A.K. Kalla

Evidence of a common founder for SCA12 in the Indian population.

Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5′ region of the PPP2R2B gene on chromosome 5q31–5q32. We found that it accounts for ∼16% (20/124) of all the autosomal dominant ataxia cases diagnosed in AIIMS, a major tertiary referral centre in North India. The length of the expanded allele in this population ranges from 51–69 CAG triplets. Interestingly, all the affected families belong to an endogamous population, which originated in the state of Haryana, India. We identified four novel SNPs and a dinucleotide marker spanning ∼137 kb downstream of CAG repeat in the PPP2R2B gene. Analysis of 20 Indian SCA12 families and ethnically matched normal unrelated individuals revealed one haplotype to be significantly associated with the affected alleles (P= 0.000), clearly indicating the presence of a common founder for SCA12 in the Indian population. This haplotype was not shared by the American pedigree with SCA12. Therefore, the SCA12 expansion appears to have originated at least twice.

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.

Folate supplementation, MTHFR gene polymorphism and neural tube defects: a community based case control study in North India

The present study analyses the potential role of MTHFR gene polymorphism, folate supplementation and dietary pattern among the mothers of NTD neonates and controls in heterogeneous populations of North India, with the special focus on their ethnic labels. Results indicated significant increased risk for neural tube defects with respect to low folic acid supplementation and vegetarian diet in univariate and multivariate analyses. There was no significant difference in the genotypic or allelic distribution of MTHFR C677T polymorphism, however, high frequency of CT genotype, as observed, among controls suggests heterozygous advantage probably due to supplementary folate. Among the two communities, Muslim NTD mothers had higher TT genotype showing increased risk for neural tube defects (adjusted OR: 12.9; 95% CI: 1.21–136.8) and lower folic acid supplementation (adjusted OR: 3.5; 95% CI: 1.18–10.22). Whereas, marginal increased risk for NTDs with vegetarian diet was observed among Hindus. Cultural and ethnic variation in the risk factors for neural tube defects is highlighted in the study.

Diversified genomic contribution among south Indian populations–A study on four endogamous groups of Andhra Pradesh

Background: The present study examines genomic variation among three tribal (Nayakpod, Thoti and Kolam) and a caste (Niyogi Brahmin) population groups of Andhra Pradesh, south India. Aim: The present study examined the genomic diversity of the populations in relation to other population groups of India using 20 autosomal loci. Subjects and methods: A total of 204 blood samples from the population groups described above were collected and analysis was carried out following standard protocols. Results: All markers were found to be polymorphic in these groups except AluCD4 among Thotis. High average heterozygosity values (0.3927 among Thotis to 0.4268 among Brahmins) are comparable with the available autosomal (Alu and restriction site polymorphisms) data for the Nilgiri hill tribes of Tamil Nadu, south India. The gene differentiation value (Gst) was found to be 4.2. The principal coordinate analysis (PCO) based on data from the 20 markers presents a smaller cluster of presently studied populations than that of the Nilgiri hill tribes of Tamil Nadu, south India. Conclusion: Although the presently studied populations of Andhra Pradesh have heterozygosity similar to that of Nilgiri hill populations, the former are more closely placed on the PCO plot than the latter, who are more scattered. Also the gene differentiation (Gst) of the former is much lower than that of the latter, indicating considerable regional variation in the inflow of genes from diverse ethnic groups within south India.

Pro-inflammatory cytokine gene polymorphisms and threat for coronary heart disease in a North Indian Agrawal population

The association of IFN-γ (+874 A/T; rs2430561), TNF-α (-308 G/A; rs1800629) and TNF-β (+252 A/G; rs909253) with Coronary Heart Disease (CHD) has not been rigorously tested in Indian population. In the present study we sought to examine the role of these cytokines in the causation of CHD and their association with conventional CHD risk factors. A total of 138 case and 187 unrelated healthy controls aged 35 to 80years, matched on ethnicity and geography were collected from North Indian Agrawal population. Single nucleotide polymorphisms at the promoter TNF-α -308 G/A and the intronic IFN-γ +874 A/T were analyzed by allele-specific PCR, and the intronic TNF-β +252 A/G was analyzed by RFLP. Of the three selected polymorphisms, genotypic distribution of IFN-γ +874 A/T and TNF-β +252 A/G polymorphisms was significantly different between patients and controls in the present study. OR revealed statistically significant risk for CHD with respect to IFN-γ +874 T allele, whereas OR for TNF-β +252 A/G showed three fold risk in homozygous condition though not significant. No such trend could be observed for TNF-α -308 G/A polymorphism. Multivariate logistic regression after adjusting for all the confounders showed significant risk for CHD with the genotypes and genotypic combinations of all the three markers (albeit not significant with TNF-α). Increased risk for CHD was likely to be associated with interaction of IFN-γ with diastolic hypertension, TNF-α with diabetes and BMI, and TNF-β with serum triglyceride and very low density lipoprotein (VLDL) levels. The results suggest that these selected cytokine polymorphisms could possibly serve as potential bio-markers for CHD in conjunction with specific conventional risk factors.

Kinship System, Fertility and Son Preference among the Muslims: A Review

Abstract This review illustrates that differences in kinship system between north (by an large patrilineal) and south (by an large matrilineal) of India is an important factor to bring about regional disparities in sex preference of children by the Hindu parents but not by the Muslim parents in whom Kinship system is traditionally unique as it shares similarity with Dravidian system in marriage pattern and inheritance from paternal side and similarity in kinship terminology with Indo Aryan system of the north while among the Hindus it is traditionally based on patrilineal inheritance, not withstanding the Hindu succession Act of 1956’. Though dowry and sex selective abortion are the determinants of status of women among the Hindus, they are generally not practiced among the Muslims. However, the lower education status, economic status and social status (due to patriarchy and religious ideologies) respectively and together produce circumstances leading to son being seen as the best socio-economic insurance by the Muslim women. This review of studies conducted on the above topic shows that high fertility among the Muslim women is also a consequence of son preference arising out of socio-economic compulsion in the traditional absence (due to strict religious prohibition) of sex selective abortions.

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.

Short ReportGenetic variation at three VNTR loci (D1S80, APOB and D17S5) in two tribal populations of Andhra Pradesh, India

This study reports the genetic variation at three variable number of tandem repeat (VNTR) loci (APOB, D17S5 and D1S80) in two tribes (Thoti and Kolam) of Andhra Pradesh, India. Kolams constitute 1% of the total scheduled tribal population of Andhra Pradesh, while Thoti is a numerically small tribe. All three genetic loci were genotyped using the polymerase chain reaction (PCR) technique and were polymorphic in both populations. At the D1S80 locus, both populations showed higher frequencies of allele *31 (9–14%) than other Indian populations. In the APOB system, Thoti showed a very high frequency of allele *37 (54%) and for D17S5 system allele *4 was the most common in Thoti (32%) and allele *2 in Kolam (28%). Both tribes differed statistically significantly from other tribal populations of the region. The level of gene differentiation was low (GST = 0.038) for Indian tribal populations. The allele frequency distribution, heterozygosity and genetic diversity analysis shows that the observed genetic variation is socially and geographically structured.

Demographic Profile of Thoti - A Primitive Tribal Population of Andhra Pradesh

Abstract The Thoti is a primitive tribal population fou nd in Adilabad district of Andhra Pradesh practicing a high degree of consangu ineous marriages. In the present paper an attempt has been made to give a dem ographic profile of the Thoti pertaining to age at menarche, age at marriage, age at first live birth, menopa use and outcome of pregnancy. For this, data were collected from a total of 246 ever married Thoti women. Furthermore, average fertility and average offspring mortality per women and the percentage of different types of offspring mortality alongwith different rates for fertility and offspring mortality as well as coefficient of inbreedingwere calculated.

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.