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S S Papiha

Publications and source records attributed to S S Papiha.

At least 19 recordsLinked to original sources
PubMed2003

The genetic heritage of the earliest settlers persists both in Indian tribal and caste populations.

Two tribal groups from southern India--the Chenchus and Koyas--were analyzed for variation in mitochondrial DNA (mtDNA), the Y chromosome, and one autosomal locus and were compared with six caste groups from different parts of India, as well as with western and central Asians. In mtDNA phylogenetic analyses, the Chenchus and Koyas coalesce at Indian-specific branches of haplogroups M and N that cover populations of different social rank from all over the subcontinent. Coalescence times suggest early late Pleistocene settlement of southern Asia and suggest that there has not been total replacement of these settlers by later migrations. H, L, and R2 are the major Indian Y-chromosomal haplogroups that occur both in castes and in tribal populations and are rarely found outside the subcontinent. Haplogroup R1a, previously associated with the putative Indo-Aryan invasion, was found at its highest frequency in Punjab but also at a relatively high frequency (26%) in the Chenchu tribe. This finding, together with the higher R1a-associated short tandem repeat diversity in India and Iran compared with Europe and central Asia, suggests that southern and western Asia might be the source of this haplogroup. Haplotype frequencies of the MX1 locus of chromosome 21 distinguish Koyas and Chenchus, along with Indian caste groups, from European and eastern Asian populations. Taken together, these results show that Indian tribal and caste populations derive largely from the same genetic heritage of Pleistocene southern and western Asians and have received limited gene flow from external regions since the Holocene. The phylogeography of the primal mtDNA and Y-chromosome founders suggests that these southern Asian Pleistocene coastal settlers from Africa would have provided the inocula for the subsequent differentiation of the distinctive eastern and western Eurasian gene pools.

Asia, Central↗
PubMed2001

Genetic evidence on the origins of Indian caste populations.

The origins and affinities of the approximately 1 billion people living on the subcontinent of India have long been contested. This is owing, in part, to the many different waves of immigrants that have influenced the genetic structure of India. In the most recent of these waves, Indo-European-speaking people from West Eurasia entered India from the Northwest and diffused throughout the subcontinent. They purportedly admixed with or displaced indigenous Dravidic-speaking populations. Subsequently they may have established the Hindu caste system and placed themselves primarily in castes of higher rank. To explore the impact of West Eurasians on contemporary Indian caste populations, we compared mtDNA (400 bp of hypervariable region 1 and 14 restriction site polymorphisms) and Y-chromosome (20 biallelic polymorphisms and 5 short tandem repeats) variation in approximately 265 males from eight castes of different rank to approximately 750 Africans, Asians, Europeans, and other Indians. For maternally inherited mtDNA, each caste is most similar to Asians. However, 20%-30% of Indian mtDNA haplotypes belong to West Eurasian haplogroups, and the frequency of these haplotypes is proportional to caste rank, the highest frequency of West Eurasian haplotypes being found in the upper castes. In contrast, for paternally inherited Y-chromosome variation each caste is more similar to Europeans than to Asians. Moreover, the affinity to Europeans is proportionate to caste rank, the upper castes being most similar to Europeans, particularly East Europeans. These findings are consistent with greater West Eurasian male admixture with castes of higher rank. Nevertheless, the mitochondrial genome and the Y chromosome each represents only a single haploid locus and is more susceptible to large stochastic variation, bottlenecks, and selective sweeps. Thus, to increase the power of our analysis, we assayed 40 independent, biparentally inherited autosomal loci (1 LINE-1 and 39 Alu elements) in all of the caste and continental populations (approximately 600 individuals). Analysis of these data demonstrated that the upper castes have a higher affinity to Europeans than to Asians, and the upper castes are significantly more similar to Europeans than are the lower castes. Collectively, all five datasets show a trend toward upper castes being more similar to Europeans, whereas lower castes are more similar to Asians. We conclude that Indian castes are most likely to be of proto-Asian origin with West Eurasian admixture resulting in rank-related and sex-specific differences in the genetic affinities of castes to Asians and Europeans.

Adult↗
PubMed2000

The human peroxisome proliferator-activated receptor alpha gene: identification and functional characterization of two natural allelic variants.

Peroxisome proliferator-activated receptor (PPAR)alpha-null mice have a defect in fatty acid metabolism but reproduce normally. The lack of a detrimental effect of the null phenotype in development and reproduction opens up the possibility for null or variant PPARalpha gene (PPARA) alleles in humans. To search the coding region and splice junctions for mutant and variant PPARalpha alleles, the human PPARalpha gene was cloned and characterized, and sequencing by polymerase chain reaction was carried out. Two point mutations in the human gene were found in the DNA binding domain at codons for amino acids 131 and 162. The allele containing the mutation in codon 162 (CTT to GTT, L162V) designated PPARA*3, was found at a high frequency in a Northern Indian population. Transfection assays of this mutant showed that the non-ligand dependent transactivation activity was less than one-half as active as the wild-type receptor. PPARA*3 was also unresponsive to low concentrations of ligand as compared to the wild-type PPARA*1 receptor. However, the difference is ligand concentration-dependent; at concentrations of the peroxisome proliferator Wy-14 643 > 25 microM, induction activity was restored in this variant's transactivation activity to a level five-fold greater as compared with wild-type PPARA*1 with no ligand. The mutation in codon 131 (CGA to CAA, R131Q), designated PPARA*2 is less frequent than PPARA*3, and the constitutive ligand independent activity was slightly higher than PPARA*1. Increasing concentrations of Wy-14 643 activated PPARA*2 similar to that observed with PPARA*1. The biological significance of these novel PPARalpha alleles remains to be established. It will be of great interest to determine whether these alleles are associated with differential response to fibrate therapy.

Alleles↗
PubMed2000

Distribution of the 3' VNTR polymorphism in the human dopamine transporter gene in world populations.

A polymorphism with a variable number of tandem repeats (VNTR) found in the 3' untranslated region of the human dopamine transporter gene (DAT1) was scored in unrelated individuals drawn from 10 geographically widely dispersed populations in order to assess this marker's usefulness in human population genetics. The populations that were analyzed in this study included 4 indigenous groups of Siberia, natives of North and South America, as well as Caucasian and Oceanic groups, most of which represented small-scale societies. A total of 5 DAT1 alleles were seen overall, but only in one Siberian population, the Altai-Kizhi, were all 5 present, and in the Native Americans of Colombia the locus was monomorphic. The most common allele, DAT1*10, ranged in frequency from 52% in Greeks to 100% in South Americans. The high frequency of the DAT1*10 allele (approximately 90%) among Mongoloid groups of north and east Asia distinguishes them from most Caucasian groups. The presence of the rare DAT1*7 allele in relatively high frequency (approximately 5%) among all Siberian groups suggests a close affinity with north Asian groups, especially Mongolians. The presence of the even rarer DAT1*13 allele in one Siberian population, the Altai-Kizhi, reflects this group's long historical contact with Mongolians. The results demonstrated that the DAT1 VNTR polymorphism is useful in investigating population relationships, and that rare alleles at this locus may be particularly valuable in understanding the extent of genetic affinity between neighboring groups and in situations where admixture is suspected. However, because of both the association and linkage of this VNTR locus with attention-deficit hyperactivity disorder (ADHD) in children, and its highly restricted polymorphism (usually 3 alleles) in most human groups, the possibility of selection constraints on the DAT1 gene cannot be ignored.

Female↗
PubMed2000

Further data on the microsatellite locus D12S67 in worldwide populations: an unusual distribution of D12S67 alleles in Native Americans.

We report the frequencies of alleles at the microsatellite locus D12S67 in 2 widely separated ethnic groups of the world: 2 populations from Sulawesi, an island in the Indonesian archipelago, and 5 Native American tribes of Colombia, South America. The allele frequencies in the Minihasans and Torajans of Sulawesi are similar to each other (but the modal class allele is different) and in general agreement with those reported in mainland Asian groups, but different from both Europeans and Chinese Han of Taiwan. The 5 Native American tribes (Arsario, Kogui, Ijka, Wayuu, and Coreguaje) display different allele frequencies from those seen in Sulawesi populations, in other groups from Europe and mainland Asia, and in Chinese Han of Taiwan. Native Americans exhibit a bimodal distribution of alleles, unlike other groups, with significant differences among the tribes. The Arsario and Kogui have no admixture with Europeans or Africans and are the most distinctive, while the Wayuu have the most admixture and show most similarity to other groups. The data suggest that nonadmixed Native Americans may be quite distinctive with respect to this marker. The most common allele varies across the 5 tribes, from 249 base pairs to 261 base pairs. All samples exhibit Hardy-Weinberg genotype proportions; heterozygosities are lowest in the 2 nonadmixed Native American tribes. Examination of all the available data indicates that some east Asian and southeast Asian groups are characterized by a high frequency of smaller sized D12S67 alleles, while other populations have a greater proportion of the larger sized alleles. The cumulative, though still highly restricted, population data on locus D12S67 demonstrate that it may be of considerable value in anthropological genetic studies of ethnic groups. Data are required on Native Americans outside Colombia before this marker can be used in admixture studies of this group.

Base Pairing↗
PubMed1999

Deep common ancestry of indian and western-Eurasian mitochondrial DNA lineages.

About a fifth of the human gene pool belongs largely either to Indo-European or Dravidic speaking people inhabiting the Indian peninsula. The 'Caucasoid share' in their gene pool is thought to be related predominantly to the Indo-European speakers. A commonly held hypothesis, albeit not the only one, suggests a massive Indo-Aryan invasion to India some 4,000 years ago [1]. Recent limited analysis of maternally inherited mitochondrial DNA (mtDNA) of Indian populations has been interpreted as supporting this concept [2] [3]. Here, this interpretation is questioned. We found an extensive deep late Pleistocene genetic link between contemporary Europeans and Indians, provided by the mtDNA haplogroup U, which encompasses roughly a fifth of mtDNA lineages of both populations. Our estimate for this split is close to the suggested time for the peopling of Asia and the first expansion of anatomically modern humans in Eurasia [4] [5] [6] [7] [8] and likely pre-dates their spread to Europe. Only a small fraction of the 'Caucasoid-specific' mtDNA lineages found in Indian populations can be ascribed to a relatively recent admixture.

Animals↗
PubMed1999

Mitochondrial DNA deletion associated oxidative stress and severe male osteoporosis.

We have screened the mitochondrial genome of 15 men with symptomatic vertebral fractures (median age 62 years, range 27-72 years) and 17 male control subjects (median age 61 years, range 40-73 years) for the presence of mitochondrial DNA (mtDNA) deletions in peripheral monocyte DNA. Polymerase chain reaction analysis provided evidence of a common age-related (4.9 kb) mtDNA deletion situated between nucleotides 8470 and 13.460 of the genomic sequence in 5 of the 17 controls (29%) and 9 of the 15 patients (60%) investigated. Southern blotting and polymerase chain reaction revealed a novel 3.7 kb deletion in 2 patients. One of the affected patients, a 27-year-old man with severe osteoporosis (lumbar spine bone mineral density (BMD) 0.381 g/cm(2); Z-score -6.45) was found to harbor deletion in almost 50% of the mitochondria. The patient had a blood lactic acid level (4.6 nM) that was over 3 times the upper reference range (0-1.3 mM), thus confirming the presence of systemic oxidative stress. Further analysis by modified primer shift polymerase chain reaction showed the 5' breakpoint to be between the nucleotides 10.63 kb and 10.80 kb of the mtDNA. The second patient harboring the 3.7 kb deletion was older (62 years) with less severe osteoporosis (lumbar spine BMD 0.727/cm(2); Z-score -2.58) and the proportion of affected mitochondria was lower (25%). The significance of these findings is discussed and the possible relation between oxidative stress and accelerated bone loss is examined.

Adenoma, Chromophobe↗
PubMed1999

Vitamin D binding protein gene in male osteoporosis: association of plasma DBP and bone mineral density with (TAAA)(n)-Alu polymorphism in DBP.

Vitamin D binding protein (DBP) is a major carrier protein for the vitamin D metabolites, but may also play an important role in osteoclast differentiation. Polymorphisms of the DBP gene have been reported, including (TAAA)(n)-Alu repeat polymorphisms downstream of intron 8. We have examined the relationship between polymorphisms of the DBP gene and bone mineral density (BMD) and vertebral fractures in a group of 26 men with vertebral fractures but no underlying secondary cause of osteoporosis (median age 64, ages 27-72 years) and 21 male control subjects (median age 65, ages 40-77 years). There was no apparent effect of DBP phenotype on BMD, but there was a relationship between certain genotypes of (TAAA)(n)-Alu repeats and reduced BMD and vertebral fracture. Lumbar spine and femoral neck BMD were significantly lower in men with 10/8 genotype than 10/10 genotype (P < 0.05). Furthermore, the predominant genotype in men with vertebral fractures was 10/8, whereas the most common genotype in control subjects was 10/10 (odds ratio 56; 95% confidence interval 7-445). Plasma DBP was higher in men with 10/8 genotype than those with 10/10 genotype (P < 0.05), and patients with vertebral fractures were found to have higher levels than control subjects (P < 0.0005). Although our study is small because of the relative rarity of idiopathic osteoporosis in men, the results suggest that (TAAA)(n)-Alu polymorphism may have an important effect on plasma levels of DBP, bone density and fracture risk in men.

Adult↗
PubMed1999

Association of HLA-DRB1 alleles with giant cell tumour of bone.

AIM: To examine the possible influence of the MHC class II antigens alleles in the formation of the multinucleate aggressive giant cell tumour of bone. METHODS: HLA class II antigen alleles were investigated in eight white patients from north east England with confirmed diagnosis of giant cell tumour of bone. All had locally aggressive, immunophenotypically HLA-DR negative giant cell tumours. RESULTS: Five of the eight patients were found to be positive for HLA-DRB1*0801/3, the distribution of this allele in healthy white controls being quite low (2%). All but one of the patients possessing DRB1*080 also expressed DRB1*070. CONCLUSIONS: HLA-DRB1*080 is pre-dominant in patients with immunophenotypic HLA-DR negative giant cell tumour of bone; individuals with the genotype 070/080 are at particularly high risk of developing giant cell tumour of bone.

Alleles↗
PubMed1999

Deletion polymorphism in the human COL1A2 gene: genetic evidence of a non-African population whose descendants spread to all continents.

We report the frequencies of a deletion polymorphism at the alpha 2 (1) collagen gene (COL1A2) and argue that this distribution has major implications for understanding the evolution of modern humans immediately after their exodus from sub-Saharan Africa as well as their subsequent spread to all continents. The high frequency of the deletion in non-African populations and its complete absence in sub-Saharan African groups suggest that the deletion event occurred just before or shortly after modern humans left Africa. The deletion probably arose shortly after the African exodus in a group whose descendants were among the ancestors of all contemporary populations, except for sub-Saharan Africans. This, of course, does not imply that there was a single migration out of Africa. The GM immunoglobulin haplotype GM*A,X G displays a similar distribution to that for the COL1A2 deletion, and these 2 polymorphisms suggest that the exodus from Africa may not have been a rapid dispersion to all other regions of the world. Instead, it may have involved a period of time for the savanna-derived gene pool to adapt to novel selective agents, such as bacteria, viruses, and/or environmental xenobiotics found in both animal and plant foods in their new environment. In this context these polymorphisms are indicators of the evolution that occurred before the diaspora of these populations to the current distribution of modern peoples.

Africa South of the Sahara↗
PubMed1998

Age related somatic mitochondrial DNA deletions in bone.

BACKGROUND: It has been suggested that the accumulation of damage to mitochondrial DNA is a major cause of age related, degenerative disease. Aging is known to cause bone loss leading to a fall in bone mineral density and disruption of bone microarchitecture. However, despite the evidence of age related bone loss, no attempt has been made to detect specific deletions of mitochondrial DNA in the bone of aged individuals. AIMS: To detect bone specific, age related deletions in mitochondrial DNA. METHOD: Blood leucocytes and bone biopsies from patients who had undergone orthopaedic surgery were used as a source of mitochondrial DNA and screened for deletions using the polymerase chain reaction. RESULTS: Although no deletions were detected in the blood mitochondrial DNA, specific deletions in bone mitochondrial DNA were found in three of five elderly subjects. CONCLUSION: The findings of this study suggest that there could be a link between mitochondrial DNA deletions and free radical induced apoptosis of bone cells in the development of age related bone loss.

Adult↗
PubMed1998

Genetic variability of transferrin subtypes in the populations of India.

Five hundred fifteen samples from five populations of India (Brahmins, Marathas, Patels, and Parsees of western India and Hindus of Andhra Pradesh) were analyzed for transferrin subtypes using the isoelectric focusing technique. The allele frequencies of 8444 samples belonging to 93 populations of India have been tabulated, and data were analyzed for genetic diversity among geographic, regional, and socio-cultural groups. Three relatively common alleles, TF*C1, TF*C2, and TF*C3, showed wide variation in various populations of India. Compared with western India, a high frequency of the TF*C2 allele was observed in eastern India. This variation of the TF*C2 allele showed a geographic cline increasing from west to east, giving a significant positive correlation between the TF*C2 allele frequency and longitude. Various genetic processes that possibly maintain TF polymorphism are selection, admixture, genetic drift, and isolation by distance. The possible influence of various genetic processes is discussed.

Emigration and Immigration↗
PubMed1997

Vitamin D receptor gene polymorphism in men and its effect on bone density and calcium absorption.

OBJECTIVE: Previous studies have suggested that polymorphism of the alleles of the vitamin D receptor (VDR) gene may account for the major part of the heritable component of bone density in women, possibly mediated in part by impaired calcium absorption from the bowel. In view of the increasing importance of osteoporosis in men, we have now investigated the association between common allelic variations in the vitamin D receptor gene, calcium absorption and bone density in men. SUBJECTS: Forty-eight men (median age 64, range 27-77) with a wide range of bone density measurements, comprising 20 men with vertebral crush fractures and 28 male control subjects. MEASUREMENTS: Analysis of the VDR gene polymorphism and measurement of fractional radiocalcium absorption and bone mineral density was performed in all subjects. RESULTS: The distribution of the three genotypes (TT, tt, Tt) was comparable to that reported previously. There was no significant difference in femoral neck bone density Z-scores between the three genotypes (mean +/- SD TT -0.31 +/- 1.19, tt -0.08 +/- 1.28 and Tt -0.37 +/- 1.17). There were also no significant differences in mean femoral neck bone density T-scores or lumbar spine bone density Z or T-scores between the three genotypes. Fractional radiocalcium absorption was 0.59 +/- 0.27 for TT, 0.69 +/- 0.30 for tt and 0.60 +/- 0.30 for Tt, showing no significant difference between the genotypes. CONCLUSIONS: This study shows no association between vitamin D receptor gene polymorphism and bone density or fractional calcium absorption in a group of men with a range of bone density values. We conclude that the vitamin D receptor gene alleles probably account at most for only a small part of the genetic component of bone density in men.

Adult↗
PubMed1997

Genetic study of the tribal populations of Andhra Pradesh, south India.

Regional variation in the genetic constitution and genetic differentiation of three tribal populations (Koya, Lambadi, and Chenchu) of Andhra Pradesh, South India, was examined from the data of 27 polymorphic loci (9 blood groups, 13 red cell enzymes, and 5 serum proteins). Significant heterogeneity was observed among the three tribal groups at several loci (ABO, RH, P, ADA, PGM, ACP, ESD, PGD, GPT, HP, C3, and BF). Pairwise comparisons also showed significant genetic differences between the Koya and the Chenchu at seven loci, between the Koya and the Lambadi at nine loci, and between the Chenchu and the Lambadi at seven loci. Gene differentiation among the three tribes was sufficient to allow an overall excess of heterozygosity. The FIS estimates of each tribe showed positive values, but a great number of alleles showed negative FIS values, supporting varying degrees of gene flow and admixture with neighboring populations. The genetic differentiation and affinity of 14 tribal populations of Andhra Pradesh were further examined using published and unpublished data on 11 polymorphic genetic systems. Despite the genetic distinctions between two Chenchu samples and Koya and Koya-related tribes (Koya Dora and Konda Dora), geographic proximity seems to be an important determinant of affinity of the tribal populations of Andhra Pradesh. The extent of genetic diversity is high compared with previous reports from this state. No evidence from the present data indicates that selection had any appreciable effect on local differentiation, but the present analysis suggests that differences are more likely to be maintained by genetic drift, admixture, and inbreeding.

Ethnicity↗
PubMed1996

Reduced expression of HLA-B35 in schizophrenia.

The frequencies of HLA class I (HLA-A, B, C) and class II (HLA-DR, DQ) antigens were measured in 107 unrelated schizophrenic subjects and the results compared with 264 controls from south-east Scotland and a second control group of 133 individuals from north-east England. The expression of HLA-B35 was significantly reduced in the schizophrenic population compared to both control populations and these differences remained significant after correction for multiple testing. Linkage of schizophrenia and the major histocompatibility complex region of chromosome 6p was, however, excluded in a group of 17 families multiply affected with schizophrenia. Linkage was also excluded with several red cell antigens, red cell enzymes and plasma proteins. A negative association between the frequency of an HLA antigen and schizophrenia suggests that immune mechanisms may contribute to the aetiology of the disease in some subjects.

Adolescent↗
PubMed1996

HLA-DPB1 polymorphism in seven South American Indian tribes in Colombia.

HLA-DPB1 allele frequencies were investigated in seven geographically and linguistically distinct Amerindian tribes of Colombia. Allele *1301 was found only in the Embera tribe living along the Pacific coast, while allele *0101 was found only in two individuals of the Wayuu tribe inhabiting the Guajira desert. Significant geographical variation was observed in the other two alleles (*1401 and *0402), which were found in all seven tribal groups. The possible reasons for this restricted polymorphism and the genetic diversity found in the investigation are discussed.

Alleles↗
PubMed1996

HLA antigens in Ameridian groups of two different linguistic families from Colombia.

Serological HLA types (A, B, C, DR and DQ loci) were studied in five different Indian tribes (Cubeo, Tucano, Coreguaje, Embera and Noanama) belonging to two distinct linguistic families. For all the MHC loci, the range of variation among the five tribes was enormous. Two tribes, Cubeo and Tucano, showed a wide spectrum of antigenic specificities which seemed to be due to admixture from non-tribal groups, while in the other three tribes the polymorphisms of various HLA loci showed restricted distributions. The gene frequency data, when converted to a kinship matrix and a two-dimensional eigenvector plot, indicated that members of the same linguistic family tend to have greater genetic affinity.

Colombia↗