41 results on '"Sohail, Mashaal"'
Search Results
2. Mexican Biobank advances population and medical genomics of diverse ancestries
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Sohail, Mashaal, Palma-Martínez, María J., Chong, Amanda Y., Quinto-Cortés, Consuelo D., Barberena-Jonas, Carmina, Medina-Muñoz, Santiago G., Ragsdale, Aaron, Delgado-Sánchez, Guadalupe, Cruz-Hervert, Luis Pablo, Ferreyra-Reyes, Leticia, Ferreira-Guerrero, Elizabeth, Mongua-Rodríguez, Norma, Canizales-Quintero, Sergio, Jimenez-Kaufmann, Andrés, Moreno-Macías, Hortensia, Aguilar-Salinas, Carlos A., Auckland, Kathryn, Cortés, Adrián, Acuña-Alonzo, Víctor, Gignoux, Christopher R., Wojcik, Genevieve L., Ioannidis, Alexander G., Fernández-Valverde, Selene L., Hill, Adrian V. S., Tusié-Luna, María Teresa, Mentzer, Alexander J., Novembre, John, García-García, Lourdes, and Moreno-Estrada, Andrés
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- 2023
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3. Getting Genetic Ancestry Right for Science and Society
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Lewis, Anna C. F., Molina, Santiago J., Appelbaum, Paul S, Dauda, Bege, Di Rienzo, Anna, Fuentes, Agustin, Fullerton, Stephanie M., Garrison, Nanibaa' A., Ghosh, Nayanika, Hammonds, Evelynn M., Jones, David S., Kenny, Eimear E., Kraft, Peter, Lee, Sandra S. -J., Mauro, Madelyn, Novembre, John, Panofsky, Aaron, Sohail, Mashaal, Neale, Benjamin M., and Allen, Danielle S.
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Quantitative Biology - Populations and Evolution - Abstract
There is a scientific and ethical imperative to embrace a multidimensional, continuous view of ancestry and move away from continental ancestry categories
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- 2021
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4. Swapping genes within and beyond our bodies
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Sohail, Mashaal
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- 2024
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5. The Trait Specific Timing of Accelerated Genomic Change in the Human Lineage
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Kun, Eucharist, primary, Sohail, Mashaal, additional, and Narasimhan, Vagheesh, additional
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- 2024
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6. The Mexican Biobank Project promotes genetic discovery, inclusive science and local capacity building
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Sohail, Mashaal, primary and Moreno-Estrada, Andrés, additional
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- 2024
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7. Swapping genes within and beyond our bodies
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Sohail, Mashaal, primary
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- 2023
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8. Negative selection in humans and fruit flies involves synergistic epistasis
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Sohail, Mashaal, Vakhrusheva, Olga A., Sul, Jae Hoon, Pulit, Sara L., Francioli, Laurent C., van den Berg, Leonard H., Veldink, Jan H., de Bakker, Paul I. W., Bazykin, Georgii A., Kondrashov, Alexey S., and Sunyaev, Shamil R.
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- 2017
9. eLife assessment: Human-specific lncRNAs contributed critically to human evolution by distinctly regulating gene expression
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Sohail, Mashaal, primary
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- 2023
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10. The genetic architecture and evolution of the human skeletal form
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Kun, Eucharist, primary, Javan, Emily M., additional, Smith, Olivia, additional, Gulamali, Faris, additional, de la Fuente, Javier, additional, Flynn, Brianna I., additional, Vajrala, Kushal, additional, Trutner, Zoe, additional, Jayakumar, Prakash, additional, Tucker-Drob, Elliot M., additional, Sohail, Mashaal, additional, Singh, Tarjinder, additional, and Narasimhan, Vagheesh M., additional
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- 2023
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11. Ancestry: How researchers use it and what they mean by it
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Dauda, Bege, primary, Molina, Santiago J., additional, Allen, Danielle S., additional, Fuentes, Agustin, additional, Ghosh, Nayanika, additional, Mauro, Madelyn, additional, Neale, Benjamin M., additional, Panofsky, Aaron, additional, Sohail, Mashaal, additional, Zhang, Sarah R., additional, and Lewis, Anna C. F., additional
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- 2023
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12. The genetic architecture of the human skeletal form
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Kun, Eucharist, primary, Javan, Emily M., additional, Smith, Olivia, additional, Gulamali, Faris, additional, de la Fuente, Javier, additional, Flynn, Brianna I., additional, Vajrala, Kushal, additional, Trutner, Zoe, additional, Jayakumar, Prakash, additional, Tucker-Drob, Elliot M., additional, Sohail, Mashaal, additional, Singh, Tarjinder, additional, and Narasimhan, Vagheesh M., additional
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- 2023
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13. Nationwide genomic biobank in Mexico unravels demographic history and complex trait architecture from 6,057 individuals
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Sohail, Mashaal, primary, Chong, Amanda Y, additional, Quinto-Cortes, Consuelo D, additional, Palma-Martinez, Maria J, additional, Ragsdale, Aaron, additional, Medina-Munoz, Santiago G, additional, Barberena-Jonas, Carmina, additional, Delgado-Sanchez, Guadalupe, additional, Cruz-Hervert, Luis Pablo, additional, Ferreyra-Reyes, Leticia, additional, Ferreira-Guerrero, Elizabeth, additional, Mongua-Rodriguez, Norma, additional, Jimenez-Kaufmann, Andres, additional, Moreno-Macias, Hortensia, additional, Aguilar-Salinas, Carlos A, additional, Auckland, Kathryn, additional, Cortes, Adrian, additional, Acuna-Alonzo, Victor, additional, Ioannidis, Alexander G, additional, Gignoux, Christopher R, additional, Wojcik, Genevieve L, additional, Fernandez-Valverde, Selene L, additional, Hill, Adrian V.S., additional, Tusie-Luna, Maria Teresa, additional, Mentzer, Alexander J, additional, Novembre, John, additional, Garcia-Garcia, Lourdes, additional, and Moreno-Estrada, Andres, additional
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- 2022
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14. Getting genetic ancestry right for science and society
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Lewis, Anna C. F., primary, Molina, Santiago J., additional, Appelbaum, Paul S., additional, Dauda, Bege, additional, Di Rienzo, Anna, additional, Fuentes, Agustin, additional, Fullerton, Stephanie M., additional, Garrison, Nanibaa’ A., additional, Ghosh, Nayanika, additional, Hammonds, Evelynn M., additional, Jones, David S., additional, Kenny, Eimear E., additional, Kraft, Peter, additional, Lee, Sandra S.-J., additional, Mauro, Madelyn, additional, Novembre, John, additional, Panofsky, Aaron, additional, Sohail, Mashaal, additional, Neale, Benjamin M., additional, and Allen, Danielle S., additional
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- 2022
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15. Editor's evaluation: Native American genetic ancestry and pigmentation allele contributions to skin color in a Caribbean population
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Sohail, Mashaal, primary
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- 2022
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16. Editorial: Genetic Architecture and Evolution of Complex Traits and Diseases in Diverse Human Populations
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Ortega-Del Vecchyo, Diego, primary, Berg, Jeremy, additional, and Sohail, Mashaal, additional
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- 2022
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17. The trait specific timing of accelerated genomic change in the human lineage
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Kun, Eucharist, primary, Sohail, Mashaal, additional, and Narasimhan, Vagheesh M., additional
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- 2022
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18. Populations, Traits, and Their Spatial Structure in Humans
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Sohail, Mashaal, Izarraras-Gomez, Alan, and Ortega-Del Vecchyo, Diego
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AcademicSubjects/SCI01140 ,Geography ,AcademicSubjects/SCI01130 ,spatial variation ,Genetic Variation ,Review ,populations ,complex traits ,Phenotype ,genetic structure ,Genetics ,Humans ,Selection, Genetic ,Alleles ,Ecology, Evolution, Behavior and Systematics - Abstract
The spatial distribution of genetic variants is jointly determined by geography, past demographic processes, natural selection, and its interplay with environmental variation. A fraction of these genetic variants are “causal alleles” that affect the manifestation of a complex trait. The effect exerted by these causal alleles on complex traits can be independent or dependent on the environment. Understanding the evolutionary processes that shape the spatial structure of causal alleles is key to comprehend the spatial distribution of complex traits. Natural selection, past population size changes, range expansions, consanguinity, assortative mating, archaic introgression, admixture, and the environment can alter the frequencies, effect sizes, and heterozygosities of causal alleles. This provides a genetic axis along which complex traits can vary. However, complex traits also vary along biogeographical and sociocultural axes which are often correlated with genetic axes in complex ways. The purpose of this review is to consider these genetic and environmental axes in concert and examine the ways they can help us decipher the variation in complex traits that is visible in humans today. This initiative necessarily implies a discussion of populations, traits, the ability to infer and interpret “genetic” components of complex traits, and how these have been impacted by adaptive events. In this review, we provide a history-aware discussion on these topics using both the recent and more distant past of our academic discipline and its relevant contexts.
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- 2021
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19. Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes
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Jiménez-Kaufmann, Andrés, primary, Chong, Amanda Y., additional, Cortés, Adrián, additional, Quinto-Cortés, Consuelo D., additional, Fernandez-Valverde, Selene L., additional, Ferreyra-Reyes, Leticia, additional, Cruz-Hervert, Luis Pablo, additional, Medina-Muñoz, Santiago G., additional, Sohail, Mashaal, additional, Palma-Martinez, María J., additional, Delgado-Sánchez, Gudalupe, additional, Mongua-Rodríguez, Norma, additional, Mentzer, Alexander J., additional, Hill, Adrian V. S., additional, Moreno-Macías, Hortensia, additional, Huerta-Chagoya, Alicia, additional, Aguilar-Salinas, Carlos A., additional, Torres, Michael, additional, Kim, Hie Lim, additional, Kalsi, Namrata, additional, Schuster, Stephan C., additional, Tusié-Luna, Teresa, additional, Del-Vecchyo, Diego Ortega, additional, García-García, Lourdes, additional, and Moreno-Estrada, Andrés, additional
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- 2022
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20. Ancestry: How Researchers Use It, and What They Mean by It
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Dauda, Bege, primary, Molina, Santiago J., additional, Allen, Danielle, additional, Fuentes, Agustin, additional, Ghosh, Nayanika, additional, Mauro, Madelyn, additional, Neale, Benjamin M., additional, Panofsky, Aaron, additional, Sohail, Mashaal, additional, Zhang, Sarah, additional, and Lewis, Anna, additional
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- 2022
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21. Editor's evaluation: Body mass index and childhood symptoms of depression, anxiety, and attention-deficit hyperactivity disorder: A within-family Mendelian randomization study
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Sohail, Mashaal, primary
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- 2021
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22. Editor's evaluation: Regulatory dissection of the severe COVID-19 risk locus introgressed by Neanderthals
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Sohail, Mashaal, primary
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- 2021
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23. Decision letter: Recent shifts in the genomic ancestry of Mexican Americans may alter the genetic architecture of biomedical traits
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Sohail, Mashaal, additional and Wojcik, Genevieve L, additional
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- 2020
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24. WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene
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Nersisyan, Lilit, Nikoghosyan, Maria, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Elbers, Clara C., Kloosterman, Wigard P., van Setten, Jessica, Nijman, Isaac J., Renkens, Ivo, de Bakker, Paul I. W., van Dijk, Freerk, Neerincx, Pieter B. T., Deelen, Patrick, Kanterakis, Alexandros, Dijkstra, Martijn, Byelas, Heorhiy, van der Velde, K. Joeri, Platteel, Mathieu, Swertz, Morris A., Wijmenga, Cisca, Palamara, Pier Francesco, Pe'er, Itsik, Ye, Kai, Lameijer, Eric-Wubbo, Moed, Matthijs H., Beekman, Marian, de Craen, Anton J. M., Suchiman, H. Eka D., Slagboom, P. Eline, Guryev, Victor, Abdellaoui, Abdel, Hottenga, Jouke Jan, Kattenberg, Mathijs, Willemsen, Gonneke, Boomsma, Dorret I., van Leeuwen, Elisabeth M., Karssen, Lennart C., Amin, Najaf, Rivadeneira, Fernando, Isaacs, Aaron, Hofman, Albert, Uitterlinden, Andre G., van Duijn, Cornelia M., van Oven, Mannis, Kayser, Manfred, Vermaat, Martijn, Laros, Jeroen F. J., den Dunnen, Johan T., van Enckevort, David, Mei, Hailiang, Li, Mingkun, Stoneking, Mark, van Schaik, Barbera D. C., Bot, Jan, Marschall, Tobias, Schonhuth, Alexander, Hehir-Kwa, Jayne Y., Handsaker, Robert E., Polak, Paz, Sohail, Mashaal, Vuzman, Dana, Estrada, Karol, McCarroll, Steven A., Sunyaev, Shamil R., Hormozdiari, Fereydoun, Koval, Vyacheslav, Medina-Gomez, Carolina, Oostra, Ben, Veldink, Jan H., van den Berg, Leonard H., Pitts, Steven J., Potluri, Shobha, Sundar, Purnima, Cox, David R., de Knijff, Peter, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Wang, Jun, Li, Ning, Cao, Sujie, Bovenberg, Jasper A., van Ommen, Gert-Jan B., Arakelyan, Arsen, Nersisyan, Lilit, Nikoghosyan, Maria, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Elbers, Clara C., Kloosterman, Wigard P., van Setten, Jessica, Nijman, Isaac J., Renkens, Ivo, de Bakker, Paul I. W., van Dijk, Freerk, Neerincx, Pieter B. T., Deelen, Patrick, Kanterakis, Alexandros, Dijkstra, Martijn, Byelas, Heorhiy, van der Velde, K. Joeri, Platteel, Mathieu, Swertz, Morris A., Wijmenga, Cisca, Palamara, Pier Francesco, Pe'er, Itsik, Ye, Kai, Lameijer, Eric-Wubbo, Moed, Matthijs H., Beekman, Marian, de Craen, Anton J. M., Suchiman, H. Eka D., Slagboom, P. Eline, Guryev, Victor, Abdellaoui, Abdel, Hottenga, Jouke Jan, Kattenberg, Mathijs, Willemsen, Gonneke, Boomsma, Dorret I., van Leeuwen, Elisabeth M., Karssen, Lennart C., Amin, Najaf, Rivadeneira, Fernando, Isaacs, Aaron, Hofman, Albert, Uitterlinden, Andre G., van Duijn, Cornelia M., van Oven, Mannis, Kayser, Manfred, Vermaat, Martijn, Laros, Jeroen F. J., den Dunnen, Johan T., van Enckevort, David, Mei, Hailiang, Li, Mingkun, Stoneking, Mark, van Schaik, Barbera D. C., Bot, Jan, Marschall, Tobias, Schonhuth, Alexander, Hehir-Kwa, Jayne Y., Handsaker, Robert E., Polak, Paz, Sohail, Mashaal, Vuzman, Dana, Estrada, Karol, McCarroll, Steven A., Sunyaev, Shamil R., Hormozdiari, Fereydoun, Koval, Vyacheslav, Medina-Gomez, Carolina, Oostra, Ben, Veldink, Jan H., van den Berg, Leonard H., Pitts, Steven J., Potluri, Shobha, Sundar, Purnima, Cox, David R., de Knijff, Peter, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Wang, Jun, Li, Ning, Cao, Sujie, Bovenberg, Jasper A., van Ommen, Gert-Jan B., and Arakelyan, Arsen
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- 2019
25. Fine-Scale Haplotype Structure Reveals Strong Signatures of Positive Selection in a Recombining Bacterial Pathogen
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Arnold, Brian, primary, Sohail, Mashaal, additional, Wadsworth, Crista, additional, Corander, Jukka, additional, Hanage, William P, additional, Sunyaev, Shamil, additional, and Grad, Yonatan H, additional
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- 2019
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26. Polygenic adaptation on height is overestimated due to uncorrected stratification in genome-wide association studies
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Sohail, Mashaal, primary, Maier, Robert M, additional, Ganna, Andrea, additional, Bloemendal, Alex, additional, Martin, Alicia R, additional, Turchin, Michael C, additional, Chiang, Charleston WK, additional, Hirschhorn, Joel, additional, Daly, Mark J, additional, Patterson, Nick, additional, Neale, Benjamin, additional, Mathieson, Iain, additional, Reich, David, additional, and Sunyaev, Shamil R, additional
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- 2019
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27. Author response: Polygenic adaptation on height is overestimated due to uncorrected stratification in genome-wide association studies
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Sohail, Mashaal, primary, Maier, Robert M, additional, Ganna, Andrea, additional, Bloemendal, Alex, additional, Martin, Alicia R, additional, Turchin, Michael C, additional, Chiang, Charleston WK, additional, Hirschhorn, Joel, additional, Daly, Mark J, additional, Patterson, Nick, additional, Neale, Benjamin, additional, Mathieson, Iain, additional, Reich, David, additional, and Sunyaev, Shamil R, additional
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- 2018
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28. Fine-Scale Haplotype Structure Reveals Strong Signatures of Positive Selection in a Recombining Bacterial Pathogen.
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Arnold, Brian, Sohail, Mashaal, Wadsworth, Crista, Corander, Jukka, Hanage, William P, Sunyaev, Shamil, and Grad, Yonatan H
- Abstract
Identifying genetic variation in bacteria that has been shaped by ecological differences remains an important challenge. For recombining bacteria, the sign and strength of linkage provide a unique lens into ongoing selection. We show that derived alleles <300 bp apart in Neisseria gonorrhoeae exhibit more coupling linkage than repulsion linkage, a pattern that cannot be explained by limited recombination or neutrality as these couplings are significantly stronger for nonsynonymous alleles than synonymous alleles. This general pattern is driven by a small fraction of highly diverse genes, many of which exhibit evidence of interspecies horizontal gene transfer and an excess of intermediate frequency alleles. Extensive simulations show that two distinct forms of positive selection can create these patterns of genetic variation: directional selection on horizontally transferred alleles or balancing selection that maintains distinct haplotypes in the presence of recombination. Our results establish a framework for identifying patterns of selection in fine-scale haplotype structure that indicate specific ecological processes in species that recombine with distantly related lineages or possess coexisting adaptive haplotypes. [ABSTRACT FROM AUTHOR]
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- 2020
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29. Signals of polygenic adaptation on height have been overestimated due to uncorrected population structure in genome-wide association studies
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Sohail, Mashaal, primary, Maier, Robert M., additional, Ganna, Andrea, additional, Bloemendal, Alex, additional, Martin, Alicia R., additional, Turchin, Michael C., additional, Chiang, Charleston W. K., additional, Hirschhorn, Joel N., additional, Daly, Mark J., additional, Patterson, Nick, additional, Neale, Benjamin M., additional, Mathieson, Iain, additional, Reich, David, additional, and Sunyaev, Shamil R., additional
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- 2018
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30. Negative selection in humans and fruit flies involves synergistic epistasis
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Neurogenetica, Circulatory Health, CMM Groep Kaaij, Projectafdeling ALS, Brain, Regenerative Medicine and Stem Cells, ZL Neuromusculaire Ziekten Medisch, Infection & Immunity, Sohail, Mashaal, Vakhrusheva, Olga A, Sul, Jae Hoon, Pulit, Sara L, Francioli, Laurent C, van den Berg, Leonard H, Veldink, Jan H, de Bakker, Paul I W, Bazykin, Georgii A, Kondrashov, Alexey S, Sunyaev, Shamil R, Genome of the Netherlands Consortium, Neurogenetica, Circulatory Health, CMM Groep Kaaij, Projectafdeling ALS, Brain, Regenerative Medicine and Stem Cells, ZL Neuromusculaire Ziekten Medisch, Infection & Immunity, Sohail, Mashaal, Vakhrusheva, Olga A, Sul, Jae Hoon, Pulit, Sara L, Francioli, Laurent C, van den Berg, Leonard H, Veldink, Jan H, de Bakker, Paul I W, Bazykin, Georgii A, Kondrashov, Alexey S, Sunyaev, Shamil R, and Genome of the Netherlands Consortium
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- 2017
31. Genes with monoallelic expression contribute disproportionately to genetic diversity in humans
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Savova, Virginia, primary, Chun, Sung, additional, Sohail, Mashaal, additional, McCole, Ruth B, additional, Witwicki, Robert, additional, Gai, Lisa, additional, Lenz, Tobias L, additional, Wu, C-ting, additional, Sunyaev, Shamil R, additional, and Gimelbrant, Alexander A, additional
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- 2016
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32. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels
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Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, and Bovenberg, Jasper A.
- Abstract
Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (∼35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value -4), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C =0.135, βTC =0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR.
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- 2015
33. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels
- Author
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CMM Groep Kaaij, CMM Groep Kloosterman, Child Health, Cancer, ZL Neuromusculaire Ziekten Medisch, Experimentele Afd. Cardiologie 1, CMM Groep Cuppen, JC onderzoeksprogramma Methodologie, Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., de Bakker, Paul I W, CMM Groep Kaaij, CMM Groep Kloosterman, Child Health, Cancer, ZL Neuromusculaire Ziekten Medisch, Experimentele Afd. Cardiologie 1, CMM Groep Cuppen, JC onderzoeksprogramma Methodologie, Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., and de Bakker, Paul I W
- Published
- 2015
34. Whole-genome sequence variation, population structure and demographic history of the Dutch population
- Author
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Francioli, Laurent C., Menelaou, Andronild, Pulit, Sara L., Van Dijk, Freerk, Palamara, Pier Francesco, Elbers, Clara C., Neerincx, Pieter B. T., Ye, Kai, Guryev, Victor, Kloosterman, Wigard P., Deelen, Patrick, Abdellaoui, Abdel, Van Leeuwen, Elisabeth M., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F. J., Karssen, Lennart C., Kanterakis, Alexandros, Amin, Najaf, Hottenga, Jouke Jan, Lameijer, Eric-Wubbo, Kattenberg, Mathijs, Dijkstra, Martijn, Byelas, Heorhiy, Van Settenl, Jessica, Van Schaik, Barbera D. C., Bot, Jan, Nijman, Isaac J., Renkens, Ivo, Marscha, Tobias, Schonhuth, Alexander, Hehir-Kwa, Jayne Y., Handsaker, Robert E., Polak, Paz, Sohail, Mashaal, Vuzman, Dana, Hormozdiari, Fereydoun, Van Enckevort, David, Mei, Hailiang, Koval, Vyacheslav, Moed, Ma-Tthijs H., Van der Velde, K. Joeri, Rivadeneira, Fernando, Estrada, Karol, Medina-Gomez, Carolina, Isaacs, Aaron, McCarroll, Steven A., Beekrnan, Marian, De Craen, Anton J. M., Suchiman, H. Eka D., Hofman, Albert, Oostra, Ben, Uitterlinden, Andre G., Willemsen, Gonneke, Plattee, Mathieu, Veldink, Jan H., Van den Berg, Leonard H., Pitts, Steven J., Potluri, Shobha, Sundar, Purnima, Cox, David R., Sunyaev, Shamil R., Den Dunnen, Johan T., Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., Peer, Itsik, Slagboom, P. Eline, Van Duijn, Cornelia M., Boomsma, Dorret I., Van Ommen, Gert-Jan B., De Bakker, Paul I. W., Swertz, Morris A., Wijmenga, Cisca, Francioli, Laurent C., Menelaou, Andronild, Pulit, Sara L., Van Dijk, Freerk, Palamara, Pier Francesco, Elbers, Clara C., Neerincx, Pieter B. T., Ye, Kai, Guryev, Victor, Kloosterman, Wigard P., Deelen, Patrick, Abdellaoui, Abdel, Van Leeuwen, Elisabeth M., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F. J., Karssen, Lennart C., Kanterakis, Alexandros, Amin, Najaf, Hottenga, Jouke Jan, Lameijer, Eric-Wubbo, Kattenberg, Mathijs, Dijkstra, Martijn, Byelas, Heorhiy, Van Settenl, Jessica, Van Schaik, Barbera D. C., Bot, Jan, Nijman, Isaac J., Renkens, Ivo, Marscha, Tobias, Schonhuth, Alexander, Hehir-Kwa, Jayne Y., Handsaker, Robert E., Polak, Paz, Sohail, Mashaal, Vuzman, Dana, Hormozdiari, Fereydoun, Van Enckevort, David, Mei, Hailiang, Koval, Vyacheslav, Moed, Ma-Tthijs H., Van der Velde, K. Joeri, Rivadeneira, Fernando, Estrada, Karol, Medina-Gomez, Carolina, Isaacs, Aaron, McCarroll, Steven A., Beekrnan, Marian, De Craen, Anton J. M., Suchiman, H. Eka D., Hofman, Albert, Oostra, Ben, Uitterlinden, Andre G., Willemsen, Gonneke, Plattee, Mathieu, Veldink, Jan H., Van den Berg, Leonard H., Pitts, Steven J., Potluri, Shobha, Sundar, Purnima, Cox, David R., Sunyaev, Shamil R., Den Dunnen, Johan T., Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., Peer, Itsik, Slagboom, P. Eline, Van Duijn, Cornelia M., Boomsma, Dorret I., Van Ommen, Gert-Jan B., De Bakker, Paul I. W., Swertz, Morris A., and Wijmenga, Cisca
- Published
- 2014
35. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses
- Author
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Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Ragon Institute of MGH, MIT and Harvard, Koch Institute for Integrative Cancer Research at MIT, Moon, James J., Suh, Heikyung, Bershteyn, Anna, Stephan, Matthias T., Liu, Haipeng, Huang, Bonnie, Sohail, Mashaal, Luo, Samantha, Ho Um, Soong, Irvine, Darrell J., Khant, Htet, Goodwin, Jessica T., Ramos, Jenelyn, Chiu, Wah, Irvine, Darrell J, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Ragon Institute of MGH, MIT and Harvard, Koch Institute for Integrative Cancer Research at MIT, Moon, James J., Suh, Heikyung, Bershteyn, Anna, Stephan, Matthias T., Liu, Haipeng, Huang, Bonnie, Sohail, Mashaal, Luo, Samantha, Ho Um, Soong, Irvine, Darrell J., Khant, Htet, Goodwin, Jessica T., Ramos, Jenelyn, Chiu, Wah, and Irvine, Darrell J
- Abstract
available in PMC 2011 September 1, Vaccines based on recombinant proteins avoid the toxicity and antivector immunity associated with live vaccine (for example, viral) vectors, but their immunogenicity is poor, particularly for CD8+ T-cell responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8+ T-cell responses comparable to those for live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. Interbilayer-crosslinked vesicles stably entrapped protein antigens in the vesicle core and lipid-based immunostimulatory molecules in the vesicle walls under extracellular conditions, but exhibited rapid release in the presence of endolysosomal lipases. We found that these antigen/adjuvant-carrying vesicles form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to those for the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for therapeutic protein delivery., Ragon Institute of MGH, MIT and Harvard, Bill & Melinda Gates Foundation, United States. Dept. of Defense (contract W911NF-07-D-0004), National Institutes of Health (U.S.) (P41RR002250), National Institutes of Health (U.S.) (RC2GM092599)
- Published
- 2013
36. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses
- Author
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Moon, James J., primary, Suh, Heikyung, additional, Bershteyn, Anna, additional, Stephan, Matthias T., additional, Liu, Haipeng, additional, Huang, Bonnie, additional, Sohail, Mashaal, additional, Luo, Samantha, additional, Ho Um, Soong, additional, Khant, Htet, additional, Goodwin, Jessica T., additional, Ramos, Jenelyn, additional, Chiu, Wah, additional, and Irvine, Darrell J., additional
- Published
- 2011
- Full Text
- View/download PDF
37. A framework for the detection of de novo mutations in family-based sequencing data
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Francioli, Laurent C, Cretu-Stancu, Mircea, Garimella, Kiran V, Fromer, Menachem, Kloosterman, Wigard P, Wijmenga, Cisca, Investigator, Principal, Swertz, Morris A, van Duijn, Cornelia M, Boomsma, Dorret I, Slagboom, PEline, van Ommen, Gertjan B, de Bakker, Paul IW, van Dijk, Freerk, Menelaou, Androniki, Neerincx, Pieter BT, Pulit, Sara L, Deelen, Patrick, Elbers, Clara C, Francesco Palamara, Pier, Pe'er, Itsik, Abdellaoui, Abdel, van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen FJ, Stoneking, Mark, de Knijff, Peter, Kayser, Manfred, Veldink, Jan H, van den Berg, Leonard H, Byelas, Heorhiy, den Dunnen, Johan T, Dijkstra, Martijn, Amin, Najaf, van der Velde, K Joeri, Hottenga, Jouke Jan, van Setten, Jessica, van Leeuwen, Elisabeth M, Kanterakis, Alexandros, Kattenberg, Mathijs, Karssen, Lennart C, van Schaik, Barbera DC, Bot, Jan, Nijman, Isaäc J, Renkens, Ivo, van Enckevort, David, Mei, Hailiang, Koval, Vyacheslav, Estrada, Karol, Medina-Gomez, Carolina, Ye, Kai, Lameijer, Eric-Wubbo, Moed, Matthijs H, Hehir-Kwa, Jayne Y, Handsaker, Robert E, McCarroll, Steven A, Sunyaev, Shamil R, Polak, Paz, Vuzman, Dana, Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Slagboom, P Eline, Beekman, Marian B, de Craen, Anton JM, Suchiman, H Eka D, Hofman, Albert, Oostra, Ben, Isaacs, Aaron, Rivadeneira, Fernando, Uitterlinden, André G, Willemsen, Gonneke, Platteel, Mathieu, Pitts, Steven J, Potluri, Shobha, Sundar, Purnima, Cox, David R, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A, Brandsma, Margreet, Samocha, Kaitlin E, Neale, Benjamin M, Daly, Mark J, Banks, Eric, and DePristo, Mark A
- Abstract
Germline mutation detection from human DNA sequence data is challenging due to the rarity of such events relative to the intrinsic error rates of sequencing technologies and the uneven coverage across the genome. We developed PhaseByTransmission (PBT) to identify de novo single nucleotide variants and short insertions and deletions (indels) from sequence data collected in parent-offspring trios. We compute the joint probability of the data given the genotype likelihoods in the individual family members, the known familial relationships and a prior probability for the mutation rate. Candidate de novo mutations (DNMs) are reported along with their posterior probability, providing a systematic way to prioritize them for validation. Our tool is integrated in the Genome Analysis Toolkit and can be used together with the ReadBackedPhasing module to infer the parental origin of DNMs based on phase-informative reads. Using simulated data, we show that PBT outperforms existing tools, especially in low coverage data and on the X chromosome. We further show that PBT displays high validation rates on empirical parent-offspring sequencing data for whole-exome data from 104 trios and X-chromosome data from 249 parent-offspring families. Finally, we demonstrate an association between father's age at conception and the number of DNMs in female offspring's X chromosome, consistent with previous literature reports.
- Published
- 2016
- Full Text
- View/download PDF
38. Improved imputation quality of low-frequency and rare variants in European samples using the ‘Genome of The Netherlands'
- Author
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Deelen, Patrick, Menelaou, Androniki, van Leeuwen, Elisabeth M, Kanterakis, Alexandros, van Dijk, Freerk, Medina-Gomez, Carolina, Francioli, Laurent C, Hottenga, Jouke Jan, Karssen, Lennart C, Estrada, Karol, Kreiner-Møller, Eskil, Rivadeneira, Fernando, van Setten, Jessica, Gutierrez-Achury, Javier, Westra, Harm-Jan, Franke, Lude, van Enckevort, David, Dijkstra, Martijn, Byelas, Heorhiy, van Duijn, Cornelia M, Swertz, Morris A, Neerincx, Pieter B T, Pulit, Sara L, Elbers, Clara C, Francesco Palamara, Pier, Pe'er, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P, van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, de Knijff, Peter, Kayser, Manfred, Veldink, Jan H, van den Berg, Leonard H, den Dunnen, Johan T, Amin, Najaf, van der Velde, K Joeri, Jan Hottenga, Jouke, Kattenberg, Mathijs, van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäuc J, Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric-Wubbo, Moed, Matthijs H, Hehir-Kwa, Jayne Y, Handsaker, Robert E, Sunyaev, Shamil R, Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Marschall, Schönhuth, Guryev, Victor, de Bakker, Paul I W, Slagboom, P Eline, Beekman, Marian B, de Craen, Anton J M, Suchiman, H Eka D, Hofman, Albert, van Duijn, Cornelia, Boomsma, Dorret I, Willemsen, Gonneke, Wolffenbuttel, Bruce H, Platteel, Mathieu, Pitts, Steven J, Potluri, Shobha, Cox, David R, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A, committee, Steering, Wijmenga, Cisca, and van Ommen, Gertjan B
- Subjects
genotype imputation ,GWAS ,GoNL ,rare variants ,reference sets ,reference panel - Abstract
Although genome-wide association studies (GWAS) have identified many common variants associated with complex traits, low-frequency and rare variants have not been interrogated in a comprehensive manner. Imputation from dense reference panels, such as the 1000 Genomes Project (1000G), enables testing of ungenotyped variants for association. Here we present the results of imputation using a large, new population-specific panel: the Genome of The Netherlands (GoNL). We benchmarked the performance of the 1000G and GoNL reference sets by comparing imputation genotypes with ‘true' genotypes typed on ImmunoChip in three European populations (Dutch, British, and Italian). GoNL showed significant improvement in the imputation quality for rare variants (MAF 0.05–0.5%) compared with 1000G. In Dutch samples, the mean observed Pearson correlation, r2, increased from 0.61 to 0.71. We also saw improved imputation accuracy for other European populations (in the British samples, r2 improved from 0.58 to 0.65, and in the Italians from 0.43 to 0.47). A combined reference set comprising 1000G and GoNL improved the imputation of rare variants even further. The Italian samples benefitted the most from this combined reference (the mean r2 increased from 0.47 to 0.50). We conclude that the creation of a large population-specific reference is advantageous for imputing rare variants and that a combined reference panel across multiple populations yields the best imputation results.
- Published
- 2014
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- View/download PDF
39. Global Signatures of Selection in Humans
- Author
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Sohail, Mashaal
- Subjects
- Biology, Genetics, Biology, Bioinformatics
- Abstract
This thesis studies the properties and prevalence of natural selection operating on our species on a global or genome-wide scale. It is still not known how negative selection against deleterious mutations operates genome-wide, whether balancing selection is responsible for maintaining higher genetic diversity in some parts of the genome, and how prevalent adaptation on complex or polygenic traits is in humans. We now have access to population genetic data from healthy populations worldwide, methods to evaluate the functional effects and age of genetic mutations, and Genome-wide Association (GWA) studies to estimate the genetic basis of a complex trait. Using these resources, as well as developing novel statistical methodologies, we show that 1) negative selection in humans involves synergistic epistasis, or deleterious mutations in the human genome interact globally in a manner to reinforce each other’s effects, 2) genes with monoallelic expression contribute disproportionately to genetic diversity in humans, which is maintained through the evolutionary forces of balancing selection and a higher mutation and recombination rate 3) the signal for polygenic adaptation at height-associated genetic variants in humans is confounded by ascertainment biases in the GWAS used to estimate height across populations. We conclude that (1) helps explain how humans tolerate a high incoming rate of deleterious mutations, and why sexual reproduction may have an evolutionary advantage, (2) establishes a link between genetic and epigenetic mechanisms of maintaining and exhibiting high genetic diversity in humans, and (3) demonstrates the presence of confounders that restrict interpretation of signals of polygenic adaptation in humans found using currently existing GWA studies.
- Published
- 2018
40. Natural selection acting on complex traits hampers the predictive accuracy of polygenic scores in ancient samples.
- Author
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Añorve-Garibay V, Huerta-Sanchez E, Sohail M, and Ortega-Del Vecchyo D
- Abstract
The prediction of phenotypes from ancient humans has gained interest due to its potential to investigate the evolution of complex traits. These predictions are commonly performed using polygenic scores computed with DNA information from ancient humans along with genome-wide association studies (GWAS) data from present-day humans. However, numerous evolutionary processes could impact the prediction of phenotypes from ancient humans based on polygenic scores. In this work we investigate how natural selection impacts phenotypic predictions on ancient individuals using polygenic scores. We use simulations of an additive trait to analyze how natural selection impacts phenotypic predictions with polygenic scores. We simulate a trait evolving under neutrality, stabilizing selection and directional selection. We find that stabilizing and directional selection have contrasting effects on ancient phenotypic predictions. Stabilizing selection accelerates the loss of large-effect alleles contributing to trait variation. Conversely, directional selection accelerates the loss of small and large-effect alleles that drive individuals farther away from the optimal phenotypic value. These effects result in specific shared genetic variation patterns between ancient and modern populations which hamper the accuracy of polygenic scores to predict phenotypes. Furthermore, we conducted simulations that include realistic strengths of stabilizing selection and heritability estimates to show how natural selection could impact the predictive accuracy of ancient polygenic scores for two widely studied traits: height and body mass index. We emphasize the importance of considering how natural selection can decrease the reliability of ancient polygenic scores to perform phenotypic predictions on an ancient population.
- Published
- 2024
- Full Text
- View/download PDF
41. The genetic architecture of the human skeletal form.
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Kun E, Javan EM, Smith O, Gulamali F, de la Fuente J, Flynn BI, Vajrala K, Trutner Z, Jayakumar P, Tucker-Drob EM, Sohail M, Singh T, and Narasimhan VM
- Abstract
The human skeletal form underlies our ability to walk on two legs, but unlike standing height, the genetic basis of limb lengths and skeletal proportions is less well understood. Here we applied a deep learning model to 31,221 whole body dual-energy X-ray absorptiometry (DXA) images from the UK Biobank (UKB) to extract 23 different image-derived phenotypes (IDPs) that include all long bone lengths as well as hip and shoulder width, which we analyzed while controlling for height. All skeletal proportions are highly heritable (∼40-50%), and genome-wide association studies (GWAS) of these traits identified 179 independent loci, of which 102 loci were not associated with height. These loci are enriched in genes regulating skeletal development as well as associated with rare human skeletal diseases and abnormal mouse skeletal phenotypes. Genetic correlation and genomic structural equation modeling indicated that limb proportions exhibited strong genetic sharing but were genetically independent of width and torso proportions. Phenotypic and polygenic risk score analyses identified specific associations between osteoarthritis (OA) of the hip and knee, the leading causes of adult disability in the United States, and skeletal proportions of the corresponding regions. We also found genomic evidence of evolutionary change in arm-to-leg and hip-width proportions in humans consistent with striking anatomical changes in these skeletal proportions in the hominin fossil record. In contrast to cardiovascular, auto-immune, metabolic, and other categories of traits, loci associated with these skeletal proportions are significantly enriched in human accelerated regions (HARs), and regulatory elements of genes differentially expressed through development between humans and the great apes. Taken together, our work validates the use of deep learning models on DXA images to identify novel and specific genetic variants affecting the human skeletal form and ties a major evolutionary facet of human anatomical change to pathogenesis.
- Published
- 2023
- Full Text
- View/download PDF
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