Indian genetic disease database

Sanchari Pradhan 1 Mainak Sengupta 0 Anirban Dutta 1 Kausik Bhattacharyya 0 Sumit K. Bag 1 Chitra Dutta 1 Kunal Ray 0 0 Molecular and Human Genetics Division, Indian Institute of Chemical Biology (a unit of CSIR) , Kolkata, India 1 Structural Biology and Bioinformatics Division Indians, representing about one-sixth of the world population, consist of several thousands of endogamous groups with strong potential for excess of recessive diseases. However, no database is available on Indian population with comprehensive information on the diseases common in the country. To address this issue, we present Indian Genetic Disease Database (IGDD) release 1.0 (http://www .igdd.iicb.res.in)an integrated and curated repository of growing number of mutation data on common genetic diseases afflicting the Indian populations. Currently the database covers 52 diseases with information on 5760 individuals carrying the mutant alleles of causal genes. Information on locus heterogeneity, type of mutation, clinical and biochemical data, geographical location and common mutations are furnished based on published literature. The database is currently designed to work best with Internet Explorer 8 (optimal resolution 1440 900) and it can be searched based on disease of interest, causal gene, type of mutation and geographical location of the patients or carriers. Provisions have been made for deposition of new data and logistics for regular updation of the database. The IGDD web portal, planned to be made freely available, contains user-friendly interfaces and is expected to be highly useful to the geneticists, clinicians, biologists and patient support groups of various genetic diseases. - The load of genetic diseases varies widely between different populations depending on its structure, reproductive practices and other factors. Control and management of the genetic disorders depend on identification of the variants in the genome that are causally linked with the disease. The spectrum of such variants, i.e. mutations, is different in different population groups. Remarkable progress has been made towards capturing the genomic variation in the context of genetic diseases with the advancement of DNA sequencing technologies, the capacity to handle large amount of data by building databases and faster dissemination of information through the worldwide web. It is, therefore, not surprising that the initial modest beginning of Mendelian Inheritance of Man (MIM) transformed later to Online MIM (OMIM). Currently, the most expanded version of database specifically cataloging the mutations relating genetic diseases across globe is Human Gene Mutation Database (HGMD). In addition, special interest groups generated locus specific databases (LSDBs) and lately national and ethnic mutation databases (NEMDBs) have also emerged containing mutational data for specific countries (Table 1). Such endeavor enormously boosts the efforts related to diagnosis of genetic diseases, detection of carriers for disease management and control and genetic counseling to mitigate the suffering of the affected families. However, no such database on genetic diseases exists for India, a country inhabited by more than a billion people and predicted to have a high load of recessive disorders in the population. The evolutionary history of primitive Indian ethnic groups and migration from Africa, middle-east and west Asia, southern China and south-east Asia has added to the genetic diversity of the country (9). However, religion, language and geographical location of habitat serve as barriers to random mating in the Indian population. Inbreeding is practiced in some geographical regions of India (population-inbreeding coefficient: 0.00 to 0.20) (10). Thus, the overall heterogeneity of population along with the underlying endogamy makes India, a unique case of importance with respect to a high prevalence of genetic diseases and mutations. This highlights the importance of identifying recessive diseases in the Indian groups and screening the causal genes. In addition to the overall effect of founder events, in some communities, the load of genetic disorder is relatively higher due to the practice of consanguineous marriage, especially in south India (11). In March 2006, a study conducted through the March of Dimes Birth Defect Foundation, reported the birth defect prevalence in India as 64.4 (per 1000 live births) (12). Rao and Ghosh (2005) report that 1 out of 20 children admitted to hospital has a genetic disorder that ultimately account for about 1 out of 10 childhood deaths (13). In Indias urban areas, congenital malformations and genetic disorders are the third most common cause of mortality in newborns (14). However, there is no common source of information to assess the load of specific genetic diseases reported in India, extent of locus and mutational heterogeneity, common mutations in the causal genes and the extent of molecular studies carried out vis-a` -vis lack of it in the context of the disease load. In fact, most of the pilot studies are local and hospital based. The genetic services are also not well established and localized sporadically. The situation certainly calls for a comprehensive repository of mutational data aided by specific clinical and other relevant information of patients from different regions of India. Here we describe Indian Genetic Disease Database (IGDD), a comprehensive documentation that intends to record patient-specific mutation spectrum of genetic diseases among the Indian population that would help designing assays and diagnostic tests to detect mutations, diagnose genetic diseases and identify carriers. DATABASE ORGANIZATION The logistics based on which IGDD has been created is shown schematically in Figure 1. The database offers an integrated and curated repository of experimentally characterized and reported mutations responsible for genetic disorders in Indian population. An easy-to-use web interface allows a remote user to retrieve (and submit) data through interactive web forms. The home page of IGDD provides links to other major publicdomain knowledge-bases on human genetic disorders. Details of the software design, data sources, query options and other features of the database are described in the following subsections. Software design and implementation The database is designed and implemented on a three-tier architectureuser/client, web-interface and RDBMS backend. The web interface is comprised of a collection of web applications/web forms developed in Microsoft Visual Basic .NET 2003. The home page of the database (http://www.igdd.iicb.res.in) serves as the gateway to the interlinked web forms capable of querying the database contents dynamically as instructed (by the user) through button clicks, check-boxes and drop-down menus. In the backend, the relational database is managed with ORACLE 9i. The data collected from different sources are initially stored in manually curat (...truncated)