Taruna Madan

The Indian Genome Variation database (IGVdb): A project overview

Indian population, comprising of more than a billion people, consists of 4693 communities with several thousands of endogamous groups, 325 functioning languages and 25 scripts. To address the questions related to ethnic diversity, migrations, founder populations, predisposition to complex disorders or pharmacogenomics, one needs to understand the diversity and relatedness at the genetic level in such a diverse population. In this backdrop, six constituent laboratories of the Council of Scientific and Industrial Research (CSIR), with funding from the Government of India, initiated a network program on predictive medicine using repeats and single nucleotide polymorphisms. The Indian Genome Variation (IGV) consortium aims to provide data on validated SNPs and repeats, both novel and reported, along with gene duplications, in over a thousand genes, in 15,000 individuals drawn from Indian subpopulations. These genes have been selected on the basis of their relevance as functional and positional candidates in many common diseases including genes relevant to pharmacogenomics. This is the first large-scale comprehensive study of the structure of the Indian population with wide-reaching implications. A comprehensive platform for Indian Genome Variation (IGV) data management, analysis and creation of IGVdb portal has also been developed. The samples are being collected following ethical guidelines of Indian Council of Medical Research (ICMR) and Department of Biotechnology (DBT), India. This paper reveals the structure of the IGV project highlighting its various aspects like genesis, objectives, strategies for selection of genes, identification of the Indian subpopulations, collection of samples and discovery and validation of genetic markers, data analysis and monitoring as well as the project’s data release policy.Indian population, comprising of more than a billion people, consists of 4693 communities with several thousands of endogamous groups, 325 functioning languages and 25 scripts. To address the questions related to ethnic diversity, migrations, founder populations, predisposition to complex disorders or pharmacogenomics, one needs to understand the diversity and relatedness at the genetic level in such a diverse population. In this backdrop, six constituent laboratories of the Council of Scientific and Industrial Research (CSIR), with funding from the Government of India, initiated a network program on predictive medicine using repeats and single nucleotide polymorphisms. The Indian Genome Variation (IGV) consortium aims to provide data on validated SNPs and repeats, both novel and reported, along with gene duplications, in over a thousand genes, in 15,000 individuals drawn from Indian subpopulations. These genes have been selected on the basis of their relevance as functional and positional candidates in many common diseases including genes relevant to pharmacogenomics. This is the first large-scale comprehensive study of the structure of the Indian population with wide-reaching implications. A comprehensive platform for Indian Genome Variation (IGV) data management, analysis and creation of IGVdb portal has also been developed. The samples are being collected following ethical guidelines of Indian Council of Medical Research (ICMR) and Department of Biotechnology (DBT), India. This paper reveals the structure of the IGV project highlighting its various aspects like genesis, objectives, strategies for selection of genes, identification of the Indian subpopulations, collection of samples and discovery and validation of genetic markers, data analysis and monitoring as well as the project’s data release policy.

Protective Roles of Pulmonary Surfactant Proteins, SP-A and SP-D, Against Lung Allergy and Infection Caused by Aspergillus fumigatus

Pulmonary surfactant proteins, SP-A and SP-D, are immune molecules which can directly interact with pathogens and allergens, stimulate immune cells and manipulate cytokine and chemokine profiles during hosts immune response. Using an opportunistic fungal pathogen Aspergillus fumigatus (Afu), we have attempted to understand participation of SP-A and SP-D in the host immunity. Afu causes a systemic infection via lungs, called invasive aspergillosis (IPA) in immunocompromised subjects. In the immunocompetent subjects, it can cause an allergic disorder, called allergic bronchopulmonary aspergillosis (ABPA). Therapeutic administration of these proteins in a murine model of IPA can rescue mice from death. Treating mice, having ABPA, can suppress IgE levels, eosinophilia, pulmonary cellular infiltration and cause a marked shift from a pathogenic Th2 to a protective Th1 cytokine profile. These results highlight the potential of SP-A, SP-D and their recombinant forms, as novel therapeutics for lung allergy and infection.

Characterization of glycoprotein antigen (45 kD) of Aspergillus fumigatus

Abstract An immunodominant glycoprotein antigen (45 kD) from Aspergillus fumigatus was purified and characterized. The purified antigen exhibited strong precipitin reaction with the sera of allergic bronchopulmonary aspergillosis (ABPA) patients. Enzyme-linked immunosorbent assay (ELISA) and Western blot results revealed strong binding of gp 45 with IgG and IgE antibodies of ABPA patients. Three monoclonals of IgM isotype, raised against a glycoprotein fraction of A. fumigatus , recognized 45 and 55 kD antigens. These results suggest the presence of common epitopes in these antigens. The protein to carbohydrate ratio of purified antigen was observed to be 1.4: 1.0. Further analysis by gas liquid chromatography revealed the presence of glucose, mannose and glucosamine residues in a 4 : 3 : 1 ratio. Deglycosylation of N-linked sugars of gp 45 with N-glycosidase-F resulted in a 27 kD band on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Neuraminidase treatment destroyed the IgE binding activity of the antigen but IgG binding activity was retained. The IgG binding activity on the other hand was lost on treatment with pronase. The major IgG binding epitope of this glycoprotein antigen may therefore be in the protein part of the antigen. The purified 45 kD antigen displayed protease activity at alkaline pH. It was inhibited by PMSF and ethylene diamine tetraacetic acid (EDTA). Proteolytic activity of the antigen may contribute significantly to pathogenesis by destroying the elastin present in the lung tissue.

Aspergillus fumigatus Specific Antibodies in Multitransfused Children with Human Immunodeficiency Virus (HIV) Infection in Relation to Serum Levels of Interleukin-2, Gamma Interferon and Tumour Necrosis Factor

Anti-Aspergillus fumigatus antibodies (IgG and IgE class) and serum levels of cytokines (gamma Interferon, Interleukin-2 and tumour necrosis factor-alpha) were studied in multitransfused (MT) children in relation to human immunodeficiency virus (HIV) infection. The specific antibodies to Aspergillus fumigatus were present in 25 per cent of MT children seropositive for HIV as compared to only 2 per cent among HIV-negative MT children (X2 = 14, P < 0.001). Estimation of serum cytokines level in MT children showed that the asymptomatic HIV-infected children had elevated levels of gamma interferon (Y-IFN) and tumor necrosis factor-alpha (TNF-alpha) without any alteration of Interleukin-2 (IL-2) level, compared to HIV-negative group. However, clinically diagnosed cases of AIDS in the HIV-infected group showed elevation of all the three cytokines levels as compared to HIV negative group, as well as asymptomatic HIV infected group. Presence or absence of concomitant A. fumigatus infection did not lead to alteration of Y-IFN and IL-2 level in the HIV infected group, while TNF-alpha levels were markedly raised in the cases with evidences of presence of A. fumigatus specific antibodies irrespective of whether the group belonged to asymptomatic HIV infection or clinically proven cases of AIDS. The significance of these altered cytokines profile with respect to occurence of A. fumigatus infection in HIV-positive MT children has been discussed.