Study of enzyme polymorphism and haemoglobin patterns amongst sixteen tribal populations of central India (Orissa,Madhya Pradesh,and Maharashtra)

Summary A survey was conducted to study the genetic differentiation among 16 tribal groups of Orissa, Madhya Pradesh, and Maharashtra belonging to different ethnic and linguistic affiliations. Sixteen hundred and fifteen blood samples from both sexes were tested for 5 red cell enzyme systems: ACP, ESD, PGD, GLO, LDH, and Hb pattern. Three hundred and nineteen male individuals were tested for G-6-PD enzyme deficiency. The distribution of the enzyme markers and Hb show a range of variation which are more or less within the Indian range. Case of homozygous HbSS were detected in all the tribes except 3 tribes in Orissa. Two cases of LDH Cal-1 homozygote were found in two Dravidian language speaking Orissa tribes. The X²-values for testing the homogeneity of gene frequencies indicate a non-significant heterogeneity for all alleles in the individual system. Within population diversity seems to be larger than between population diversity. The degree of over all genetic differentiation as measured by G_ST value is 0.0154±0.0071.     

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.     

Diversity and Divergence Among the Tribal Populations of India

Tribal populations of the Indian subcontinent have been of longstanding interest to anthropologists and human geneticists. To investigate the relationship of Indian tribes to Indian castes and continental populations, we analyzed 45 unlinked autosomal STR loci in 9 tribal groups, 8 castes, and 18 populations from Africa, Europe and East Asia. South Indian tribal populations demonstrate low within‐population heterozygosity (range: 0.54 – 0.69), while tribal populations sampled further north and east have higher heterozygosity (range: 0.69 – 0.74). Genetic distance estimates show that tribal Indians are more closely related to caste Indians than to other major groups. Between‐tribe differentiation is high and exceeds that for eight sub‐Saharan African populations (4.8% vs. 3.7%). Telugu‐speaking populations are less differentiated than non‐Telugu speakers (F_ST: 0.029 vs. 0.079), but geographic distance was not predictive of genetic affinity between tribes. South Indian tribes show significant population structure, and individuals can be clustered statistically into groups that correspond with their tribal affiliation. These results are consistent with high levels of genetic drift and isolation in Indian tribal populations, particularly those of South India, and they imply that these populations may be potential candidates for linkage disequilibrium and association mapping.     

Immunoglobulin GM and KM genotypes in hepatitis C virus infection

Hepatitis C virus (HCV) is a major health problem, affecting over 170 million people worldwide. HCV causes a wide spectrum of liver disease, varying from persistent to asymptomatic infection. To evaluate the role of immunoglobulin (Ig) GM and KM genes in HCV infection, 191 HCV-infected Thai subjects were studied. These included 43 individuals with transient HCV infection and 148 individuals with persistent chronic HCV infection. The controls consisted of 134 healthy individuals. Several GM and KM alleles were determined by polymerase chain reaction-based methods. The frequency of G1M(f) homozygotes was lower (52.4% vs. 64.2%, P = 0.03) and the frequency of G1M(z) homozygotes was higher (10.5% vs. 3.7%, P = 0.02) in patients than the respective frequencies in controls. These results suggest that GM genotypes make a significant contribution to the risk of acquiring HCV infection.     

Serogenetic studies among an urban and two tribal populations of Orissa, India

Phenotype and gene frequencies of blood groups, plasma proteins and red cell enzymes (23 systems) are examined in two tribal and one low social class urban population of Orissa, India. Genetic heterogeneity is suggested not only between the tribal and urban populations but also between the tribal groups. The gene frequencies of tribal populations indicate a genepool with an ancestral component from the populations of north-east India with some mongoloid affinity, but it seems that there has also been some gene flow from them into the urban population.     

Immunoglobulin allotypes influence IgG antibody responses to hepatitis C virus envelope proteins E1 and E2

Immunoglobulin (Ig) GM and KM allotypes—genetic markers of γ and κ chains, respectively—are associated with the outcome of hepatitis C virus (HCV) infection, but the underlying mechanisms are not well understood. We hypothesized that GM and KM allotypes could contribute to the outcome of HCV infection by influencing the levels of IgG antibodies to the HCV glycoproteins E1E2. We serologically allotyped 100 African American individuals with persistent HCV infection for GM and KM markers and measured anti-E1E2 antibodies. Subjects with the GM 1,17 5,13 phenotype had significantly higher levels of anti-E1E2 antibodies than subjects who lacked this phenotype (p = 0.008). Likewise, subjects with the KM 1–carrying phenotypes had higher levels of anti-E1E2 antibodies than subjects who lacked these phenotypes (p = 0.041). Median titers were fourfold higher in persons expressing both GM 1,17 5,13 and KM 1–carrying phenotypes compared with those who lacked these phenotypes (p = 0.011). Interactive effects of these GM-KM phenotypes were previously found to be highly significantly associated with spontaneous HCV clearance. Results presented here show that Ig allotypes contribute to the interindividual differences in humoral immunity to the HCV epitopes, a finding that may provide a mechanistic explanation for their involvement in the outcome of HCV infection.     

Differential inhibition of trastuzumab- and cetuximab-induced cytotoxicity of cancer cells by immunoglobulin G1 expressing different GM allotypes

Antibody-dependent cell-mediated cytotoxicity (ADCC), which links the innate and the adaptive arms of immunity, is a major host immunosurveillance mechanism against tumours, as well as the leading mechanism underlying the clinical efficacy of therapeutic antibodies such as cetuximab and trastuzumab, which target tumour antigens, human epidermal growth factor receptor (HER)1 and HER2, respectively. Immunoglobulin (Ig)G antibody-mediated ADCC is triggered upon ligation of Fcγ receptor (FcγR) to the Fc region of IgG molecules. It follows that genetic variation in FcγR and Fc could contribute to the differences in the magnitude of ADCC. Genetic variation in FcγR is known to contribute to the differences in the magnitude of ADCC, but the contribution of natural genetic variation in Fc, GM allotypes, in this interaction has hitherto not been investigated. Using an ADCC inhibition assay, we show that IgG1 expressing the GM 3+, 1-, 2- allotypes was equally effective in inhibiting cetuximab- and trastuzumab-mediated ADCC of respective target cells, in the presence of natural killer (NK) cells expressing either valine or phenylalanine allele of FcγRIIIa. In contrast, IgG1 expressing the allelic GM 17+, 1+, 2+ allotypes was significantly more effective in inhibiting the ADCC - mediated by both monoclonal antibodies - when NK cells expressed the valine, rather than the phenylalanine, allele of FcγRIIIa. These findings have important implications for engineering antibodies (with human γ1 constant region) against malignancies characterized by the over-expression of tumour antigens HER1 and HER2 - especially for patients who, because of their FcγRIIIa genotype, are unlikely to benefit from the currently available therapeutics.     

Genetic variation at three VNTR loci in three tribal populations of Orissa,India

BACKGROUND: The variable number of tandem repeats (VNTR) loci are robust, simple and rapid tools for genetic characterization of both individuals and populations. This paper presents data on the distribution of three VNTRs (APOB, YNZ22 and D1S80) in three tribal populations (Gadaba, Kuvi-Khond and Paroja) of the Koraput district of Orissa, India with a view to enlarge our understanding of molecular genetic diversity among these tribes and the usage of these VNTRs in anthropogenetic studies. SUBJECTS AND METHODS: Three tribal populations were genotyped for APOB, YNZ22 and D1S80 loci using the polymerase chain reaction (PCR) technique. Gadaba are an Austro-Asiatic tribe while Kuvi-Khond and Paroja are Dravidian tribes. All samples were collected, with consent, from unrelated individuals. RESULTS: The observed allelic variation in these tribes is comparable with many Indian populations, but they showed significant overall and inter-population variability within the region. Allele *24 was the most common allele at the D1S80 locus in all populations, with Gadabas having the highest frequency (50%) followed by Paroja (32%) and Kuvi-Khond (23%). Gadabas also showed a higher frequency of allele *19 (13%) and *31 (9%) compared to other Indian and European populations. In the Apo B system, allele *37 was the most common in all three populations, with Gadabas having the highest frequency (39%) followed by Paroja (24%) and Kuvi-Khond (21%). This allele is present in high frequencies in other Indian (except Gonds) and European populations. Alleles *33 (17%), *35 (20%) and *45 (12%) were also common in the Gadabas, but Kuvi-Khond showed higher frequencies of *31(10%), *35(13%) and the larger allele *49(16%). Paroja, on the other hand, had higher frequencies of *31 (14%), *33 (17%) and *45 (13%). Allele *49 was also present in Paroja (10%) but was absent in the Gadaba. For the YNZ22 system, allele *4 was the most common in Kuvi-Khond (25%) and Paroja (21.4%), and allele *2 was the predominant allele in the Gadaba (33%). However allele *4 still occurs at relatively high frequency in Gadaba (27%). Allele *2 also occurs at relatively high frequency in Kuvi-Khond (20%) and intermediate frequency in Paroja (11%). Average heterozygosity was relatively low for Gadaba (0.7597 +/- 0.0191) and high for Kuvi-Khond (0.8618 +/- 0.0149) and Paroja (0.8512 +/- 0.0190), perhaps a reflection of effective population size and limitations to mating. The level of gene differentiation is, however, low (3-4%) for the three systems studied in these tribal populations and in data compiled from previous studies from the region. CONCLUSIONS: The VNTRs are polymorphic in the tribal populations studied and there is extensive allelic variation. Gadabas are isolated but Kuvi-Khond and Paroja show clear affinities with the Gonds, a major tribal group of Central India. Overall, allele frequency distribution, heterozygosity and genetic diversity analysis show that genetic diversity observed is socially, linguistically and geographically structured in this region.     

Molecular variants of G6PD deficiency among certain tribal communities of Orissa,India

This study investigated the extent of molecular heterogeneity of the G6PD enzyme among certain aboriginal (tribal) populations of Orissa, an eastern Indian state, which is hyperendemic for Plasmodium falciparum malaria. A total of 3480 males from 14 tribal communities were screened, and 223 (6.4%) individuals were found to be G6PD deficient. Molecular analysis revealed that 59.2% of deficient individuals had the G6PD Orissa mutation and 37.2% had the G6PD Mediterranean mutation. The presence of G6PD Med has not been previously reported among the tribal populations of Orissa. Interestingly, both G6PD Med and G6PD Orissa were found among communities belonging to the Mundari (Austroasiatic) linguistic group, while G6PD Med was exclusive to Dravidian and G6PD Orissa to Indo-Aryan groups. Erythrocytic G6PD enzyme activity was severely reduced in the case of G6PD Med type (0.64–1.1 IU/g Hb) as well as among the uncharacterized samples, but was moderate in G6PD Orissa type (1.2–3.1 IU/g Hb). Anaemia was moderate among the individuals with G6PD Med mutation and mild among individuals with G6PD Orissa mutations. The prevalence of G6PD deficiency as well as molecular variants of the Gd^– gene is highly heterogeneous among the tribal population of Orissa. The high endemicity of P. falciparum malaria has probably selected two different molecular variants of Gd^– at different points in time, which is discussed.     

Mitochondrial DNA variation and substructure among the tribal populations of Andhra Pradesh,India

We analyzed mtDNA HVR‐I variation among six tribal populations—Andh, Pardan, Gond, Naikpod, Kolam and Chenchu—from Andhra Pradesh. These tribes belong to the Dravidian and Indo‐European linguistic group. Except for Chenchu, the rest of the tribal samples were collected from two or more than two locations. The analysis of molecular variance (AMOVA) of the sequences yields a significant F_ST value (0.045), suggesting a fair degree of genetic differentiation among these tribes. When the tribal samples collected from different locations were considered as subpopulations in AMOVA, it is found that the variation among the subunits within the tribal groups is smaller than among the tribes. However, when Chenchu is removed from the analysis, the magnitude of within and between groups diversity becomes similar. In the multidimensional scaling plot based on F_ST distances the Chenchu is found to be the extreme outlier. Exclusion of Chenchu from AMOVA analysis and multidimensional scaling plot does not result in any specific pattern of population clustering. Mismatch distribution suggest that Chenchu might have undergone a bottleneck effect and does not show evidence of past demographic expansion as shown by the other five tribal groups. A comparison of AP tribes with some other caste and tribal populations of India suggests common maternal genetic heritage. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

IGHG, IGKC, and FCGR genes and endogenous antibody responses to GARP in patients with breast cancer and matched controls

Glycoprotein-A repetitions predominant (GARP) is a transmembrane protein that is highly expressed in breast cancer. Its overexpression correlates with worse survival, and antibodies to GARP appear to play a protective role in a mouse model. No large-scale studies of immunity to GARP in humans have yet been undertaken. In this investigation, using a large multiethnic cohort (1738 subjects), we aimed to determine whether the magnitude of anti-GARP antibody responsiveness was significantly different in patients with breast cancer from that in matched healthy controls. We also investigated whether the allelic variation at the immunoglobulin GM (γ marker), KM (κ marker), and Fcγ receptor (FcγR) loci contributed to the interindividual variability in anti-GARP IgG antibody levels. A combined analysis of all subjects showed that levels of anti-GARP antibodies were significantly higher in patients with breast cancer than in healthy controls (mean?±?SD: 7.4?±?3.5 vs. 6.9?±?3.5 absorbance units per mL (AU/μL), p?<?0.0001). In the two populations with the largest sample size, the probability of breast cancer generally increases as anti-GARP antibody levels increase. Several significant individual and epistatic effects of GM, KM, and FcγR genotypes on anti-GARP antibody responsiveness were noted in both patients and controls. These results, if confirmed by independent investigations, will aid in devising personalized GARP-based immunotherapeutic strategies against breast cancer and other GARP-overexpressing malignancies.     

The spectrum of haemoglobin variants in two scheduled tribes of Sundargarh district in north-western Orissa,India

Background: Tribal communities in India constitute a major part of the population and are vulnerable to many erythrocytic hereditary and haematological disorders such as haemoglobinopathies. Genetic studies so far undertaken on tribal groups are scanty, patchy and incomplete. No field-based systematic studies of hereditary haemolytic disorders in Orissa are available. Further, the extent of haemoglobin variants among the tribals in the state is not known. The present study was carried out in the Bhuyan and Kharia tribes of Sundargarh district in Orissa.

Aim: This study aims to find the prevalence/spectrum of haemoglobin variants in two major tribal groups, namely Bhuyan and Kharia and their subgroups, inhabiting the Sundargarh district in north-western Orissa.

Subjects and methods: Following the probability proportionate to size cluster sampling procedure for villages, a randomized sampling procedure was adopted irrespective of the age, sex and individual susceptibility pattern, selecting exclusive villages of each sub-group of tribes in five blocks. A total of 1603 blood samples of 836 Bhuyan and 767 Kharia tribals were screened for haemoglobin variants in the Sundargarh district of Orissa. Laboratory analyses of blood samples were carried out following standard procedures.

Results: The study showed a high prevalence of haemoglobin variants in the Bhuyan (9.8%) and Kharia (13.3%) tribes, sickle-cell disorders contributing 2.4% and 5.6%, respectively. The sickle-cell gene was found to be completely absent in the Dudh Kharia tribe, whereas the frequency in the Dhelki Kharia was quite high (12.5%). For the first time, 1.4% prevalence of haemoglobin E disorders (10 traits and one disease case) was recorded in a tribal population, i.e. Delki Kharia in Orissa. No other haemoglobin variant except β-thalassaemia trait was detected in the Dudh Kharia tribe (8.1%), showing their genetic isolation (p<0.001) from the Delki Kharia (4.1%), the average being 6.3% in the Kharia tribe. Out of three subgroups of Bhuyan studied, the sickle-cell trait was detected only in Paraja (0.9%) and Paik (7.4%), and not in Paudi (Hill) Bhuyans. However, the β-thalassaemia trait was detected in an average 6.5% in the Bhuyan tribe: in Paudi (2.1%), Paik (7.8%) and in Paraja (12.7%). For the first time in the tribes of Orissa a family was found with haemoglobin D trait (in Paik Bhuyan) and another with hereditary persistence of fetal haemoglobin (in Paraja Bhuyan). Clinical and haematological features of these disorders were similar to those reported in previous studies carried out in India.

Conclusion: Isolates of the Bhuyan and Kharia tribes show intra-group variations in prevalence of haemoglobin variants due to founder effect, genetic drift, and the practice of inbreeding in varied geographical and ecological niches in the Sundargarh district of Orissa.

Résumé. Arrière plan: Les communautés tribales de l’Inde forment la majeure part de sa population et sont vulnérables à de nombreuses affections érythrocytaires héréditaires ainsi qu’à des affections hématologiques telles que les hémoglobinopathies. Les études génétiques entreprises jusqu’alors sur des groupes tribaux sont rares, parcellaires et incomplètes. Aucune étude systématique des affections hémolytiques héréditaires fondée sur des données de terrain n’est disponible pour l’Orissa. De plus, l’étendue des variants de l’hémoglobine chez les membres de cette ethnie est inconnue. Le travail présenté a été effectué dans les tribus Bhuyan et Kharia du district de Sundargarh dans l’état de l’Orissa en Inde.

But: Cette étude cherche à définir la prévalence et le spectre des variants de l’hémoglobine dans deux groupes tribaux importants, Bhuyan et Kharia ainsi que dans leurs sous-groupes du district de Sundargarh dans la partie nord-ouest de l’Orissa.

Sujets et méthodes: On a adopté une procédure d’échantillonnage aléatoire définissant une probabilité proportionnelle à la taille des clusters villageois, indépendante de l’âge, du sexe et du profil de susceptibilité individuelle, en sélectionnant des villages exclusifs de chaque sous-groupe en cinq blocks. La recherche des variants de l’hémoglobine par les méthodes standard, a été effectuée sur un total de 1603 échantillons sanguins de 836 Bhuyan et 767 Kharia du district Sundargarh de l’Orissa.

Résultats: On trouve une forte prévalence de variants de l’hémoglobine dans les tribus Bhuyan (9,8%) et Kharia (13,3%), les sicklémies en représentant respectivement 2,4% et 5,6%. Le gène sicklémique est absent de la tribu Dudh Kharia alors que sa fréquence dans la tribu Dhelki Kharia est très élevée (12,5%). On a observé pour la première fois dans une population tribale (Dhelki Kharia) une prévalence de 1,4% des mutants de l’hémoglobine E (10 génotypes et un seul cas clinique). Aucune autre variante de l’hémoglobine à l’exception de la β-thalassaemia rencontré dans la tribu Dhudh Kharia (8,1%) n’a été trouvée, ce qui indique son isolement génétique (p<0,001) par rapport aux Dhelki Kharia (4,1%), la moyenne étant 6,3% chez les Kharia. Parmi les trois sous groupes Bhuyan étudiés, le trait drépanocytaire a été rencontré chez les Paraja (0,9%) et chez les Paik (7,4%) mais non chez les Paudi (petite montagne). Par contre le trait β-thalassémique est présent avec une moyenne de 6,5% chez les Bhuyan: (2,1%) chez les Paudi, (7,8%) chez les Paik et (12,7%) chez les Paraja. On a trouvé pour la première fois dans ces tribus de l’Orissa, une famille à hémoglobine D (chez des Paik Bhuyan) ainsi qu’une autre présentant une persistance héréditaire de l’hémoglobine foetale (chez les Paraja Bhuyan). Les caractéristiques cliniques et hématologiques de ces affections sont semblables à celles qui ont été décrites dans des études indiennes précédentes.

Conclusion: Les isolas des tribus Bhuyan et Kharia présentent des variations intra-groupes dans la prévalence des variants de l’hémoglobine provoqués par l’effet du fondateur et la dérive génique en association avec la pratique de mariages consanguins, dans diverses niches géographiques et écologiques du district de Sundargarh dans l’état indien de l’Orissa.

Zusammenfassung. Hintergrund: Stammesgemeinschaften in Indien stellen einen wesentlichen Teil der Bevölkerung und sind anfällig für zahlreiche erythrozytäre und hämatologische Erbkrankheiten wie z.B. Hämoglobinopathien. Bisher sind nur wenige genetische Untersuchungen in Stammesgemeinschaften durchgeführte worden. Systematische Feldstudien hämolytischer Erbkrankheiten gibt es in Orissa nicht. Zudem ist das Ausmaß an Hämoglobinvarianten bei Stämmen in diesem Bundesstaat nicht bekannt. Die vorliegende Studie wurde bei den Bhuyan und Kharia Stämmen des Sundargarhdistrikts von Orissa durchgeführt.

Ziel: Das Ziel dieser Studie ist, die Prävalenz/das Spektrum von Hämoglobinvarianten bei zwei größeren Stammesgruppen, insbesondere der Bhuyan und der Kharia und ihrer Untergruppen, die den Sundargarhdistrikt von Nordwest-Orissa bewohnen, zu bestimmen.

Probanden und Methoden: Gemäß der Wahrscheinlichkeit, die sich aufgrund von Größenverhältnissen bei Stichprobenerhebungen in Dörfern ergibt, wurde die Probandenerhebung randomisiert, unabhängig von Alter, Geschlecht und dem Muster an individueller Anfälligkeit, und es wurden ausschließlich Dörfer einer jeden Stammesuntergruppe in fünf Abschnitten gewählt. Insgesamt wurden 1603 Blutproben bei 836 Personen der Bhuyan- und bei 767 Personen der Kharia-Stämme auf Hämoglobinvarianten im Sundargarhdistrikt von Orissa untersucht. Die Laboruntersuchungen wurden nach Standardroutine durchgeführt.

Ergebnisse: Die Studie zeigte eine hohe Prävalenz an Hämoglobinvarianten bei den Bhuyan (9,8%) und bei den Kharia-Stämmen (13,3%), mit einem Anteil an Sichelzellerkrankungen von je 2,4%, bzw. 5,6%. Das Sichelzellgen fand sich überhaupt nicht bei Personen des Dudh Kharia-Stammes, während die Häufigkeit bei den Delki Kharia recht hoch war (12,5%). Zum ersten Mal wurde bei einer Stammesbevölkerung für eine Hämoglobin E-Erkrankung eine Prävalenz von 1,4% (10 Träger und eine manifeste Erkrankung) gezeigt, und zwar bei den Delki Kharia in Orissa. Abgesehen von der β-Thalassämie (8,1%) wurden weitere Hämoglobinvarianten bei den Dudh Karia nicht gefunden, was ihre genetische Isolation gegenüber den Delki Kharia (p<0,001) zeigt (4,1%), bei einer mittleren Häufigkeit von 6,3% bei den Kharia-Stämmen. Bei den drei untersuchten Untergruppen der Bhuyan wurden nur bei den Paraja (0,9%) und den Paik (7,4%), nicht aber bei den Paudi (Hill) Bhuyans Sichelzellträger gefunden. Allerdings wurden β-Thalassämieträger im Durchschnitt bei 6,5% der Personen des Bhuyan-Stammes gefunden, und zwar bei den Paudi (2,1%), den Paik (7,8%) und bei den Paraja (12,7%). Erstmals wurde bei den Stämmen in Orissa eine Familie mit Hämoglobin D gefunden (bei den Paik Bhuyan) und eine weitere mit genetischer Persistenz von fetalem Hämoglobin (bei den Paraja Bhuyan). Klinische und hämatologische Zeichen dieser Erkrankungen waren denen ähnlich, die in früheren Studien aus Indien bekannt geworden waren.

Zusammenfassung: Isolate der Bhuyan- und der Kharia-Stämme zeigen innerhalb der Gruppen Variationen der Prävalenz von Hämoglobinvarianten aufgrund von Gründereffekt, genetischer Drift und Inzucht in verschiedenen geographischen und ökologischen Nischen im Sundargarhdistrikt von Orissa.

Resumen. Antecedentes: En la India, las comunidades tribales constituyen una parte importante de la población y son vulnerables a muchos trastornos hematológicos y eritrocíticos hereditarios, como las hemoglobinopatías. Los estudios genéticos emprendidos hasta ahora sobre grupos tribales son escasos, poco uniformes e incompletos. No se dispone de estudios sistemáticos de campo sobre los trastornos hemolíticos hereditarios en Orissa. Además, se desconoce el número de variantes de la hemoglobina entre las tribus del estado. El presente estudio se realizó en las tribus Bhuyan y Kharia del distrito de Sundargarh, en Orissa.

Objetivo: Este estudio pretende encontrar la prevalencia/espectro de las variantes de la hemoglobina en dos grandes grupos tribales denominados Bhuyan y Kharia, y sus subgrupos, que residen en el distrito de Sundargarh, en el noroeste de Orissa.

Sujetos y Métodos: Para las aldeas, después de un procedimiento de muestreo de conglomerados, con probabilidades de inclusión proporcionales al tamaño, se adoptó un procedimiento de muestreo aleatorio independiente de la edad, sexo y patrón de susceptibilidad individual, seleccionando aldeas exclusivas de cada subgrupo de tribus en cinco bloques. Se analizó un total de 1603 muestras sanguíneas de 836 tribus Bhuyan y 767 tribus Kharia, con respecto a variantes de la hemoglobina en el distrito Sundargarh de Orissa. Los análisis de laboratorio de las muestras sanguíneas se realizaron siguiendo los procedimientos estándar.

Resultados: El estudio mostró una alta prevalencia de las variantes de la hemoglobina en las tribus Bhuyan (9,8%) y Kharia (13,3%), siendo la contribución de los trastornos de las células falciformes de un 2,4% y 5,6%, respectivamente. El gen de las células falciformes estaba completamente ausente en la tribu Dudh Kharia, mientras que su frecuencia en la tribu Dhelki Kharia era bastante alta (12,5%). Por primera vez se registró un 1,4% de prevalencia de trastornos de la hemoglobina E (10 rasgos y un caso de enfermedad) en una población tribal, la Delki Kharia en Orissa. No se detectó ninguna otra variante hemoglobínica, excepto el rasgo de la β-talasemia en la tribu Dudh Kharia (8,1%), mostrando su aislamiento genético (p<0,001) a partir de la Delki Kharia (4,1%), siendo el promedio en la tribu Kharia de un 6,3%. Fuera de los tres subgrupos de la tribu Bhuyan estudiados, el rasgo de las células falciformes se detectó únicamente en los Paraja (0,9%) y los Paik (7,4%), pero no en los Paudi (Hill) Bhuyans. Sin embargo, el rasgo de la β-talasemia se detectó en la tribu Bhuyan con un 6,5% de promedio: 2,1% en los Paudi, 7,8% en los Paik y 12,7% en los Paraja. Por primera vez en las tribus de Orissa se encontró una familia (en Paik Bhuyan) con el rasgo de la hemoglobina D y otra con una persistencia hereditaria de la hemoglobina fetal (en Paraja Bhuyan). Las características clínicas y hematológicas de estos trastornos eran similares a las señaladas en estudios previos realizados en la India.

Conclusión: Los aislados de las tribus Bhuyan y Kharia muestran variaciones intragrupales en la prevalencia de las variantes de la hemoglobina debidas al efecto fundador, a la deriva génica y a la práctica de la consanguinidad en nichos geográficos y ecológicos variados del distrito Sundargarh de Orissa.     

Quantification of human polyomavirus JC virus load in urine and blood samples of healthy tribal populations of North-Eastern part of West Bengal,India

Background: Human polyomavirus JC (JCV) is a widespread human virus with profound pathogenic potential. A study was undertaken to quantify JCV load in urine and peripheral blood samples of immunocompetent, apparently healthy tribal individuals of North-Eastern part of West Bengal, India for the first time. Materials and Methods: One hundred and thirteen samples of urine or blood were collected from different tribal groups of this region. For the quantitative estimation of the viral load in each sample, real-time polymerase chain reaction method using the SYBR Green dye was employed. Results: The viral load estimated was found in the range between 3.5 × 10² and 2.12 × 10⁶ copies/ml of samples having a mean and median viral copy numbers of 8.67 × 10⁵ and 9.19 × 10⁵ copies/ml of sample respectively. Conclusion: The mean viral DNA load in urine samples of the studied immunocompetent population was found to be higher than that found in a study conducted in the USA, but lower than similar groups of Italy and healthy adult women in the USA. However when compared with median values of viral DNA loads in urine samples of immunocompetent human subjects of Kuwait, Portugal, and Switzerland the observed viral DNA load was found to be substantially higher.     

Species distribution and physiological characterization of Acinetobacter genospecies from healthy human skin of tribal population in India

BACKGROUND: Various reports on distribution of Acinetobacter spp. from healthy human skin restricted to urban population. However, no such data is available from healthy human skin of tribal population not exposed to modern antibiotics during their life time. PURPOSE: Isolation, biotyping, distribution and physiological characterisation of Acinetobacter spp. from healthy human skin of tribal population. METHODS: Tribal population of Toranmal area of Satpuda Ranges, Maharashtra, India were sampled for ten body sites. Tentative Acinetobacter isolates were confirmed to the genus level by chromosomal DNA transformation assay and to species level using Bouvet and Grimont system. Novel physiological characteristics like pH, temperature and salt tolerance were studied. All strains were screened for production of various enzymes. RESULTS: One hundred and eighteen strains were isolated, which belonged to nine Acinetobacter genospecies. A. haemolyticus was most abundant followed by A. calcoaceticus and A. genospecies 1-3. Higher percentage of Acinetobacter was recovered from skin of nose, Pawara tribe and female volunteers. They showed wide variation in temperature, salt and pH tolerance. Most of the strains could produce enzymes viz, lipase, esterase, urease and amylase. CONCLUSIONS: Acinetobacter spp. belonging to nine genospecies were obtained in the present study. Physiological characteristics including high salt, temperature and acidic pH tolerance were helpful to differentiate between the commensal and pathogenic species of Acinetobacter genus.     

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

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

Human mtDNA hypervariable regions, HVR I and II, hint at deep common maternal founder and subsequent maternal gene flow in Indian population groups

We have analysed the hypervariable regions (HVR I and II) of human mitochondrial DNA (mtDNA) in individuals from Uttar Pradesh (UP), Bihar (BI) and Punjab (PUNJ), belonging to the Indo-European linguistic group, and from South India (SI), that have their linguistic roots in Dravidian language. Our analysis revealed the presence of known and novel mutations in both hypervariable regions in the studied population groups. Median joining network analyses based on mtDNA showed extensive overlap in mtDNA lineages despite the extensive cultural and linguistic diversity. MDS plot analysis based on Fst distances suggested increased maternal genetic proximity for the studied population groups compared with other world populations. Mismatch distribution curves, respective neighbour joining trees and other statistical analyses showed that there were significant expansions. The study revealed an ancient common ancestry for the studied population groups, most probably through common founder female lineage(s), and also indicated that human migrations occurred (maybe across and within the Indian subcontinent) even after the initial phase of female migration to India.     

Genetic variants of immunoglobulin γ and κ chains influence humoral immunity to the cancer‐testis antigen XAGE‐1b (GAGED2a) in patients with non‐small cell lung cancer

GM (γ marker) allotypes, genetic variants of immunoglobulin γ chains, have been reported to be associated strongly with susceptibility to lung cancer, but the mechanism(s) underlying this association is not known. One mechanism could involve their contribution to humoral immunity to lung tumour‐associated antigens. In this study, we aimed to determine whether particular GM and KM (κ marker) allotypes were associated with antibody responsiveness to XAGE‐1b, a highly immunogenic lung tumour‐associated cancer‐testis antigen. Sera from 89 patients with non‐small cell lung cancer (NSCLC) were allotyped for eight GM and two KM determinants and characterized for antibodies to a synthetic XAGE‐1b protein. The distribution of various GM phenotypes was significantly different between XAGE‐1b antibody‐positive and ‐negative patients (P = 0·023), as well as in the subgroup of XAGE‐1b antigen‐positive advanced NSCLC (P = 0·007). None of the patients with the GM 1,17 21 phenotype was positive for the XAGE‐1b antibody. In patients with antigen‐positive advanced disease, the prevalence of GM 1,2,17 21 was significantly higher in the antibody‐positive group than in those who lacked the XAGE‐1b antibody (P = 0·026). This phenotype also interacted with a particular KM phenotype: subjects with GM 1,2,17 21 and KM 3,3 phenotypes were almost four times (odds ratio = 3·8) as likely to be positive for the XAGE‐1b antibody as the subjects who lacked these phenotypes. This is the first report presenting evidence for the involvement of immunoglobulin allotypes in immunity to a cancer‐testis antigen, which has important implications for XAGE‐1b‐based immunotherapeutic interventions in lung adenocarcinoma.     

Perceptions and preferences of medical students regarding teaching methods in a Medical College,Mangalore India

Introduction

In the complex setting of a medical school it becomes essential to utilize an approach to teaching and learning that is best suited to the needs of the students. In developing countries like India, where there is an exponential increase of institutions catering to medical students, it becomes a challenge to teach to large number of students per class. Hence, research is needed to identify the needs of students in relation to their day to day learning activities.

Objectives

To understand the preferences and perception of medical students about the current methods of teaching, aids used for teaching and also identify barriers in learning as perceived by the students.

Method

A Cross-sectional study was carried out at Kasturba Medical College, Mangalore during May 2012. Study participants included 2^nd and 3^rd year medical students. A semi-structured questionnaire was used to collect the information in relation to preferences and perceptions regarding teaching methods utilized for theory and clinical teaching. SPSS version 11.5 was used for analysis of data. The association between variables of interest was tested using Chi-square test.

Results

A total of 286 students (56.6 % females and 43.4% males) participated with a dropout rate of 10.6%. The study revealed that 71.3% of the students had an attendance above 75%. The most preferred teaching method was Problem Based Learning (PBL) (71.4%) as students felt that it enhanced lateral thinking while Didactic Lectures was the least preferred (32.8%). The most preferred modality of teaching aid was found to be Black board preferred by 46.9% students. In learning rare signs and cases, students preferred video lectures (41%) and mannequins (75.9%) in learning clinical skills. The main barrier in theory learning identified was inappropriate teaching methods (15%) and being new to clinical posting (38.5%) in case of learning clinical skills.

Conclusion

The findings of the study suggest that a combination of traditional methods with other methods such as PBL, video lectures and mannequins could be an effective way of teaching theory and clinical skills.