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Dr Lalji Singh Director, CCMB Hyderabad, India 4,635 Well Defined Pppopulations in India 532 Tribes (7.76%) 72 Primitive Tribes, (36 Hunters and Gatherers)

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Dr Lalji Singh Director, CCMB Hyderabad, India 4,635 Well Defined Pppopulations in India 532 Tribes (7.76%) 72 Primitive Tribes, (36 Hunters and Gatherers) Dr Lalji Singh Director, CCMB Hyderabad, India 4,635 well defined pppopulations in India 532 tribes (7.76%) 72 primitive tribes, (36 hunters and gatherers) Diversities in: language social structure dress and food habit marriage practices physical appearance genetic architecture Indian population structure ¾ Mos t unique ftfeature is the diiidivision of popultilation itinto stitltrictly defined hierarchical endogamous castes, tribes and religious ggproups. ¾ Boundaries of these subdivisions are highly impermeable. ¾ In practice, although not in theory, the religious groups like Muslims, Christians, Sikhs and others recognize endogamy rules. ¾ The above features, by and large, apply to each linguistic region of the country. ¾ Language forms strong barriers for gene flow between such regions, even among the castes, tribes or religious groups of similar or same hierarchy.e.g. Brahmins of A.P. and U.P. The first out of Africa human From the unforgiving cold of the Arctic tundra to the blaz ing heat of the Aus tra lian out bac k and the humid forests of the Amazon, our own species Homo sapiens penetrated every corner of the gg,lobe, succeeding in an unrivalled arra y of environments. What caused them to explode out of Africa when they did? What circumstances suddenly allowed those early humans to smash down their boundaries like no species before or since? East African mega droughts between 135 and 75 thousand years ago, when the water volume of the lake Malawi was reduced by at least 95% could have been the reason for their migration out of Africa. A major rise in water levels and shift to more humid and decreased environmental variability conditions over much tropical after ~70 Kyr ago may have stimulated the expansion and migrations of early modern human populations. Scholz et al. PNAS 104, 16416-16421, October 2007 Algeria Romania >35K ~40K Israel 120-90K Portugal ~25K China ~40K Northern Route Andaman and Nicobar Islanders short stature features with dark skin Negritos Mongoloid Chinese peppercorn hair Malays scant body hair Burmese Great Andamanese Little Andamanese Nicobarese Shompen Cari Kora Onge Bo Jeru Kede Jarawa Kol Juwoi Pucikwar Bale Ben Sentinelese Andaman and 572 Islands Nico bar I s lan ds Jarawa Gr. Andamanese Sentenelese Onge Nicobarese Onge 98 Shompens 180 Jarawa 200 Nicobarese 22,000 StSentene lese 250 Gr. Anda. 36 Shompen Genetic affinities among the tribal populations of Andaman and Nicobar Islands Onge Gr. Andamanese Jarawa Nico barese Shompen Great Andamanese & Onge settled, and receive food rations and other aid from the Indian Government. The cult ure, l anguages and ori gi n of th e Andamanese have been the subject of speculation for centuries . Blood group and protein studies suggest that the Andamanese are more closely related to Oceanic people. Our study is the first molecular data on these enigmatic tribes to understand their origin, evolution and migration. Y-SNP based maximum parsimony phylogeny of Andamanese Onge Curr. Biol. (2003) Jarawa GA Nico GA GA GA Complete mtDNA sequence analysis of … Nicobarese 5 Onge 5 Great Andamanese 5 Nicobarese Onge/ Gr. Andamanese Africa tt GG India East Asia PN Eas Identified several novel mutations, which are not found anywhere in the world, including our survey of 6,500 Indians L3 Andamanese are the descendants of the first modern human migrated out of Africa through Southern Coastal rout via India about 65,000 – 70,000 years ago. Whereas the Nicobarese are the recent migrants from the Southeast Asia about 18,000 years ago. Migration of Andamanese India Africa A & N ilislan ds Migration of Andamanese India Africa A & N ilislan ds Sc ience (2005) Algeria Romania >35K ~40K Israel 120-90K Portugal ~25K China ~40K Southern Route 65K Andaman & Nicobar Islands 70 – 65 K Archaeological and genetic evidence point to a single successful dispersal across Southern and Southeastern Asia into Australia and with only a secondary and later dispersal into Europe. “From the site of Patric in Western India, Jwalapuram in Southern India, and Batadomba-Lena in Sri Lanka, these are archaeological assemblages showing some striking resemblances to those from Eastern and Southern Africa that must be from very close to the period when modern humans first dispersed from Africa. These point strongly to a direct connection between the earliest modern human colonists in Southern Asia and their probable ancestors in Eastern and Southern Africa ” Neanderthals were the victims of early genocide by modern humans a consequence of our inherently violent nature. Paul Mellars, Science (2006) 313, 796-800 An Asian perspective on early human dispersa l from Afri ca “Asia’s earliest hominids presence has been extended up to 1.8 Myrs ago, hundred of thousands of years earlier than previously envisaged . It i s ti me t o d evel op alt ernati ves t o one of palaeoanthropology’s most basic paradigms: ‘out of Africa ’”. Absence of evidence is not evidence of absence. Dennell and Rochrocky, Nature 438: 1101-1104 (2005) ElEarly man b ecomes earl y ape Ciochon, Nature,459: 910-911 (2009) Southern route of dispersal of modern human out of Africa: Archaeological Evidence Analysis of the archaeological assemblages at Jwalapuram in Jurreru River valley of Southern India immediately before and after the Youngest Toba Tuff (YTT) eruption recovered from archaeological industries from the site strongly suggest the presence of modern human in India at the time of the YTT eruption which occurred in Indonesia about 74,000 years ago. This was one of the earth’s largest known volcanic events (2,800 km3). The Indian subcontinent contains extensive YTT deposits. JalapramJwalapuram Petraglia et al. Science 317:114-116 (2007) Andhra Pradesh Are there any population(s) in mainland India, who are close to Andamanese? How muc h affi niti es th e I ndi an pppopulations have with Andamanese? Did the Indians contribute to the early human spread? West Bengal Kerala EtEast coast West coast Great Great Rajbanshi Andamanese Onge Andamanese Kurumba SW1 GA9 O21 O23 O19 GA8 K12 Science (()2006) GA11 O20 GA13 K17 GA15 7785 O42 K25 9617 K26 8108 10940 M31b 13710 143 8553 5.1+3.6 Ky 200 4688 M31a 16136 16519 16126 16311 9.3+4.7 Ky 15667 14407 M32a M32b 14212 12876 8092 11014 9581 16357 16294 3834 16344 16189 3337 8973 3999 16319 16183C 808 15754 16179 152 3975 2156+A 207 16124 2045 195 6366 1524 482 249d 46.3+10.9 Ky M31 16526 45.7+8.7 Ky 12189 15530 9064 15440 3817 11176 2156+A 4907 65+7 Ky 1438 M 15043 14783 10400 489 (After screening ~14,000 samples from 240 ethnic populations) Root Deep rooting lineages of Macrohaplogroup 'M' in India BMC Genomics (2006) Indian mtDNA pool consists of several deep rooting lineages of macrohaplogroup M suggesting in-situ origin of these haplogroups in South Asia, most likely in the India Deep rooting lineages of Macrohaplogroup 'M' in India Bhoi (M49) Tadvi (M33A) Oraon (M18) Khasi (M48, M50) Science (2005) BMC Genetics (2006) BMC Genomi cs (2006) Rathwa (M4A) PLoS Genetics (2006) Mahadeo Koli (M51) Pardhan (()M41) PLoS ONE (2007) Hum Hered (2008) *M34A Gr. An damanese (M31, M32) Paniyan (M3) Onge (M31, M32) 1 million SNPs (Affy array) Onge Chenchu Dravidians Australian aboriginals Austro-Asiatics Indo-Europeans Santhal Kharia Europeans Meghawal HapMap Chinese (HapMap) In collaboration with David Reich, Department of Genetics, Harvard Medical School, USA (unpublished data) Disease patt ern? Cardiomyopathies AhA he terogeneous group o fhf heart musc le diseases, leads to inadequate pumping of blood . More than 200 disease associated mutation have been reported in 20 different genes. Of which, MYBPC3 gene is involved in about 45% of the total cardiomyopathy. Deletion of 25bp Myosine Binding Protein-C3 (MYBPC3) is associated with Inheritable cardiomyypopathies in Indian patients due to skipping of wild type exon (33) Combined effect of association studies Cases Controls OR (95% CI) P n D, D D, W W, W n D, D D, W W, W Overall 5 81 714 12 687 6.99 India 800 699 0 4x10-14 (()0.6) (()10.1) (()89.2) (()1.7) (()98.3) (3.63-13.40) (n=1499) D- deleted allele; W- wild type allele Postmortem tissue Homozygous Patients dies due to heart failure Hypertrophied myofibers separated Asymmetric hypertrophy involving Dilation of the left by increased connective tissue Interventricular Septum (28 mm) and right ventricles Myofibrils consist of sarcomeres Seven major proteins Expression and localization of cMyBP-C'Ex33 proteins in Neonatal Rat Cardiomyocytes (NRCM) C-Myc a-TM M erger Control Normal Muscle Structure WT Myocardial Disarray cMyBP-C Mutant in Cardio- myocytes Recombinant adenoviruses that expressed mouse cMyBP-C'Ex33 (Mutant) were introduced into rat neonatal cardiomyocytes and immunostained with myc-tag antibodies carried only by the WT and Mutant proteins (green), and costained with D-tropomyosin (red) . Distribution of 25 bp deletion in India 6273 samples 107 ethnic populations 279 hetereozygous deletion 8 homozygous deletion 2 – 8% del eti on (4.35%) Population stratification North AP TN 50 unlinked SNP markers Anova p-value > 0.05 European HapMap Indian case/control Global distribution of 25bp deletion 2,,g085 indigenous individuals from 26 countries 25bp d el eti on was observed only in Pakistan, Sri Arose ~33,,y000 years a go Lanka, Indonesia and Malaysia Troppfpical calcific pancreatitis In Western populations, gain of function mutations in cationic trypsinogen (PRSS1) gene have been associated with Hereditary and Idiopathic chronic pancreatitis Our results suggest that rather than cationic trypsinogen gene mutations, mutations in its (i) activator Cathepsin B (CTSB) and (ii) inhibitor SPINK1 are associated with tropical calcific pancreatitis (TCP) Variations that are not associated with disease in Indians Continued… Variations that are not associated with disease in Indians Acknowledgements Indian collaborators K.
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