The first 25 years of human genetics in Newcastle.
Explore the source record for details and available documents.
England↗
Biomedical subjects
S S Papiha
Publications and source records attributed to S S Papiha.
Genetic variation in India.
In the last 25 years a number of genetic studies on the populations of the Indian subcontinent have been conducted. Unfortunately, most of the studies covered a limited number of genetic systems, and only a few provide information on the genetic differentiation and population structure of some regional caste, tribal, religious, and urban groups. Despite a recent report suggesting that in eastern India genetic affinity does not show any large degree of congruence with sociocultural hierarchy, three distinct surveys reported here indicate that geographic proximity, ethnohistory, and biosocial and cultural affiliation are important determinants of genetic affinity. Gene differentiation studies are few, but from the information of some previous papers and results presented in this special issue of Human Biology, the pattern of differentiation is becoming clear. In general, genetic differentiation in populations of India is low (0.26-1.7%), but overall genetic differentiation in 18 mixed populations of India is higher (2.23%), similar to the largest single study on 16 tribal groups from central India (2.18%). The tribal population of South India shows the highest FST value (4.1%), and this value is similar to a study of the Dhangar caste group. The reason for this high FST value is not clear. One possibility may be (semi-) isolation associated with such factors as random inbreeding and drift, which can cause high levels of genetic differentiation among the tribal groups of India and among the castes such as Dhangar. However, further studies are needed to explore the causes of such high values of genetic differentiation, especially in these populations.
Ethnicity↗
Variability of genetic markers in Himachal Pradesh, India: variation among the subpopulations.
The genetic composition of one tribal and two nontribal populations of the Chamba District, Himachal Pradesh, India, was studied by phenotype analyses of 25 genetic markers (9 blood groups, 13 red cell enzymes, and 3 serum proteins). Furthermore, the genetic structure of 11 populations from 3 districts, Chamba, Kangra, and Kinnaur of Himachal Pradesh, was also analyzed using data from 20 loci (57 alleles). Nine genetic systems (ABO, Rh, FY, P, PGM, ACP, AK, PGD, and HP) showed highly significant heterogeneity in the five populations of Kinnaur District, whereas among the six populations from Chamba and Kangra districts the genetic variation was low. The FIS value at each locus for the five populations of Kinnaur District and the six populations from Chambra and Kangra districts was consistently higher than the FST estimates, suggesting that the population structure of both regions is influenced by local random inbreeding. Although the role of selection in local genetic differentiation cannot be ruled out, the present analyses indicate that local differentiation is mainly affected by geographic proximity, random inbreeding, and admixture.
Ethnicity↗
Genetic differentiation and population structure of some occupational caste groups in Uttar Pradesh, India.
Phenotypes and gene frequencies of 24 genetic markers (9 blood groups, 11 red cell enzymes, and 4 serum proteins) were investigated in 5 occupational caste groups (Brahmin, Khatri, Vaish, Kayastha, and scheduled castes) and 1 religious group of Muslims in Uttar Pradesh, India. This is the first extensive genetic study in Uttar Pradesh that establishes the range of genetic variation in different endogamous groups. The extent of genetic variation among different occupational caste groups is low, and only two genetic systems (C3 and ACP) showed heterogeneity. The genetic affinity analysis showed an unexpected close affinity of scheduled castes with the Khatri. This observation warrants further analysis of these groups, but the present results may be a chance finding resulting from the nature of the samples, which represent individuals from vastly different regions of Uttar Pradesh. The affinity of the Muslim group with other caste groups suggests that the samples may include descendants of converts from the seventeenth century who are still at an early stage of differentiation. The FST estimate for the populations is 0.009, which is close to other estimates reported from north and northwest India. The overall mean FIS value is 0.066, and for each locus the FIS estimate is considerably higher than the FST estimate, suggesting that the infrastructure of the populations is influenced by nonrandom mating (inbreeding). There is no evidence of any disruptive selection, but the allele frequency of each caste group of Uttar Pradesh must be affected by its large population size, which, because of chance migration of individuals with different gene frequencies, would accentuate genetic differences.
Ethnicity↗
Population structure and genetic differentiation among 16 tribal populations of central India.
Genetic polymorphisms for six blood groups, three red cell enzymes, three serum proteins, and hemoglobin were examined in sixteen central Indian tribal populations. Nine of the tribes belonged to Orissa, five to Madhya Pradesh, and two to Maharashtra. Eleven tribes spoke the Dravidian language, three Indo-Ayran, and two the language of the Austro-Asiatic families. The population structure of these tribal populations was analyzed at the inter- and intrastate and linguistic levels, using data for 13 genetic systems (38 alleles or haplotypes). Nine of the 13 loci showed significant heterogeneity in the 16 tribes, and the pattern of heterogeneity was also discernible in the different states and in the Dravidian-speaking tribes. As expected, the extent of genetic differentiation or gene diversity was the highest so far reported from central India. The mean FIS and HS for each locus in the different state, linguistic, and total tribal groups were consistently higher than the FST and GST values, respectively, showing that the genetic structure of each tribe is highly influenced by inbreeding. In a genetic affinity analysis by genetic distance the Indo-Aryan and Austro-Asiatic language groups showed little affinity with each other, although there was some tendency toward geographic affinity. The present analysis indicates that, in addition to genetic drift, gene flow, and selection, the genetic structure of the populations of central India is also highly influenced by sociocultural adaptation and inbreeding.
Ethnicity↗
Genetic variation in Sri Lanka.
A population genetic study was designed to analyze genetic composition and population structure of the five main population groups (Sinhalese, Tamils, Moors, Burghers, and Malays) of Sri Lanka. Twentyseven polymorphic and three monomorphic loci were examined in all five populations. Several genetic markers, including subtype variation of HP, TF, PI, GC, ORM, and PGM1, were analyzed for the first time and helped to clarify the range of genetic variation for Sri Lankan populations. Many genetic systems (Rh, JK, ACP, ESD, HP, C3, TF, and GC) showed a high level of variation among the populations of Sri Lanka. However, at the individual level the Burgher population (a hybrid group between the Dutch and Portuguese and the local Sinhalese) showed European features, but its gene frequencies were either intermediate to its parental populations or more similar to the local Sinhalese. In the F statistic analysis all populations showed positive FIS values, ranging from 0.0305 in the Burghers to 0.1084 in the Malays; however, for a large number of loci the FIS values for the Burghers were negative, indicating the possible hybrid nature of this population. In genetic affinity studies the Burghers, Moors, and Malays showed a greater degree of isolation, but compared with the possible populations of their origin, the five populations of Sri Lanka tended to show some degree of affinity to each other. Our analysis therefore suggests that there is little evidence of disruptive selection; however, restricted gene flow favors the change of allele frequency toward the local Sinhalese and Tamil populations.
Ethnicity↗
Restriction fragment length polymorphism of HLA-DR and HLA-DQ allotypes in four endogamous groups of western India.
HLA-DR and HLA-DQ allele frequencies in four populations (Brahmin, Maratha, Gujarati Hindu Patel, and Parsi) of Bombay, western India, were analyzed using TaqI RFLPs detected by the cDNA probes DRB, DQB, and DQA. Although the overall differences in the HLA-DR and HLA-DQ genotype frequencies among the populations were not statistically significant, several population-specific haplotypes were significant. Multivariate analyses using data on 2 loci (HLA-DR and HLA-DQ) produced a meaningful pattern of genetic affinity and differentiation that parallels the analysis made when frequency data on 23 loci (21 blood group and protein loci and 2 class II antigen loci) are used. The RST for class II loci was 0.006; the genetic differentiation increased to 0.01 when data on 23 polymorphic loci were analyzed. The genetic affinity analysis shows the isolated nature of the Parsi and close genetic affinity between the two local populations of Bombay. Although the RFLP technique has several limitations compared with newly defined PCR-based methods, our analysis shows that the RFLP technique is still a useful adjunct method for studying HLA polymorphisms for which only limited data from the populations of the Indian subcontinent are available.
Consanguinity↗
Complement components C2, C3, and C4 (C4A and C4B) and BF polymorphisms in populations of the Indian subcontinent.
Genetic polymorphisms of the complement components (five loci: C2, C3, C4A, C4B, and BF) have been investigated in the Telugu-speaking Hindu population of Hyderabad, Andhra Pradesh, India, and the Bangali-speaking Muslim population of Dacca, Bangladesh. The available data are compared to understand the genetic variation of complement components in populations of the Indian subcontinent. The C3*F and BF*F alleles show wide frequency variations in different ethnic groups of India. The range of variation in the C3*F allele is intermediate between European whites and southeast Asian populations, whereas the BF*F allele places the Indian frequencies between European whites and African blacks. This is the first population study to investigate the C2 and C4 (C4A and C4B) polymorphisms in two distinct groups of the Indian subcontinent. For the C2 polymorphism only the C2*B variant allele was observed, and its frequency was slightly higher than in European populations. In both populations the C4A and C4B loci were highly polymorphic, with a high frequency of the null alleles C4A*QO and C4B*QO, which may account for the greater susceptibility to certain autoimmune diseases in populations of South Asia.
Bangladesh↗
Immunoglobulin allotypes and estimation of genetic admixture among populations of Kinnaur District, Himachal Pradesh, India.
Four regional populations of the Kanet (Puh, Kalpa, Sangla, and Nachar) and an endogamous group of Koli from Kinnaur District, Himachal Pradesh, India, were studied to determine the extent of genetic variation of immunoglobulin allotypes (GM, KM, and AM) and the genetic contribution from ancestral populations of Tibet and northwest India. Haplotype GM*A G showed a higher frequency in the Kanet (40-60%)-a frequency that is more comparable to Asian populations-whereas in the Koli a lower frequency was observed, which is nearer the values for populations from northwest India. The IG haplotype data suggest that the Kanet population of Kinnaur District and the northeastern population of Nepal have different European origins than the more central population of India, represented by a sample from Delhi. The present results suggest that the populations of Kinnaur District are of admixed origin with contributions of Tibetan genes of 87.3%, 51.3%, 49.9%, 40.0%, and 9.5% in the Puh, Kalpa, Sangla, and Nachar Kanet and the Koli, respectively. The genetic distance obtained from 19 loci (9 blood groups, 8 biochemical markers, GM, and KM) showed an inverse relationship between the distance of the hybrid population from the parental gene pool. The Puh Kanet, nearest the Tibetan border, had the highest proportion of Tibetan genes but showed the lowest genetic distance with Tibetans. As the geographic distance of the other regional populations of the Kanet increases from the border of Tibet, genetic distance compared with the parental Tibetan population increases and the proportion of Tibetan admixture decreases. In the Kinnaur District admixture seems to contribute largely to the present-day observed high level of genetic differentiation.
Ethnicity↗
New rare variants and interpretation of the genetic diversity at the group-specific component (GC) locus in populations of India.
As part of our ongoing genetic studies, 2635 samples from 30 populations of the Indian subcontinent have been analyzed for GC subtype variation. Several rare variants were found and have been characterized using isoelectric focusing in 3 M urea and with an immobilized pH gradient and by comparison with known standards. Six new variants, 1A33, 2A22, 2A23, 2A24, 1C56, and 1C59, have been discovered in geographically and ethnically distant populations of the Indian subcontinent. Variants 1C11 and 1C21 have been reported previously in the French population and variant 1C36 has been reported in Nepalis, but all three variants were observed for the first time in the populations of India. The distribution of the rare variants in the Indian subcontinent was examined for anthropological usefulness for differentiation of Indian populations. The data for GC allele frequencies from 144 populations of India were compared for geographic and ethnic variation. A high frequency of the GC*IF allele was observed in populations of eastern India, and various ethnic groups from the eastern zone were clearly differentiated from similar ethnic populations from the rest of India. GC*2 allele frequency data were further correlated with various geographic and climatic variables, such as longitude, latitude, sunshine, solar radiation, and mean annual temperature. A significant positive correlation between GC*2 frequency and latitude was observed. The GC*2 allele frequency showed a cline increasing from south to north. Significant negative correlation was also observed between GC*2 frequency and sunshine, solar radiation, and mean temperature. A possible interpretation for selection of the GC*2 allele in areas with low levels of insolation is provided.
Climate↗
Population genetic study of three VNTR loci (D2S44, D7S22, and D12S11) in five ethnically defined populations of the Indian subcontinent.
Using RFLP (restriction fragment length polymorphism) analysis, we have characterized the genotypic variation of three VNTR (variable number of tandem repeat) loci (D2S44, D7S22, and D12S11) with probes YNH24, g3, and MS43a, respectively, for 288 individuals from 5 genetically well-defined ethnic groups (Brahmins, Maratha, Gujarati Patel, Sinhalese, and Moors) of the Indian subcontinent. The distributions of VNTR alleles at the binned level were examined among the five populations, and the genetic affinities obtained using the VNTR data were compared with serogenetic data on 22 blood group and protein loci previously reported from our laboratory. For classical genetic markers the Sinhalese show slight affinity with the populations of western India. However, the genetic affinity results considerably parallel the results for VNTR loci and 25 combined VNTR/blood group/protein loci, suggesting that the Sinhalese show the least affinity with the populations of western India. These results confirm the findings of a recent study of genetic relationships of the populations of Sri Lanka based on admixture analysis. The concerns regarding whether or not the pattern of genetic variation of VNTR loci at the bin level can be studied using classical population principles are addressed.
Ethnicity↗
Allotypes of complement components C4, C3, C2 and BF in the populations of Tasmania and northeast England.
The distribution of four serum complement component polymorphisms (BF, C2, C3 and C4) were examined in two geographically separated populations, one from Tasmania (Australia) and the other from northeast England. The differences in genotypic frequencies between them at all 4 loci are not statistically significant (p > 0.05). When C4 haplotypes were investigated, only one (C4A4-C4B2) exhibited significant linkage disequilibrium (p = 0.0006 after correction, p = 0.01), and this was only observed in Tasmanians. The English population exhibited a larger number of alleles across the four loci used in this study than the Tasmanian, and this may well reflect a bottle-neck effect and the greater relative isolation of the population of the island State of Australia. Overall, the findings confirm the close relationship between immigrants from the British Isles to Tasmania.
Complement C2↗
Oligonucleotide (CAC)5 fingerprinting: validity and reliability in paternity testing.
Following the development of DNA fingerprinting (Jeffreys et al., Nature 1985, 314, 67-73) using the minisatellite probes 33.15 and 33.6, many other fingerprinting probes have been described. The wide type M13 phage, 3' HVR region of alpha globin gene, F10 and various synthetic oligonucleotide probes have been shown to produce multiallelic and individual specific DNA fingerprints. The two probes developed by Jeffreys et al. have been extensively used in forensic and paternity determination in various laboratories, however, for the use of DNA fingerprints produced by synthetic oligonucleotide probes, still need critical evaluation. In this paper the statistical evaluations of the fingerprinting probes (CAC)5 was carried out by comparing the results produced by Jeffreys et al., using probes 33.15 and 33.6. The mutation rate calculated for (CAC)5 as 0.015 is nearly similar to the probe 33.15 (0.011) but higher than the probe 33.6 (0.005). The data obtained using (CAC)5 fingerprint in paternity cases from the northeast of England are presented.
DNA Fingerprinting↗
Distribution of group specific component (GC) and transferrin (TF) subtypes in populations of Sri Lanka.
A random sample of 503 individuals from five endogamous groups of Sri Lanka was studied for the genetic polymorphism of the group specific component (GC) and transferrin (TF) using isoelectric focusing. Both systems showed statistically significant heterogeneity among the five main populations of the island. The GC allele frequencies of Malays are significantly different from those of the other four populations (Sinhalese, Tamils, Moors and Burghers). However, the TF system shows less variation, since only the Moors show a significant heterogeneity compared to Tamils and Burghers. The frequencies found in the present study are very different from those reported for the populations of the Indian mainland.
Alleles↗
Serogenetic analysis in the study of the population structure of the eastern Adriatic (Croatia).
The anthropogenetic structure of six island and peninsular populations (Brac, Hvar, Korcula, Peljesac, Silba, and Olib) of the eastern Adriatic, Croatia, is analyzed on the basis of the study of four different erythrocyte antigen systems or groups (ABO, Rhesus, Kell-Celano, P) and two erythrocyte isoenzyme systems (ACP, ESD). The average sample size was 555 individuals. Allele frequencies, genetic distances, and gene diversity values were computed. The results indicate that all the populations in question have preserved their separate characteristics over the course of their (micro)evolution to the present day; this is especially noticeable for the island populations of Korcula and Olib, as these are distinguished from the other four populations by a greater degree of isolation. Today's genetic structure of the six populations can be explained through the existing historical and cultural data for the region in question, which indicate that over the course of their ethnohistory they were all influenced by significant waves of immigration and selective emigrations that must have greatly shaped their present-day population structure.
Alleles↗
Genetic polymorphism of orosomucoid (ORM) in populations of the United Kingdom, Indian subcontinent, and Cambodia.
The genetic variation of the human serum orosomucoid (ORM) was investigated by isoelectric focusing (IEF) followed by immunofixation in 15 different populations from East Midlands (United Kingdom), India, Sri Lanka, and Cambodia. Statistically significant differences were observed between various Asiatic and British populations, however differences within Asiatic and European populations were minor. The distribution of ORM1 alleles in populations investigated to date suggests an interesting east-west geographical cline. There is a suggestion that present day wide polymorphism at the ORM1 locus may be influenced by selection.
Alleles↗
PGM1 subtypes in populations of the Indian subcontinent.
Isoelectric focusing was performed to analyze PGM1 polymorphism in six tribal, five caste, and five Muslim populations from the Indian subcontinent. Although a considerable range of allele frequencies was observed in certain caste and Muslim groups, the phenotypic distribution showed significant genetic heterogeneity only among the tribal groups. Discriminant analysis suggests that the PGM1 locus provides useful anthropogenetic information to differentiate the populations of the subcontinent in terms of their social structure. In the three population groups studied the variation in the heterozygosity levels suggests that the genetic diversity at the PGM1 locus may be the result of the structure of various population groups.
Discriminant Analysis↗
Association of Wegener's granulomatosis with HLA antigens and other genetic markers.
The frequencies of the HLA-A, B, C, DR, DQ antigens and of several other genetic markers in biopsy proved and well characterised patients with Wegener's granulomatosis were compared with control frequencies of the region. A highly significant increase in HLA-DR1 was found. The percentage combined frequency of DR1-DQw1 was significantly higher in patients than in the controls. Interestingly, association with the red cell enzyme GLOI and complement locus C4B was also seen. As both of these markers are either linked or within the major histocompatibility complex region (MHC) this is further evidence for the involvement of chromosome 6 in the pathogenesis of Wegener's granulomatosis. To understand the pathology of the disease fully molecular genetic studies of the MHC region are warranted.
Adult↗