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Biomedical subjects

S S Papiha

Publications and source records attributed to S S Papiha.

At least 37 records · Page 2Linked to original sources

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

Origin of the Romany gypsies--genetic evidence.

Genetic heterogeneity and affinity was examined between nine Romany speaking gypsy populations and two of their possible ancestral populations from India. For AB0, Rhesus (D), MN and HP systems there exists a conclusive heterogeneity among these populations. Three gypsy populations from Western Europe (English, Welsh and Swedish) are genetically distinct from the rest of the East European gypsies and the populations of India analysed in this investigation. Overall the genetic differentiation among these populations is moderately high (RST = 0.029). The results also indicate the relative close relationship among the East gypsies and the two selected nomadic populations of India. The factors responsible for the moderate diversification of the East European gypsies may be high rate of migration, isolation and random drift, while among the Western gypsy populations admixture seems to be an important differentiation factor.

Adult

Mapping of the Darier's disease gene by serogenetic markers: results in two large British kindreds.

The authors have carried out genetic linkage studies in 57 subjects from two large kindreds of Darier's disease, using a range of serological and biochemical polymorphisms of known chromosomal location. In these kindreds, about 7% of the genome has been excluded for close linkage to the Darier's disease gene. However, one family showed positive lod scores for linkage with the Duffy blood locus (1p13); lod scores were negative in the other family, but in the combined families the total score for this marker was still positive and does not completely exclude linkage.

Chromosome Mapping

Population variation in molecular polymorphisms of the short arm of the human X chromosome.

Five DNA probes (RC8, 754, XJ 1-1, pert 87.8, and L1.28) from the short arm of the human X chromosome were investigated in samples from five populations (English, Nigerian, Chinese, Muslim, and Hindu from India). The variation in the allele frequencies of several probes between different groups was significant. The average heterozygosity in females of the five populations ranged from 32% to 51%. The genetic distance between the five groups was compatible with that using traditional polymorphic systems. There is an interesting suggestion of longitudinal cline for allele *2 (9 kb) detected with probe L1.28. The X-linked RFLPs are useful genetic markers for anthropological studies.

Alleles

Factor B (BF) allotypes and multiple sclerosis in north-east England.

A significant decrease in the frequency of BF*F allele and an increase of BF*F1 allele was found in 101 clinically definite multiple sclerosis patients compared to 270 normal controls from North-East England. In Dw2 types 41 patients and 60 controls, only the rare allele BF*F1 showed a significant increase in the patients group. For the common BF*S allele a significant increase was found in Dw2+ patients compared to the Dw2- patients, but a slight similar increase observed in Dw2+ controls did not attain significance. This increase in the patient group is attributed to a strong linkage disequilibrium between BF*S and Dw2 alleles. No such linkage disequilibrium exists in the normal controls. There is a suggestion that the BF*S and Dw2+ alleles are more prevalent in chronic progressive patients, implying that in Dw2+ patients BF may influence the progression of the disease.

Alleles

Serogenetic studies of the Lobanas in north-west India.

Phenotype and gene frequencies of several polymorphic genetic markers were examined in a Sikh agriculturist caste group, Lobanas of Punjab, India. Lobanas have been a trading community, now settled as cultivators, but for their origin there have been a difference of opinions. To trace their genetic relationship the gene frequency data was compared using multivariate analysis with several populations of India, which historically shared not only a common life style but also have a synonymous meaning of Lobana. The results of the study showed a conclusive genetic heterogeneity of Lobanas compared to the populations of North West and South India. While there is a suggestion that the differences in genetic structure of Lobanas may be due to their historical affiliation but the overall genetic diversity in this population may also be influenced by inbreeding, admixture and selection due to change in socio-economic factors.

ABO Blood-Group System