Bio

Professional Education


  • Doctor of Philosophy, University of Arizona (2012)
  • Licenciado, Universidad Nacional De Cuyo (2000)

Stanford Advisors


Publications

All Publications


  • The Divergence of Neandertal and Modern Human Y Chromosomes. American journal of human genetics Mendez, F. L., Poznik, G. D., Castellano, S., Bustamante, C. D. 2016; 98 (4): 728-734

    Abstract

    Sequencing the genomes of extinct hominids has reshaped our understanding of modern human origins. Here, we analyze ∼120 kb of exome-captured Y-chromosome DNA from a Neandertal individual from El Sidrón, Spain. We investigate its divergence from orthologous chimpanzee and modern human sequences and find strong support for a model that places the Neandertal lineage as an outgroup to modern human Y chromosomes-including A00, the highly divergent basal haplogroup. We estimate that the time to the most recent common ancestor (TMRCA) of Neandertal and modern human Y chromosomes is ∼588 thousand years ago (kya) (95% confidence interval [CI]: 447-806 kya). This is ∼2.1 (95% CI: 1.7-2.9) times longer than the TMRCA of A00 and other extant modern human Y-chromosome lineages. This estimate suggests that the Y-chromosome divergence mirrors the population divergence of Neandertals and modern human ancestors, and it refutes alternative scenarios of a relatively recent or super-archaic origin of Neandertal Y chromosomes. The fact that the Neandertal Y we describe has never been observed in modern humans suggests that the lineage is most likely extinct. We identify protein-coding differences between Neandertal and modern human Y chromosomes, including potentially damaging changes to PCDH11Y, TMSB4Y, USP9Y, and KDM5D. Three of these changes are missense mutations in genes that produce male-specific minor histocompatibility (H-Y) antigens. Antigens derived from KDM5D, for example, are thought to elicit a maternal immune response during gestation. It is possible that incompatibilities at one or more of these genes played a role in the reproductive isolation of the two groups.

    View details for DOI 10.1016/j.ajhg.2016.02.023

    View details for PubMedID 27058445

  • A global reference for human genetic variation NATURE Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., Clark, A. G., Donnelly, P., Eichler, E. E., Flicek, P., Gabriel, S. B., Gibbs, R. A., Green, E. D., Hurles, M. E., Knoppers, B. M., Korbel, J. O., Lander, E. S., Lee, C., Lehrach, H., Mardis, E. R., Marth, G. T., McVean, G. A., Nickerson, D. A., Schmidt, J. P., Sherry, S. T., Wang, J., Wilson, R. K., Gibbs, R. A., Boerwinkle, E., Doddapaneni, H., Han, Y., Korchina, V., Kovar, C., Lee, S., Muzny, D., Reid, J. G., Zhu, Y., Wang, J., Chang, Y., Feng, Q., Fang, X., Guo, X., Jian, M., Jiang, H., Jin, X., Lan, T., Li, G., Li, J., Li, Y., Liu, S., Liu, X., Lu, Y., Ma, X., Tang, M., Wang, B., Wang, G., Wu, H., Wu, R., Xu, X., Yin, Y., Zhang, D., Zhang, W., Zhao, J., Zhao, M., Zheng, X., Lander, E. S., Altshuler, D. M., Gabriel, S. B., Gupta, N., Gharani, N., Toji, L. H., Gerry, N. P., Resch, A. M., Flicek, P., Barker, J., Clarke, L., Gil, L., Hunt, S. E., Kelman, G., Kulesha, E., Leinonen, R., McLaren, W. M., Radhakrishnan, R., Roa, A., Smirnov, D., Smith, R. E., Streeter, I., Thormann, A., Toneva, I., Vaughan, B., Zheng-Bradley, X., Bentley, D. R., Grocock, R., Humphray, S., James, T., Kingsbury, Z., Lehrach, H., Sudbrak, R., Albrecht, M. W., Amstislavskiy, V. S., Borodina, T. A., Lienhard, M., Mertes, F., Sultan, M., Timmermann, B., Yaspo, M., Mardis, E. R., Wilson, R. K., Fulton, L., Fulton, R., Sherry, S. T., Ananiev, V., Belaia, Z., Beloslyudtsev, D., Bouk, N., Chen, C., Church, D., Cohen, R., Cook, C., Garner, J., Hefferon, T., Kimelman, M., Liu, C., Lopez, J., Meric, P., O'Sullivan, C., Ostapchuk, Y., Phan, L., Ponomarov, S., Schneider, V., Shekhtman, E., Sirotkin, K., Slotta, D., Zhang, H., McVean, G. A., Durbin, R. M., Balasubramaniam, S., Burton, J., Danecek, P., Keane, T. M., Kolb-Kokocinski, A., McCarthy, S., Stalker, J., Quail, M., Schmidt, J. P., Davies, C. J., Gollub, J., Webster, T., Wong, B., Zhan, Y., Auton, A., Campbell, C. L., Kong, Y., Marcketta, A., Gibbs, R. A., Yu, F., Antunes, L., Bainbridge, M., Muzny, D., Sabo, A., Huang, Z., Wang, J., Coin, L. J., Fang, L., Guo, X., Jin, X., Li, G., Li, Q., Li, Y., Li, Z., Lin, H., Liu, B., Luo, R., Shao, H., Xie, Y., Ye, C., Yu, C., Zhang, F., Zheng, H., Zhu, H., Alkan, C., Dal, E., Kahveci, F., Marth, G. T., Garrison, E. P., Kural, D., Lee, W., Leong, W. F., Stromberg, M., Ward, A. N., Wu, J., Zhang, M., Daly, M. J., DePristo, M. A., Handsaker, R. E., Altshuler, D. M., Banks, E., Bhatia, G., del Angel, G., Gabriel, S. B., Genovese, G., Gupta, N., Li, H., Kashin, S., Lander, E. S., McCarroll, S. A., Nemesh, J. C., Poplin, R. E., Yoon, S. C., Lihm, J., Makarov, V., Clark, A. G., Gottipati, S., Keinan, A., Rodriguez-Flores, J. L., Korbel, J. O., Rausch, T., Fritz, M. H., Stuetz, A. M., Flicek, P., Beal, K., Clarke, L., Datta, A., Herrero, J., McLaren, W. M., Ritchie, G. R., Smith, R. E., Zerbino, D., Zheng-Bradley, X., Sabeti, P. C., Shlyakhter, I., Schaffner, S. F., Vitti, J., Cooper, D. N., Ball, E. V., Stenson, P. D., Bentley, D. R., Barnes, B., Bauer, M., Cheetham, R. K., Cox, A., Eberle, M., Humphray, S., Kahn, S., Murray, L., Peden, J., Shaw, R., Kenny, E. E., Batzer, M. A., Konkel, M. K., Walker, J. A., MacArthur, D. G., Lek, M., Sudbrak, R., Amstislavskiy, V. S., Herwig, R., Mardis, E. R., Ding, L., Koboldt, D. C., Larson, D., Ye, K., Gravel, S., Swaroop, A., Chew, E., Lappalainen, T., Erlich, Y., Gymrek, M., Willems, T. F., Simpson, J. T., Shriver, M. D., Rosenfeld, J. A., Bustamante, C. D., Montgomery, S. B., De La Vega, F. M., Byrnes, J. K., Carroll, A. W., DeGorter, M. K., Lacroute, P., Maples, B. K., Martin, A. R., Moreno-Estrada, A., Shringarpure, S. S., Zakharia, F., Halperin, E., Baran, Y., Lee, C., Cerveira, E., Hwang, J., Malhotra, A., Plewczynski, D., Radew, K., Romanovitch, M., Zhang, C., Hyland, F. C., Craig, D. W., Christoforides, A., Homer, N., Izatt, T., Kurdoglu, A. A., Sinari, S. A., Squire, K., Sherry, S. T., Xiao, C., Sebat, J., Antaki, D., Gujral, M., Noor, A., Ye, K., Burchard, E. G., Hernandez, R. D., Gignoux, C. R., Haussler, D., Katzman, S. J., Kent, W. J., Howie, B., Ruiz-Linares, A., Dermitzakis, E. T., Devine, S. E., Goncalo, R. A., Kang, H. M., Kidd, J. M., Blackwell, T., Caron, S., Chen, W., Emery, S., Fritsche, L., Fuchsberger, C., Jun, G., Li, B., Lyons, R., Scheller, C., Sidore, C., Song, S., Sliwerska, E., Taliun, D., Tan, A., Welch, R., Wing, M. K., Zhan, X., Awadalla, P., Hodgkinson, A., Li, Y., Shi, X., Quitadamo, A., Lunter, G., McVean, G. A., Marchini, J. L., Myers, S., Churchhouse, C., Delaneau, O., Gupta-Hinch, A., Kretzschmar, W., Iqbal, Z., Mathieson, I., Menelaou, A., Rimmer, A., Xifara, D. K., Oleksyk, T. K., Fu, Y., Liu, X., Xiong, M., Jorde, L., Witherspoon, D., Xing, J., Eichler, E. E., Browning, B. L., Browning, S. R., Hormozdiari, F., Sudmant, P. H., Khurana, E., Durbin, R. M., Hurles, M. E., Tyler-Smith, C., Albers, C. A., Ayub, Q., Balasubramaniam, S., Chen, Y., Colonna, V., Danecek, P., Jostins, L., Keane, T. M., McCarthy, S., Walter, K., Xue, Y., Gerstein, M. B., Abyzov, A., Balasubramanian, S., Chen, J., Clarke, D., Fu, Y., Harmanci, A. O., Jin, M., Lee, D., Liu, J., Mu, X. J., Zhang, J., Zhang, Y., Li, Y., Luo, R., Zhu, H., Alkan, C., Dal, E., Kahveci, F., Marth, G. T., Garrison, E. P., Kural, D., Lee, W., Ward, A. N., Wu, J., Zhang, M., McCarroll, S. A., Handsaker, R. E., Altshuler, D. M., Banks, E., del Angel, G., Genovese, G., Hartl, C., Li, H., Kashin, S., Nemesh, J. C., Shakir, K., Yoon, S. C., Lihm, J., Makarov, V., Degenhardt, J., Korbel, J. O., Fritz, M. H., Meiers, S., Raeder, B., Rausch, T., Stuetz, A. M., Flicek, P., Casale, F. P., Clarke, L., Smith, R. E., Stegle, O., Zheng-Bradley, X., Bentley, D. R., Barnes, B., Cheetham, R. K., Eberle, M., Humphray, S., Kahn, S., Murray, L., Shaw, R., Lameijer, E., Batzer, M. A., Konkel, M. K., Walker, J. A., Ding, L., Hall, I., Ye, K., Lacroute, P., Lee, C., Cerveira, E., Malhotra, A., Hwang, J., Plewczynski, D., Radew, K., Romanovitch, M., Zhang, C., Craig, D. W., Homer, N., Church, D., Xiao, C., Sebat, J., Antaki, D., Bafna, V., Michaelson, J., Ye, K., Devine, S. E., Gardner, E. J., Abecasis, G. R., Kidd, J. M., Mills, R. E., Dayama, G., Emery, S., Jun, G., Shi, X., Quitadamo, A., Lunter, G., McVean, G. A., Chen, K., Fan, X., Chong, Z., Chen, T., Witherspoon, D., Xing, J., Eichler, E. E., Chaisson, M. J., Hormozdiari, F., Huddleston, J., Malig, M., Nelson, B. J., Sudmant, P. H., Parrish, N. F., Khurana, E., Hurles, M. E., Blackburne, B., Lindsay, S. J., Ning, Z., Walter, K., Zhang, Y., Gerstein, M. B., Abyzov, A., Chen, J., Clarke, D., Lam, H., Mu, X. J., Sisu, C., Zhang, J., Zhang, Y., Gibbs, R. A., Yu, F., Bainbridge, M., Challis, D., Evani, U. S., Kovar, C., Lu, J., Muzny, D., Nagaswamy, U., Reid, J. G., Sabo, A., Yu, J., Guo, X., Li, W., Li, Y., Wu, R., Marth, G. T., Garrison, E. P., Leong, W. F., Ward, A. N., del Angel, G., DePristo, M. A., Gabriel, S. B., Gupta, N., Hartl, C., Poplin, R. E., Clark, A. G., Rodriguez-Flores, J. L., Flicek, P., Clarke, L., Smith, R. E., Zheng-Bradley, X., MacArthur, D. G., Mardis, E. R., Fulton, R., Koboldt, D. C., Gravel, S., Bustamante, C. D., Craig, D. W., Christoforides, A., Homer, N., Izatt, T., Sherry, S. T., Xiao, C., Dermitzakis, E. T., Abecasis, G. R., Kang, H. M., McVean, G. A., Gerstein, M. B., Balasubramanian, S., Habegger, L., Yu, H., Flicek, P., Clarke, L., Cunningham, F., Dunham, I., Zerbino, D., Zheng-Bradley, X., Lage, K., Jespersen, J. B., Horn, H., Montgomery, S. B., DeGorter, M. K., Khurana, E., Tyler-Smith, C., Chen, Y., Colonna, V., Xue, Y., Gerstein, M. B., Balasubramanian, S., Fu, Y., Kim, D., Auton, A., Marcketta, A., DeSalle, R., Narechania, A., Sayres, M. A., Garrison, E. P., Handsaker, R. E., Kashin, S., McCarroll, S. A., Rodriguez-Flores, J. L., Flicek, P., Clarke, L., Zheng-Bradley, X., Erlich, Y., Gymrek, M., Willems, T. F., Bustamante, C. D., Mendez, F. L., Poznik, G. D., Underhill, P. A., Lee, C., Cerveira, E., Malhotra, A., Romanovitch, M., Zhang, C., Abecasis, G. R., Coin, L., Shao, H., Mittelman, D., Tyler-Smith, C., Ayub, Q., Banerjee, R., Cerezo, M., Chen, Y., Fitzgerald, T., Louzada, S., Massaia, A., McCarthy, S., Ritchie, G. R., Xue, Y., Yang, F., Gibbs, R. A., Kovar, C., Kalra, D., Hale, W., Muzny, D., Reid, J. G., Wang, J., Dan, X., Guo, X., Li, G., Li, Y., Ye, C., Zheng, X., Altshuler, D. M., Flicek, P., Clarke, L., Zheng-Bradley, X., Bentley, D. R., Cox, A., Humphray, S., Kahn, S., Sudbrak, R., Albrecht, M. W., Lienhard, M., Larson, D., Craig, D. W., Izatt, T., Kurdoglu, A. A., Sherry, S. T., Xiao, C., Haussler, D., Abecasis, G. R., McVean, G. A., Durbin, R. M., Balasubramaniam, S., Keane, T. M., McCarthy, S., Stalker, J., Chakravarti, A., Knoppers, B. M., Abecasis, G. R., Barnes, K. C., Beiswanger, C., Burchard, E. G., Bustamante, C. D., Cai, H., Cao, H., Durbin, R. M., Gerry, N. P., Gharani, N., Gibbs, R. A., Gignoux, C. R., Gravel, S., Henn, B., Jones, D., Jorde, L., Kaye, J. S., Keinan, A., Kent, A., Kerasidou, A., Li, Y., Mathias, R., McVean, G. A., Moreno-Estrada, A., Ossorio, P. N., Parker, M., Resch, A. M., Rotimi, C. N., Royal, C. D., Sandoval, K., Su, Y., Sudbrak, R., Tian, Z., Tishkoff, S., Toji, L. H., Tyler-Smith, C., Via, M., Wang, Y., Yang, H., Yang, L., Zhu, J., Bodmer, W., Bedoya, G., Ruiz-Linares, A., Cai, Z., Gao, Y., Chu, J., Peltonen, L., Garcia-Montero, A., Orfao, A., Dutil, J., Martinez-Cruzado, J. C., Oleksyk, T. K., Barnes, K. C., Mathias, R. A., Hennis, A., Watson, H., McKenzie, C., Qadri, F., LaRocque, R., Sabeti, P. C., Zhu, J., Deng, X., Sabeti, P. C., Asogun, D., Folarin, O., Happi, C., Omoniwa, O., Stremlau, M., Tariyal, R., Jallow, M., Joof, F. S., Corrah, T., Rockett, K., Kwiatkowski, D., Kooner, J., Tran Tinh Hien, T. T., Dunstan, S. J., Nguyen Thuy Hang, N. T., Fonnie, R., Garry, R., Kanneh, L., Moses, L., Sabeti, P. C., Schieffelin, J., Grant, D. S., Gallo, C., Poletti, G., Saleheen, D., Rasheed, A., Brook, L. D., Felsenfeld, A., McEwen, J. E., Vaydylevich, Y., Green, E. D., Duncanson, A., Dunn, M., Schloss, J. A., Wang, J., Yang, H., Auton, A., Brooks, L. D., Durbin, R. M., Garrison, E. P., Kang, H. M., Korbel, J. O., Marchini, J. L., McCarthy, S., McVean, G. A., Abecasis, G. R. 2015; 526 (7571): 68-?
  • Reply to 'The 'extremely ancient' chromosome that isn't' by Elhaik et al. European journal of human genetics Mendez, F. L., Veeramah, K. R., Thomas, M. G., Karafet, T. M., Hammer, M. F. 2015; 23 (5): 564-567

    View details for DOI 10.1038/ejhg.2014.148

    View details for PubMedID 25315660

  • A recent bottleneck of Y chromosome diversity coincides with a global change in culture GENOME RESEARCH Karmin, M., Saag, L., Vicente, M., Sayres, M. A., Jarve, M., Talas, U. G., Rootsi, S., Ilumaee, A., Maegi, R., Mitt, M., Pagani, L., Puurand, T., Faltyskova, Z., Clemente, F., Cardona, A., Metspalu, E., Sahakyan, H., Yunusbayev, B., Hudjashov, G., DeGiorgio, M., Loogvaeli, E., Eichstaedt, C., Eelmets, M., Chaubey, G., Tambets, K., Litvinov, S., Mormina, M., Xue, Y., Ayub, Q., Zoraqi, G., Korneliussen, T. S., Akhatova, F., Lachance, J., Tishkoff, S., Momynaliev, K., Ricaut, F., Kusuma, P., Razafindrazaka, H., Pierron, D., Cox, M. P., Nurun, G., Sultana, N., Willerslev, R., Muller, C., Westaway, M., Lambert, D., Skaro, V., Kovacevic, L., Turdikulova, S., Dalimova, D., Khusainova, R., Trofimova, N., Akhmetova, V., Khidiyatova, I., Lichman, D. V., Isakova, J., Pocheshkhova, E., Sabitov, Z., Barashkov, N. A., Nymadawa, P., Mihailov, E., Seng, J. W., Evseeva, I., Migliano, A. B., Abdullah, S., Andriadze, G., Primorac, D., Atramentova, L., Utevska, O., Yepiskoposyan, L., Marjanovic, D., Kushniarevich, A., Behar, D. M., Gilissen, C., Vissers, L., Veltman, J. A., Balanovska, E., Derenko, M., Malyarchuk, B., Metspalu, A., Fedorova, S., Eriksson, A., Manica, A., Mendez, F. L., Karafet, T. M., Veeramah, K. R., Bradman, N., Hammer, M. F., Osipova, L. P., Balanovsky, O., Khusnutdinova, E. K., Johnsen, K., Remm, M., Thomas, M. G., Tyler-Smith, C., Underhill, P. A., Willerslev, E., Nielsen, R., Metspalu, M., Villems, R., Kivisild, T. 2015; 25 (4): 459-466

    Abstract

    It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.

    View details for DOI 10.1101/gr.186684.114

    View details for Web of Science ID 000352139200001

    View details for PubMedID 25770088

  • Gibbon genome and the fast karyotype evolution of small apes. Nature Carbone, L., Harris, R. A., Gnerre, S., Veeramah, K. R., Lorente-Galdos, B., Huddleston, J., Meyer, T. J., Herrero, J., Roos, C., Aken, B., Anaclerio, F., Archidiacono, N., Baker, C., Barrell, D., Batzer, M. A., Beal, K., Blancher, A., Bohrson, C. L., Brameier, M., Campbell, M. S., Capozzi, O., Casola, C., Chiatante, G., Cree, A., Damert, A., de Jong, P. J., Dumas, L., Fernandez-Callejo, M., Flicek, P., Fuchs, N. V., Gut, I., Gut, M., Hahn, M. W., Hernandez-Rodriguez, J., Hillier, L. W., Hubley, R., Ianc, B., Izsvák, Z., Jablonski, N. G., Johnstone, L. M., Karimpour-Fard, A., Konkel, M. K., Kostka, D., Lazar, N. H., Lee, S. L., Lewis, L. R., Liu, Y., Locke, D. P., Mallick, S., Mendez, F. L., Muffato, M., Nazareth, L. V., Nevonen, K. A., O'Bleness, M., Ochis, C., Odom, D. T., Pollard, K. S., Quilez, J., Reich, D., Rocchi, M., Schumann, G. G., Searle, S., Sikela, J. M., Skollar, G., Smit, A., Sonmez, K., ten Hallers, B., Terhune, E., Thomas, G. W., Ullmer, B., Ventura, M., Walker, J. A., Wall, J. D., Walter, L., Ward, M. C., Wheelan, S. J., Whelan, C. W., White, S., Wilhelm, L. J., Woerner, A. E., Yandell, M., Zhu, B., Hammer, M. F., Marques-Bonet, T., Eichler, E. E., Fulton, L., Fronick, C., Muzny, D. M., Warren, W. C., Worley, K. C., Rogers, J., Wilson, R. K., Gibbs, R. A. 2014; 513 (7517): 195-201

    Abstract

    Gibbons are small arboreal apes that display an accelerated rate of evolutionary chromosomal rearrangement and occupy a key node in the primate phylogeny between Old World monkeys and great apes. Here we present the assembly and analysis of a northern white-cheeked gibbon (Nomascus leucogenys) genome. We describe the propensity for a gibbon-specific retrotransposon (LAVA) to insert into chromosome segregation genes and alter transcription by providing a premature termination site, suggesting a possible molecular mechanism for the genome plasticity of the gibbon lineage. We further show that the gibbon genera (Nomascus, Hylobates, Hoolock and Symphalangus) experienced a near-instantaneous radiation ∼5 million years ago, coincident with major geographical changes in southeast Asia that caused cycles of habitat compression and expansion. Finally, we identify signatures of positive selection in genes important for forelimb development (TBX5) and connective tissues (COL1A1) that may have been involved in the adaptation of gibbons to their arboreal habitat.

    View details for DOI 10.1038/nature13679

    View details for PubMedID 25209798

  • New binary polymorphisms reshape and increase resolution of the human Y chromosomal haplogroup tree GENOME RESEARCH Karafet, T. M., Mendez, F. L., Meilerman, M. B., Underhill, P. A., Zegura, S. L., Hammer, M. F. 2008; 18 (5): 830-838

    Abstract

    Markers on the non-recombining portion of the human Y chromosome continue to have applications in many fields including evolutionary biology, forensics, medical genetics, and genealogical reconstruction. In 2002, the Y Chromosome Consortium published a single parsimony tree showing the relationships among 153 haplogroups based on 243 binary markers and devised a standardized nomenclature system to name lineages nested within this tree. Here we present an extensively revised Y chromosome tree containing 311 distinct haplogroups, including two new major haplogroups (S and T), and incorporating approximately 600 binary markers. We describe major changes in the topology of the parsimony tree and provide names for new and rearranged lineages within the tree following the rules presented by the Y Chromosome Consortium in 2002. Several changes in the tree topology have important implications for studies of human ancestry. We also present demography-independent age estimates for 11 of the major clades in the new Y chromosome tree.

    View details for DOI 10.1101/gr.7172008

    View details for Web of Science ID 000255504600015

    View details for PubMedID 18385274