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Genetic Diversity in the Himalayan Populations of Nepal and Tibet Tenzin Gayden Florida International University, [email protected]

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Genetic Diversity in the Himalayan Populations of Nepal and Tibet Tenzin Gayden Florida International University, Tgayd001@Fiu.Edu Florida International University FIU Digital Commons FIU Electronic Theses and Dissertations University Graduate School 3-19-2012 Genetic Diversity in the Himalayan Populations of Nepal and Tibet Tenzin Gayden Florida International University, [email protected] DOI: 10.25148/etd.FI12042312 Follow this and additional works at: https://digitalcommons.fiu.edu/etd Recommended Citation Gayden, Tenzin, "Genetic Diversity in the Himalayan Populations of Nepal and Tibet" (2012). FIU Electronic Theses and Dissertations. 580. https://digitalcommons.fiu.edu/etd/580 This work is brought to you for free and open access by the University Graduate School at FIU Digital Commons. It has been accepted for inclusion in FIU Electronic Theses and Dissertations by an authorized administrator of FIU Digital Commons. For more information, please contact [email protected]. FLORIDA INTERNATIONAL UNIVERSITY Miami, Florida GENETIC DIVERSITY IN THE HIMALAYAN POPULATIONS OF NEPAL AND TIBET A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in BIOLOGY by Tenzin Gayden 2012 To: Dean Kenneth G. Furton College of Arts and Sciences This dissertation, written by Tenzin Gayden, and entitled Genetic Diversity in the Himalayan Populations of Nepal and Tibet, having been approved in respect to style and intellectual content, is referred to you for judgment. We have read this dissertation and recommend that it be approved. ______________________________________ Timothy M. Collins ______________________________________ Bruce R. McCord ______________________________________ DeEtta K. Mills ______________________________________ George T. Duncan ______________________________________ Rene J. Herrera, Major Professor Date of Defense: March 19, 2012 The dissertation of Tenzin Gayden is approved. ______________________________________ Dean Kenneth G. Furton College of Arts and Sciences ______________________________________ Dean Lakshmi N. Reddi University Graduate School Florida International University, 2012 ii DEDICATION Dedicated to my Grandmother, Mrs. Choekyi Dolma (1927-2012) iii ACKNOWLEDGMENTS I would like to express my sincere gratitude to my advisor, Dr. Rene J. Herrera, and the members of my committee, Dr. Timothy Collins, Dr. Bruce McCord, Dr. DeEtta Mills and Dr. George Duncan, for their constant support, patience and guidance throughout the course of my Ph.D. work. Dr. Maria Regueiro deserves my warmest thanks for her unconditional help, encouragement and advice. I want to take this opportunity to also thank all the members of Dr. Herrera's laboratory for their cooperation and support. I gratefully acknowledge the financial support I received from the University Graduate School of Florida International University: Dissertation Evidence Aquisition (Spring and Summer 2010) and Dissertation Year (2011-2012) Fellowships, which helped me to finish my doctoral research in a timely fashion. My academic journey would not have been possible without the financial help and encouragement of Mr. Maurice Gallet and Mrs. Patricia Gallet since my high school. Finally, I am indebted to my family for their patience, understanding, love and unwavering support throughout my life. iv © Copyright 2012 by Tenzin Gayden All rights reserved. The following chapters of the dissertation have already been published and are reprinted here with the kind permission of Nature Publishing Group (Chapter 2) and Springer Science and Business Media (Chapters 3 and 4) via the copyright clearance center. Chapter 2. "Genetic insights into the origins of Tibeto-Burman populations in the Himalayas", Journal of Human Genetics 54:216-223 (2009) by Gayden T, Mirabal S, Cadenas AM, Lacau H, Simms TM, Morlote D, Chennakrishnaiah S and Herrera RJ. Chapter 3. "Y-STR diversity in the Himalayas", International Journal of Legal Medicine 125:367-375 (2011) by Gayden T, Chennakrishnaiah S, La Salvia J, Jimenez S, Regueiro M, Maloney T, Persad PJ, Bukhari A, Perez A, Stojkovic O and Herrera RJ. Chapter 4. "Y-chromosomal microsatellite diversity in three culturally defined regions of the historical Tibet", Forensic Science International: Genetics (2012) (In Press) by Gayden T, Bukhari A, Chennakrishnaiah S, Stojkovic O and Herrera RJ. v ABSTRACT OF THE DISSERTATION GENETIC DIVERSITY IN THE HIMALAYAN POPULATIONS OF NEPAL AND TIBET by Tenzin Gayden Florida International University, 2012 Miami, Florida Professor Rene J. Herrera, Major Professor The Himalayan Mountain range encompasses an unparalleled landscape featuring some of the planet’s highest peaks, including Mount Everest. In the heart of this massive orographic barrier lies Nepal, sandwiched in the historically geostrategic position between the Tibetan plateau to the north and India in the south. Until recently, Nepalese and Tibetan populations remained poorly characterized genetically, partly because of their inaccessible geographical locations. In the present study, the genetic diversity of these two Himalayan populations is evaluated using different marker systems, including mitochondrial DNA (mtDNA) and Short Tandem Repeats (STRs) in the autosomes as well as on the Y-chromosome (Y-STR). While autosomal STRs are distributed throughout the genome and are biparentally inherited, the Y-chromosome and mtDNA are haploid markers and provide the paternal and maternal histories of the population, respectively. Fifteen autosomal STR loci were typed in 341 unrelated individuals from three Nepalese populations (188), namely Tamang (45), Newar (66) and Kathmandu (77), and a general collection from Tibet (153). These samples were also sequenced for the mtDNA vi control region and all of them were subsequently assigned to 75 different mtDNA haplogroups and sub-haplogroups by screening their diagnostic sites in the coding region using Restriction Fragment Length Polymorphism analysis and/or sequencing, thus achieving an unprecedented level of resolution. The results from the autosomal and mtDNA data suggest a Northeast Asian origin for the Himalayan populations, with significant genetic influence from the Indian subcontinent in Kathmandu and Newar, corroborating our previous Y-chromosome study. In contrast, Tibet displays a limited Indian component, suggesting that the Himalayan massif acted as a natural barrier for gene flow from the south. The presence of ancient Indian mtDNA lineages in Nepal implies that the region may have been inhabited by the earliest settlers who initially populated South Asia. In addition, seventeen Y-STR loci were analyzed in 350 Tibetan males from three culturally defined regions of historical Tibet: Amdo (88), Kham (109) and U-Tsang (153). The results demonstrate that the 17 Y-STR loci studied are highly polymorphic in all the three Tibetan populations examined and hence are useful for forensic cases, paternity testing and population genetic studies. vii TABLE OF CONTENTS CHAPTER PAGE I. INTRODUCTION......................................................................................................1 References ................................................................................................................6 II. GENETIC INSIGHTS INTO THE ORIGINS OF THE TIBETO-BURMAN POPULATIONS IN THE HIMALAYAS ................................................................9 A. Introduction....................................................................................................9 B. Materials and Methods.................................................................................12 C. Results ..........................................................................................................15 D. Discussion ....................................................................................................18 References ..............................................................................................................24 Appendix I .............................................................................................................29 III. Y-STR DIVERSITY IN THE HIMALAYAS.......................................................43 A. Introduction..................................................................................................43 B. Materials and Methods.................................................................................45 C. Results and Discussion.................................................................................47 References............................................................................................................53 Appendix II ............................................................................................................58 IV. Y-CHROMOSOMAL MICROSATELLITE DIVERSITY IN THREE CULTURALLY DEFINED REGIONS OF HISTORIC TIBET...........................77 A. Introduction..................................................................................................77 B. Materials and Methods.................................................................................79 C. Results and Discussion.................................................................................82 D. Conclusion ...................................................................................................85 References...........................................................................................................86 Appendix III...........................................................................................................92 V. MITOCHRONDRIAL GENOME VARIATION IN NEPALESE AND TIBETAN
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