Medical genetics and genomic medicine in India: current status and opportunities ahead

India is the sixth largest country of the world in size and with a population 1.21 billion (http://www.censusindia.gov.in) has the distinction of being the second most populous country of the world, housing 17.5% of all humans (http://www.prb.org). It is part of the Indian subcontinent that is comprised of the surrounding countries of Pakistan, Bangladesh, Srilanka, Nepal, and China with whom it shares common cultural and anthropological roots. The southern part of India is the Indian peninsula surrounded by the Indian Ocean, the Bay of Bengal, and the Arabian Sea (Fig. 1). The Indian subcontinent has been the seat of some of the oldest civilizations of the world with the earliest historically documented remains dating back to as early as 70,000 years. This region is believed to have been initially habituated 55,000– 80,000 years back by migration from the African continent as indicated by mitochondrial and Y chromosome DNA genotypes (Majumdar 2010; Tamang et al. 2012). Subsequently, multiple events of migration and invasions from northwestern and eastern sides led to population admixture giving rise to highly heterogeneous population groups in this country. Presently, there are believed to be four main ethno-racial groupsthe Caucasoids, Australoids, Mongoloids, and Negritosin India. The Caucasoids inhabit the northern and northwestern part and speak the Indo-Aryan langauages, the Australoids the southern part and speak the Dravidian languages and the Mongoloids the northeastern part of the country and speak the Tibeto-Burman languages. The Negritos are confined to the Andaman & Nicobar islands which lie in the extreme southeastern part of the country. The majority of the modern Indian population is an admixture of two large genetically divergent and heterogeneous population groups that mixed in ancient times (about 1200– 3500 BC), known as Ancestral North Indians (ANI) or the Caucasoids and Ancestral South Indians (ASI) or the Australoids. Overall there are more than 4000 anthropologically distinct groups and 22 languages with various dialects in this diverse nation (Majumdar 2010; Narang et al. 2010; Tamang et al. 2012). Genetic studies for classifying the population into subgroups and identifying the origins have been at the best incomplete due to the vast population and extreme complexity. This poses challenges for genetics and genomic medicine research. In recent years, the Indian Genome variation consortium project has studied polymorphisms in 900 genes from 55 different population groups of India and these variations have been catalogued in the Indian Genome Variation browser. This forms an important database for design of further studies of multifactorial as well as single gene disorders (Narang et al. 2010). The geographical & linguistic disparity is further complicated by the caste system and religious boundaries, which are associated with high degree of endogamy, although recent reports have indicated some degree of admixture (Tripathi et al. 2008; Majumdar 2010; Tamang et al. 2012; Juyal et al. 2014). Consanguinity is as high as 20–30% in some specific populations, indicating the possibility of clusters of specific diseases and founder mutations (Bittles 2002; Juyal et al. 2014). Although almost all known genetic disorders