Nagas of Nagaland.

Abstract Data were collected from 546 ever married Lothas, a scheduled tribe population of Wokha district of Nagaland, with a view to understand their reproductive performance and the factors affecting fertility. The CBR, GFR, TFR and GRR of the Lothas are found to be 28.35, 192.05, 7.15 and 3.88, respectively. Variables such as education, use of BCM and age at menarche are not found to have contributed significantly to fertility. Socio-cultural factors seem to have played an important role in determining fertility. Of all deaths prenatal mortality was highest (56.62%) of what about 60% are found to be cases of induced abortion. The least fertile age groups of the Lothas are found to be at greater genetic risks to the prenates. It is also found that mortality decreased with proper vaccination and better income level.

Isonymy and repeated pairs of surnames among the Muslims of Manipur, India.

Surnames have been used for studying population structure in different parts of the globe. The present study is aimed at indirectly estimating the degree of inbreeding from surnames and understanding the influences of the clan-like structure on mate selection among Manipuri Muslims. The proportion of isonymy I was found to be 0.0144. The non-random and random components were -0.0226 and 0.0239, respectively. The total inbreeding coefficient was estimated to be 0.0018. The scores of random pairs (RP) and random repeated pairs (RPr) were 0.026 and 0.010, respectively. The score of RP was higher than the RPr which gives a ratio of 0.38, indicating that Manipuri Muslims have a tendency of acquiring mates from within a given set of surnames while not in favour of isonymy. To conclude, surname/clan is a criterion for mate selection for various reasons among this population.

APOE, MTHFR, LDLR and ACE Polymorphisms Among Angami and Lotha Naga Populations of Nagaland, India

Several common polymorphisms in the ApoE, ACE, MTHFR and LDLR genes have been implicated in the pathogenesis of common complex diseases across world populations. This study investigates the prevalence of five known and clinically important common polymorphisms in Angami and Lotha Naga populations. A total of 112 unrelated healthy volunteers (52 Lotha Nagas and 60 Angami Nagas) participated in the study. All the five genes were found to be polymorphic in the studied populations. The Lotha Nagas displayed higher mutant allele frequencies than the Angami Nagas except for the T allele frequency of the AvaII polymorphism of the LDLR gene, though chi square did not reveal any significant population differences by genotypes. In view of the relatively high mutant allele frequencies in both the populations, they are likely to be at a high risk of developing various complex diseases as they shift from an active and rigorous lifestyle to a more sedentary one.

Incidence of NESTROFT - Positives and Haemoglobin S Among the Lotha Nagas of Nagaland

Abstract Naked eye single tube osmotic fragility test (NESTROFT) was performed on the blood samples of 315 randomly selected Lotha individuals. 280 individuals were also tested for the presence of sickle cell haemoglobin. 12.70 percent NESTROFT-positive and 3.81 percent doubtful cases were detected. Not a single case of HbS was found.

Prevalence of MTHFR, Factor V, ACE and APOE gene polymorphisms among Muslims of Manipur, India

Background: Chronic metabolic disorders such as cardiovascular disease and diabetes have become an emerging public health problem in India, in both rural and urban settings. Genetic markers like MTHFR, FV, ACE and APOE are important candidates involved in the development of these disorders. Aim: The present study aims to understand the distribution of allele frequencies of the SNPs in the above-mentioned genes in Manipuri Muslims, an endogamous religious community constituting∼8% of the Manipur population. Sample and methods: Blood samples were collected from 107 unrelated healthy individuals. Genotyping were done by PCR (for ACE I/D and MTHFR A1298C) followed by restriction digestion (for MTHFR C677T, FV G1691A and APOE). Results and discussion: All four SNPs, with the exception of FVL, were found to be polymorphic, with allele frequencies of 15.1%, 17%, 36.1% and 7.7% for MTHFR 677T, MTHFR 1298C, ACE D and APOE E4, respectively. The D allele of ACE I/D polymorphism was found to be significantly higher among males and also among the young age group compared with females and the old age groups, respectively. This study has highlighted the necessity of looking at the clinical implications of these SNPs in future studies of Manipuri Muslims.