HLA-B and HLA-C alleles and haplotypes in the Dravidian tribal populations of southern India

The Dravidians are believed to be the earliest inhabitants of India. Their subsequent migration and admixture with invading racial groups has been of scientific interest for population geneticists. In the present study, seven highly endogamous and extremely isolated colonies of Dravidian tribal populations (n = 105) from Kerala in South India were analysed and compared with random non-tribal Dravidian (RND) samples (n = 78) of southern India using the polymerase chain reaction with sequence-specific primer method for HLA-B and HLA-C typing. The tribal group comprises Adiya, Kanikkar, Kattunaikka, Kuruma, Kurichiya, Malapandaram and Paniya, while the RND group includes Malayalam-speaking individuals from various non-tribal castes of Kerala selected randomly. Some of the most frequent HLA-B alleles in the RND population were similar to the North Indian population and included B*07, B*61 (B*40), B*44, B*51, B*35 and B*52. Although B*61 was the most frequent allele in our total study population, the frequency fluctuated in individual populations. HLA-Cw*14 was one of the most frequent alleles while HLA-Cw*17 was totally absent in all populations studied. The haplotype B*61-Cw*14 was present in all the study groups except in Kurichiya, and the haplotype B*51-Cw*14 was only absent in Kattunaikka. Phylogenetic tree and correspondence analysis indicate that all the Dravidian tribal communities group together as a separate cluster, while the RND group of individuals from South India lie close to the North Indian population. This suggests that the RND population of South India might have a crypto-Dravidian origin, while the smaller Dravidian tribal communities have a distinct Dravidian origin.     

HLA polymorphisms in Sindhi community in Mumbai,India

Indian population is an amalgamation of various ethnicities, cultural and linguistic diversities, primarily due to marriages within a community. HLA-A, B and DRB1 alleles and haplotype frequencies were investigated in the Sindhi and compared with Marathi, Gujarati and North Indian population from Mumbai. This work is a part of a larger effort aimed at analysis of the HLA profile of diverse Indian ethnics to establish an umbilical cord stem cell panel in India. HLA polymorphisms at the HLA-A, B and DRB1 loci were determined in 413 cord blood samples by the molecular method of polymerase chain reaction using sequence-specific primer amplification. The most frequent alleles included A*01, A*02, A*11 and A*24 at A locus, B*35 and B*40 at B locus and DRB1*07 and DRB1*15 in all the four groups, although the frequency fluctuated in individual communities. HLA-DRB1*03 was significantly high (P < 0.05) in the Sindhi. Phylogenetic association using neighbour-joining tree, based on DA genetic distances for HLA-A and HLA-B alleles, indicated that the Sindhis cluster with North Indian and Pakistan Sindhi. The three locus haplotype analysis revealed that A*02-B*40-DRB1*15 and A*33-B*44-DRB1*07 were common haplotypes in all the groups. The three locus haplotypes found suggest an influence from Caucasian and Oriental populations. The data will be useful in developing an umbilical cord stem cell panel in India. The results will have clinical implications in unrelated umbilical cord stem cell for transplantation in India.     

HLA analysis of Sri Lankan Sinhalese predicts North Indian origin

The origin of the Sinhalese population of Sri Lanka is debated. We subtyped HLA-A*02 in 101 Sinhalese and observed a preponderance of the rare allele HLA-A*0211 which was similar to reported frequencies in northern India. Taken with low-resolution typing for the remaining A, B, C, DR and DQ alleles, these data suggest a North Indian origin for the Sri Lankan Sinhalese.     

HLA and B-lymphocyte alloantigens in Gila River Indians

HLA-A, B, C, DR, and MB and MT B-lymphocyte alloantigens were tested in 249 Pima and Papago Indians from Arizona. Frequencies of A and B locus antigens in Pimas were similar to published values for other North American Indians, as well as previous reports from Pimas. Cw3 was the most frequent C locus antigen found and DR5 was the most frequent DR antigen. Another B-cell specificity, DuB31, behaved as a DR allele and had a phenotype frequency of .717. This study is the first report of MB and MT frequencies in a North American Indian population, and the pattern of association with some DR antigens appears to be different from that observed in Europeans. MT3 had a phenotype frequency of .583, but was not associated with DR4, 7, 9, which suggests an undefined DR allele associated with MT3.     

Ultrasonographic Comparative Study of Biparietal Diameter in Fetuses of North Indian Women

This cross sectional study was conducted to evaluate accuracy of commonly used ultrasound dating formulae in specified North Indian population. BPD of fetuses of 841 singleton pregnant females was ultrasonographically measured for subsequent statistical analysis.The mean BPD for each GA (derived from LMP) of this study was statistically compared with mean BPD from that of published data by Hadlock et al., Shepard & Filly, Sabbagha & Hughey and Kurtz et al.. Square Regression Equation was selected to prepare a population specific BPD table for every respective GA.The results show that North Indian fetuses are smaller than European fetuses even before 3rd trimester and gestational ages derived from sonographic Western reference equations are underestimated in this population, hence IUGR is diagnosed frequently; suggesting the need of population specific charts.It is generally thought that the small size of Indian neonates at birth is attributable to small maternal size, an inadequate nutrient supply during late pregnancy, or both; but that early fetal growth, when nutrient requirements are very small and there are no constraints on space for growth, is similar to that of other populations.This suggests that any intervention designed to ensure appropriate fetal growth in North Indian populations would need to start pre-conceptionally or during early pregnancy.     

HLA-DR antigens in rheumatoid arthritis in North India

A study of 40 patients of classical or definite rheumatoid arthritis of North India origin diagnosed on ARA criteria revealed a significant increase in the frequency of HLA-DR4 (70%) as compared to the control population (1 2.5%) giving a relative risk of 16.33. Thus, in the native North Indian population, the genes for susceptibility to RA seem to be in linkage disequilibrium with the same DR determinant as in the white Caucasoid population.     

HLA-A and HLA-B distribution in Toto - a vanishing sub-Himalayan tribe of India

The frequency of HLA-A and HLA-B locus alleles was studied by using polymerase chain reaction-based sequence-specific primer method in a very primitive and vanishing sub-Himalayan Indian Tribe, the Toto population of North Bengal. The Toto, a Mongoloid tribe with a population size of 1172 reside only in the Totopara of Jalpaiguri district of North Bengal. We studied 40 individuals and observed some high frequency alleles when compared to other Indian tribal, non-tribal, and major world populations. Particularly, the frequency of HLA-B14 was 32.5% in the Toto population, the highest known frequency reported in any population in the world. This indigenous tribal population may harbour novel HLA alleles and unique haplotypes which extensive HLA genotyping will help to reveal, and thus further our understanding of their genetic admixture and migration patterns.     

Detection of two Blastomyces dermatitidis serotypes by exoantigen analysis

We evaluated the diagnostic value of antibody to Blastomyces dermatitidis A precipitin arcs for identifying B. dermatitidis cultures by the exoantigen technique with 88 isolates from the United States and Canada, 12 from Africa, and 1 each from India and Israel. In addition, we studied 190 mycelial-form isolates of other fungi which could be confused antigenically or morphologically with B. dermatitidis. Antigen extracts from all of the North American isolates, the Indian and Israeli isolates, and one of the African isolates reacted with the B. dermatitidis A antibody. The anti-A serum did not react with antigens from the other 11 African isolates or with antigens from any of the 190 heterologous fungi. Studies with unadsorbed and adsorbed antisera to selected North American and African isolates of B. dermatitidis showed that the North American isolates not only produced the distinct A antigen, but also formed another antigen that was common to all 11 of the antigenically less complex African isolates. The results of this study indicate that at least two serotypes of B. dermatitidis exist. All of the North American, Indian, and Israeli isolates and one of the African isolates contained the A antigen and were designated serotype 1. Most of the African isolates (11 of 12) constituted a second serotype that was deficient in A but showed an antigen designated K.     

Association of the wild-type A/A genotype of MBL2 codon 54 with asthma in a North Indian population

Background: High serumMBL level as well as polymorphisms in the mannose-binding lectin 2 (MBL2) gene resulting in MBL deficiency are involved in the mechanism of a number of non-infectious diseases such as asthma, conferring either risk or protection in different population studies. MBL being the first reactant of the MBL pathway is also a major determinant of the fate of the anaphylatoxins such as C3a and C5a, which are also pro-inflammatory mediators. The MBL2 gene polymorphisms thus control the serum levels of MBL as well as C3a and C5a. Objective: This is the first case-control study conducted in India, investigating the role of MBL2 codon 54 A/B polymorphism in asthma pathogenesis. Methods: A case-control study was performed with a total of 992 adult subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. The MBL2 codon 54 A/B polymorphism was genotyped by PCR-RFLP. Results: Statistical analysis for the codon 54 polymorphism revealed that the wild (A) allele was significantly associated with asthma with OR = 1.9, 95% CI (1.4–2.4), and p < 0.001. Conclusion: The MBL2 codon 54 A/B polymorphism is significantly associated with asthma and its phenotypic traits as the wild (A/A) genotype confers a significant risk towards the disease in the studied North Indian population.     

Population genetic study of the STR loci (HUMCSF1PO,HUMTPOX, HUMTHO1, HUMLPL,HUMF13A01, HUMF13B,HSFESFPS and HUMVWA) in North Indians

BACKGROUND: Highly polymorphic genetic markers like short tandem repeats (STRs) have been used successfully in disease analysis and studies of human evolution and population genetic diversity. However, DNA-based population genetic studies of Indian populations are limited. SUBJECTS AND METHODS: To enlarge our understanding of genetic variation in Indian populations, a population genetic study was carried out on Jat Sikh (Punjab, North India) individuals (n = 150) using a battery of the STR loci. The STR loci analysed by means of PCR amplification followed by electrophoresis and silver staining included HUMCSF1PO, HUMTPOX, HUMTHO1, HUMLPL, HUMF13A01, HUMF13B, HUMFESFPS and HUMVWA loci. RESULTS: The overall pattern of allele frequencies was similar to many Caucasian and Indian populations and heterozygosity varied from 65% (HUMLPL) to 85% (HUMVWA). For all eight loci, no deviations from the Hardy-Weinberg equilibrium hypothesis were detected. Significant differences were observed between Jat Sikhs and African, Chinese and Indian tribes. The mean exclusion probability ranged from 35% to 70%, and the power of discrimination from 81% to 93%, indicating the potential of these loci for forensic and paternity investigations. CONCLUSION: The allele frequency spectrum, heterozygosity, probability of exclusion, match probability and discrimination probability estimates show interesting variation and suggest the usefulness of these loci for anthropogenetic, paternity and forensic investigations in Indian populations.     

Population genetic study of the STR loci (HUMCSF1PO,HUMTPOX, HUMTHO1, HUMLPL,HUMF13A01, HUMF13B,HSFESFPS and HUMVWA) in North Indians

Background: Highly polymorphic genetic markers like short tandem repeats (STRs) have been used successfully in disease analysis and studies of human evolution and population genetic diversity. However, DNA-based population genetic studies of Indian populations are limited. Subjects and Methods: To enlarge our understanding of genetic variation in Indian populations, a population genetic study was carried out on Jat Sikh (Punjab, North India) individuals ( n = 150) using a battery of the STR loci. The STR loci analysed by means of PCR amplification followed by electrophoresis and silver staining included HUMCSF1PO, HUMTPOX, HUMTHO1, HUMLPL, HUMF13A01, HUMF13B, HUMFESFPS and HUMVWA loci. Results: The overall pattern of allele frequencies was similar to many Caucasian and Indian populations and heterozygosity varied from 65% (HUMLPL) to 85% (HUMVWA). For all eight loci, no deviations from the Hardy-Weinberg equilibrium hypothesis were detected. Significant differences were observed between Jat Sikhs and African, Chinese and Indian tribes. The mean exclusion probability ranged from 35% to 70%, and the power of discrimination from 81% to 93%, indicating the potential of these loci for forensic and paternity investigations. Conclusion: The allele frequency spectrum, heterozygosity, probability of exclusion, match probability and discrimination probability estimates show interesting variation and suggest the usefulness of these loci for anthropogenetic, paternity and forensic investigations in Indian populations.     

The hepatic veins: Anatomy and classification on single slice spiral CT in North Indian population

AimsTo find out the normal pattern of hepatic veins in the North Indian population and to categorize them.MethodsThe present study was conducted on 100 patients whose spiral CT abdomen was performed for various medical conditions in the department of radiodiagnosis.ResultsFour categories were recognized. Category-1, when right hepatic vein drains independently into the inferior vena cava whereas middle and left hepatic veins join together to form a common trunk before draining into the inferior vena cava. It was observed in 74% patients. Category-2 was observed in 2% patients, where right & middle hepatic veins join to form a common trunk and left hepatic vein drain independently into the inferior vena cava. Category-3 was observed in 21% patients, where all the three major hepatic veins drain independently into the inferior vena cava. Category-4 was observed in 3% patients, where all the three major hepatic veins join together to form a common trunk before draining into the inferior vena cava.ConclusionsCategory-1 is the most common pattern of major hepatic vein drainage found in the North Indian population. The present study also concluded that single right, middle and left hepatic vein is the most common pattern of hepatic veins present in the North Indian population. Caudate lobe is drained by more than one vein in majority of North Indians. Also superomedial vein, right accessory vein and inferior right hepatic vein are the most common accessory veins present in the North Indian population.     

Molecular diversity of the HLA-A*19 group of alleles in North Indians: possible oriental influence

The present study aims to determine the genetic diversity of the HLA-A19 allelic family in the North Indian and Japanese populations. The HLA-A*19 group of alleles occurred at similar frequencies in North Indians and Japanese as in Caucasians. All the known serological splits of HLA-A19 were observed among the North Indians, i.e. A*33 (15.6%), A*32 (8.6%), A*31 (3.5%), A*30 (3%), A*29 (1.2%) and A*74 (0.77%), while only A*30 (0.7%), A*31 (17.6%) and A*33 (11.7%) were observed in the Japanese. High resolution analysis indicated that the A*29, A*30, A*31 and A*32 alleles were represented by only single subtypes among the North Indians while the HLA-A*33 group comprised two alleles, A*3301 (4.3%) and A*3303 (43.7%). All 15 of the HLA-A*33 positive samples from the Tamil population of South India were found to be A*3303. One novel subtype of A*33, A*3306 was also observed in the North Indian sample. Conversely, only one subtype each of A*30, A*31 and A*33 was encountered in the Japanese population, of which A*3101 and A*3303 were the most frequent (58.5% and 39%, respectively, among the HLA-A*19 group of alleles). All other subtypes of A19 were not found in the Japanese in the present study. The study suggests a significant amount of genetic admixture in the North Indian gene pool from other racial groups, with profound oriental influence.     

Distribution of CCR2 polymorphism in HIV-1-infected and healthy subjects in North India

Substitution of V64I in CCR2 relates to delayed progression to AIDS and protects against HIV-1 infection. We examined the distribution of V64I in HIV-infected and healthy North Indian subjects. No significant difference in the allele or genotype distribution of CCR2 V64I polymorphism was observed, indicating that there is no association between CCR2 V64I polymorphism and susceptibility to HIV infection in North Indian population.     

Distribution of HLA antigens in the native South Indian Tamil Hindus

Blood samples from 240 unrelated healthy Tamil-speaking South Indian Hindus residing in Madras (capital city of Tamil Nadu, India) were screened for HLA-A and -B antigen profiles. Antigen, gene and haplotype frequencies were calculated and compared with the literature. Tamil Hindus lack A31, A32, Aw33, B16, B21 and Bw41. However, except for minor differences (low occurrence of Aw19 antigen), the South Indians show similarity to North Indian and other Indian groups. The data confirm once more that the haplotype A1-B17 is characteristic of Indians.     

HLA diversity among Nadars, a primitive Dravidian caste of South India

South India is one of the oldest geophysical regions mainly occupied by Dravidian language-speaking people. Here a random panel of 61 unrelated Nadar healthy individual from Tamil Nadu State were analyzed and compared with other populations of India and the world. HLA-A, B and C alleles frequencies and their haplotype frequencies were determined by high-resolution typing of genomic DNA. The analysis revealed that the Nadar caste of South India have several characters shared with East Asian populations consistent with the demographic history of South India, as well as specific features including several unique alleles such as A*03011, A*31011, B*15011, B*3501, B*51011, Cw*02022. In addition, haplotypes such as A*31011-Cw*02022-B*3501, A*03011-Cw*04011-B*4406 and A*2402101-Cw*04011-B*51011 are of high frequency in both these populations but are rare or absent in other populations of India and the world. The study suggests that a comparatively lesser degree of genetic admixture occurred between the South Indian and North Indian racial groups than that between South Indian and East Asian groups.     

Determination of Sex from Mastoid Process By Discriminant Function Analysis

Sex determination is vital for the identification of an individual. Often fragmentary remains are available for forensic identification making sex determination difficult. The mastoid region, a fragmentary piece of skull, is ideal for studying sexual dimorphism as it is resistant to damage due to its anatomical position at the base of skull. The skull measurements vary significantly in different ethnic groups and the discrimination models for Indian populations are rare.In the present study, 60 adult human skulls of North Indian individuals were studied to determine accuracy of mastoid process in sex determination. Mastoid length, breadth and antero-posterior diameter of the mastoid process were measured to calculate the size of mastoid process.Discriminant function analysis revealed that mastoid process correctly classified the sex in 76.7% of the subjects and mastoid length was found to be the best determinant for sex although the classification rate dropped to 66.7%. A discriminant function equation specific for North Indian population has also been derived from mastoid variables.     

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 today's 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.     

North and South Indian Populations Share a Common Ancestral Origin of Friedreich's Ataxia but Vary in Age of GAA Repeat Expansion

Friedreich's ataxia (FRDA) is caused by expansion of GAA repeats in the frataxin (FXN) gene on chromosome 9q13‐q21.1. We analysed the origin of FRDA in 21 North Indian (NI) and eight South Indian (SI) families using five single nucleotide polymorphisms (SNPs) and a microsatellite marker spanning the GAA repeats. The NI and SI families were derived from Indo‐European and Dravidian linguistic backgrounds respectively. The frequency of large normal (LNs) alleles of the GAA repeat correlate with the overall lower prevalence of FRDA in India compared to the European population. All of the expanded alleles in the Indian population share a common core haplotype suggesting a founder effect. The expanded alleles in the NI population demonstrate more similarity to those of Europeans in terms of age of GAA repeat expansion (15975 ± 2850 years) and association of LNs with expanded alleles. FRDA seems to have been introduced recently in the South Indian population since the average estimated age of the mutation in SI is 5425 ± 1750 years and unlike NI some of the haplotypes of LNs are not associated with the expanded alleles.     

The HLA system in the prevalent Mexican Indian group: the Nahuas

Results of HLA-A, B and C typing as well as haplotype frequencies in the Nahuas, who are the predominant Indian group in Mexico are presented. ABO and Rh blood groups show the genetic homogeneity of this population, since all of them were group O and Rh⁺. The most frequent antigens and haplotype are in general, the same as in some, but not all Amerindian tribes (Papago, Pimas, Zuñi from North America and Ixils from Guatemala). When-compared to other Mongoloids, the HLA pattern is very close to the Japanese population. Antigens Bw39 and Cw4 look like markers of Nahuas and because Bw16 cells from four individuals could not be assigned either as Bw38 or Bw39, and 6 subjects did not type for any of the Bw22 splits, new subtypes of these antigens are probable.