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Author

William Klitz

Other affiliations: Boston Children's Hospital, Novartis, University of Kansas  ...read more
Bio: William Klitz is an academic researcher from University of California, Berkeley. The author has contributed to research in topics: Population & Linkage disequilibrium. The author has an hindex of 48, co-authored 114 publications receiving 10638 citations. Previous affiliations of William Klitz include Boston Children's Hospital & Novartis.


Papers
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Journal ArticleDOI
Swapan Mallick1, Swapan Mallick2, Swapan Mallick3, Heng Li3, Mark Lipson2, Iain Mathieson2, Melissa Gymrek, Fernando Racimo4, Mengyao Zhao2, Mengyao Zhao3, Mengyao Zhao1, Niru Chennagiri3, Niru Chennagiri2, Niru Chennagiri1, Susanne Nordenfelt1, Susanne Nordenfelt3, Susanne Nordenfelt2, Arti Tandon3, Arti Tandon2, Pontus Skoglund2, Pontus Skoglund3, Iosif Lazaridis2, Iosif Lazaridis3, Sriram Sankararaman5, Sriram Sankararaman2, Sriram Sankararaman3, Qiaomei Fu2, Qiaomei Fu3, Qiaomei Fu6, Nadin Rohland2, Nadin Rohland3, Gabriel Renaud7, Yaniv Erlich8, Thomas Willems9, Carla Gallo10, Jeffrey P. Spence4, Yun S. Song11, Yun S. Song4, Giovanni Poletti10, Francois Balloux12, George van Driem13, Peter de Knijff14, Irene Gallego Romero15, Aashish R. Jha16, Doron M. Behar17, Claudio M. Bravi18, Cristian Capelli19, Tor Hervig20, Andrés Moreno-Estrada, Olga L. Posukh21, Elena Balanovska, Oleg Balanovsky22, Sena Karachanak-Yankova23, Hovhannes Sahakyan17, Hovhannes Sahakyan24, Draga Toncheva23, Levon Yepiskoposyan24, Chris Tyler-Smith25, Yali Xue25, M. Syafiq Abdullah26, Andres Ruiz-Linares12, Cynthia M. Beall27, Anna Di Rienzo16, Choongwon Jeong16, Elena B. Starikovskaya, Ene Metspalu28, Ene Metspalu17, Jüri Parik17, Richard Villems29, Richard Villems17, Richard Villems28, Brenna M. Henn30, Ugur Hodoglugil31, Robert W. Mahley32, Antti Sajantila33, George Stamatoyannopoulos34, Joseph Wee, Rita Khusainova35, Elza Khusnutdinova35, Sergey Litvinov35, Sergey Litvinov17, George Ayodo36, David Comas37, Michael F. Hammer38, Toomas Kivisild39, Toomas Kivisild17, William Klitz, Cheryl A. Winkler40, Damian Labuda41, Michael J. Bamshad34, Lynn B. Jorde42, Sarah A. Tishkoff11, W. Scott Watkins42, Mait Metspalu17, Stanislav Dryomov, Rem I. Sukernik43, Lalji Singh5, Lalji Singh44, Kumarasamy Thangaraj44, Svante Pääbo7, Janet Kelso7, Nick Patterson3, David Reich1, David Reich2, David Reich3 
13 Oct 2016-Nature
TL;DR: It is demonstrated that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.
Abstract: Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.

1,133 citations

Journal ArticleDOI
Iosif Lazaridis1, Iosif Lazaridis2, Nick Patterson2, Alissa Mittnik3, Gabriel Renaud4, Swapan Mallick1, Swapan Mallick2, Karola Kirsanow5, Peter H. Sudmant6, Joshua G. Schraiber7, Joshua G. Schraiber6, Sergi Castellano4, Mark Lipson8, Bonnie Berger2, Bonnie Berger8, Christos Economou9, Ruth Bollongino5, Qiaomei Fu4, Kirsten I. Bos3, Susanne Nordenfelt2, Susanne Nordenfelt1, Heng Li2, Heng Li1, Cesare de Filippo4, Kay Prüfer4, Susanna Sawyer4, Cosimo Posth3, Wolfgang Haak10, Fredrik Hallgren11, Elin Fornander11, Nadin Rohland1, Nadin Rohland2, Dominique Delsate12, Michael Francken3, Jean-Michel Guinet12, Joachim Wahl, George Ayodo, Hamza A. Babiker13, Hamza A. Babiker14, Graciela Bailliet, Elena Balanovska, Oleg Balanovsky, Ramiro Barrantes15, Gabriel Bedoya16, Haim Ben-Ami17, Judit Bene18, Fouad Berrada19, Claudio M. Bravi, Francesca Brisighelli20, George B.J. Busby21, Francesco Calì, Mikhail Churnosov22, David E. C. Cole23, Daniel Corach24, Larissa Damba, George van Driem25, Stanislav Dryomov26, Jean-Michel Dugoujon27, Sardana A. Fedorova28, Irene Gallego Romero29, Marina Gubina, Michael F. Hammer30, Brenna M. Henn31, Tor Hervig32, Ugur Hodoglugil33, Aashish R. Jha29, Sena Karachanak-Yankova34, Rita Khusainova35, Elza Khusnutdinova35, Rick A. Kittles30, Toomas Kivisild36, William Klitz7, Vaidutis Kučinskas37, Alena Kushniarevich38, Leila Laredj39, Sergey Litvinov38, Theologos Loukidis40, Theologos Loukidis41, Robert W. Mahley42, Béla Melegh18, Ene Metspalu43, Julio Molina, Joanna L. Mountain, Klemetti Näkkäläjärvi44, Desislava Nesheva34, Thomas B. Nyambo45, Ludmila P. Osipova, Jüri Parik43, Fedor Platonov28, Olga L. Posukh, Valentino Romano46, Francisco Rothhammer47, Francisco Rothhammer48, Igor Rudan14, Ruslan Ruizbakiev49, Hovhannes Sahakyan38, Hovhannes Sahakyan50, Antti Sajantila51, Antonio Salas52, Elena B. Starikovskaya26, Ayele Tarekegn, Draga Toncheva34, Shahlo Turdikulova49, Ingrida Uktveryte37, Olga Utevska53, René Vasquez54, Mercedes Villena54, Mikhail Voevoda55, Cheryl A. Winkler56, Levon Yepiskoposyan50, Pierre Zalloua57, Pierre Zalloua1, Tatijana Zemunik58, Alan Cooper10, Cristian Capelli21, Mark G. Thomas41, Andres Ruiz-Linares41, Sarah A. Tishkoff59, Lalji Singh60, Kumarasamy Thangaraj61, Richard Villems62, Richard Villems43, Richard Villems38, David Comas63, Rem I. Sukernik26, Mait Metspalu38, Matthias Meyer4, Evan E. Eichler6, Joachim Burger5, Montgomery Slatkin7, Svante Pääbo4, Janet Kelso4, David Reich2, David Reich64, David Reich1, Johannes Krause4, Johannes Krause3 
Harvard University1, Broad Institute2, University of Tübingen3, Max Planck Society4, University of Mainz5, University of Washington6, University of California, Berkeley7, Massachusetts Institute of Technology8, Stockholm University9, University of Adelaide10, The Heritage Foundation11, National Museum of Natural History12, Sultan Qaboos University13, University of Edinburgh14, University of Costa Rica15, University of Antioquia16, Rambam Health Care Campus17, University of Pécs18, Al Akhawayn University19, Catholic University of the Sacred Heart20, University of Oxford21, Belgorod State University22, University of Toronto23, University of Buenos Aires24, University of Bern25, Russian Academy of Sciences26, Paul Sabatier University27, North-Eastern Federal University28, University of Chicago29, University of Arizona30, Stony Brook University31, University of Bergen32, Illumina33, Sofia Medical University34, Bashkir State University35, University of Cambridge36, Vilnius University37, Estonian Biocentre38, University of Strasbourg39, Amgen40, University College London41, Gladstone Institutes42, University of Tartu43, University of Oulu44, Muhimbili University of Health and Allied Sciences45, University of Palermo46, University of Tarapacá47, University of Chile48, Academy of Sciences of Uzbekistan49, Armenian National Academy of Sciences50, University of North Texas51, University of Santiago de Compostela52, University of Kharkiv53, Higher University of San Andrés54, Novosibirsk State University55, Leidos56, Lebanese American University57, University of Split58, University of Pennsylvania59, Banaras Hindu University60, Centre for Cellular and Molecular Biology61, Estonian Academy of Sciences62, Pompeu Fabra University63, Howard Hughes Medical Institute64
18 Sep 2014-Nature
TL;DR: It is shown that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians; and early European farmers, who were mainly of Near Eastern origin but also harboured west Europeanhunter-gatherer related ancestry.
Abstract: We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.

1,077 citations

Journal ArticleDOI
David Reich1, David Reich2, Nick Patterson2, Desmond Campbell3, Desmond Campbell4, Arti Tandon2, Arti Tandon1, Stéphane Mazières5, Stéphane Mazières4, Nicolas Ray6, María Victoria Parra4, María Victoria Parra7, Winston Rojas7, Winston Rojas4, Constanza Duque7, Constanza Duque4, Natalia Mesa4, Natalia Mesa7, Luis F. García7, Omar Triana7, Silvia Blair7, Amanda Maestre7, Juan Carlos Dib, Claudio M. Bravi8, Claudio M. Bravi4, Graciela Bailliet8, Daniel Corach9, Tábita Hünemeier10, Tábita Hünemeier4, Maria Cátira Bortolini10, Francisco M. Salzano10, Maria Luiza Petzl-Erler11, Victor Acuña-Alonzo, Carlos A. Aguilar-Salinas, Samuel Canizales-Quinteros12, Teresa Tusié-Luna12, Laura Riba12, Maricela Rodríguez-Cruz13, Mardia López-Alarcón13, Ramón Mauricio Coral-Vázquez14, Thelma Canto-Cetina, Irma Silva-Zolezzi15, Juan Carlos Fernández-López, Alejandra V. Contreras, Gerardo Jimenez-Sanchez15, María José Gómez-Vázquez16, Julio Molina, Angel Carracedo17, Antonio Salas17, Carla Gallo18, Giovanni Poletti18, David B. Witonsky19, Gorka Alkorta-Aranburu19, Rem I. Sukernik20, Ludmila P. Osipova20, Sardana A. Fedorova, René Vasquez, Mercedes Villena, Claudia Moreau21, Ramiro Barrantes22, David L. Pauls1, Laurent Excoffier23, Laurent Excoffier24, Gabriel Bedoya7, Francisco Rothhammer25, Jean-Michel Dugoujon26, Georges Larrouy26, William Klitz27, Damian Labuda21, Judith R. Kidd28, Kenneth K. Kidd28, Anna Di Rienzo19, Nelson B. Freimer29, Alkes L. Price1, Alkes L. Price2, Andres Ruiz-Linares4 
16 Aug 2012-Nature
TL;DR: It is shown that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America.
Abstract: The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.

696 citations

Journal ArticleDOI
TL;DR: Evidence is observed of a higher level of diversity and lower level of population structure in western South America compared to eastern South America, a relative lack of differentiation between Mesoamerican and Andean populations, and a partial agreement on a local scale between genetic similarity and the linguistic classification of populations.
Abstract: We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. These data were analyzed jointly with similar data available in 54 other indigenous populations worldwide, including an additional five Native American groups. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians—signals of the southward dispersal of human populations from the northwestern tip of the Americas. We also observe evidence of: (1) a higher level of diversity and lower level of population structure in western South America compared to eastern South America, (2) a relative lack of differentiation between Mesoamerican and Andean populations, (3) a scenario in which coastal routes were easier for migrating peoples to traverse in comparison with inland routes, and (4) a partial agreement on a local scale between genetic similarity and the linguistic classification of populations. These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas.

542 citations

Journal Article
TL;DR: An increase in HLA class II alleles in 180 Caucasian nuclear families with at least two children with insulin-dependent diabetes mellitus (IDDM) is indicated and the complex, multigenic nature of HLAclass II-associated IDDM susceptibility is evident from these data.
Abstract: We report here our analysis of HLA class II alleles in 180 Caucasian nuclear families with at least two children with insulin-dependent diabetes mellitus (IDDM). DRB1, DQA1, DQB1, and DPB1 genotypes were determined with PCR/sequence-specific oligonucleotide probe typing methods. The data allowed unambiguous determination of four-locus haplotypes in all but three of the families. Consistent with other studies, our data indicate an increase in DR3/DR4, DR3/DR3, and DR4/DR4 genotypes in patients compared to controls. In addition, we found an increase in DR1/DR4, DR1/DR3, and DR4/DR8 genotypes. While the frequency of DQB1*0302 on DR4 haplotypes is dramatically increased in DR3/DR4 patients, DR4 haplotypes in DR1/DR4 patients exhibit frequencies of DQB1*0302 and DQB1*0301 more closely resembling those in control populations. The protective effect of DR2 is evident in this data set and is limited to the common DRB1*1501-DQB1*0602 haplotype. Most DR2+ patients carry the less common DR2 haplotype DRB1*1601-DQB1*0502, which is not decreased in patients relative to controls. DPB1 also appears to play a role in disease susceptibility. DPB1*0301 is increased in patients (P < .001) and may contribute to the disease risk of a number of different DR-DQ haplotypes. DPB1*0101, found almost exclusively on DR3 haplotypes in patients, is slightly increased, and maternal transmissions of DRB1*0301-DPB1*0101 haplotypes to affected children occur twice as frequently as do paternal transmissions. Transmissions of DR3 haplotypes carrying other DPB1 alleles occur at approximately equal maternal and paternal frequencies. The complex, multigenic nature of HLA class II-associated IDDM susceptibility is evident from these data.

451 citations


Cited by
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Journal Article
Fumio Tajima1
30 Oct 1989-Genomics
TL;DR: It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.

11,521 citations

Journal Article
TL;DR: The statistical basis for this "transmission test for linkage disequilibrium" (transmission/disequilibrium test] is described and the relationship of this test to tests of cosegregation that are based on the proportion of haplotypes or genes identical by descent in affected sibs is shown.
Abstract: A population association has consistently been observed between insulin-dependent diabetes mellitus (IDDM) and the "class 1" alleles of the region of tandem-repeat DNA (5' flanking polymorphism [5'FP]) adjacent to the insulin gene on chromosome 11p. This finding suggests that the insulin gene region contains a gene or genes contributing to IDDM susceptibility. However, several studies that have sought to show linkage with IDDM by testing for cosegregation in affected sib pairs have failed to find evidence for linkage. As means for identifying genes for complex diseases, both the association and the affected-sib-pairs approaches have limitations. It is well known that population association between a disease and a genetic marker can arise as an artifact of population structure, even in the absence of linkage. On the other hand, linkage studies with modest numbers of affected sib pairs may fail to detect linkage, especially if there is linkage heterogeneity. We consider an alternative method to test for linkage with a genetic marker when population association has been found. Using data from families with at least one affected child, we evaluate the transmission of the associated marker allele from a heterozygous parent to an affected offspring. This approach has been used by several investigators, but the statistical properties of the method as a test for linkage have not been investigated. In the present paper we describe the statistical basis for this "transmission test for linkage disequilibrium" (transmission/disequilibrium test [TDT]). We then show the relationship of this test to tests of cosegregation that are based on the proportion of haplotypes or genes identical by descent in affected sibs. The TDT provides strong evidence for linkage between the 5'FP and susceptibility to IDDM. The conclusions from this analysis apply in general to the study of disease associations, where genetic markers are usually closely linked to candidate genes. When a disease is found to be associated with such a marker, the TDT may detect linkage even when haplotype-sharing tests do not.

3,791 citations

Journal ArticleDOI
TL;DR: The Discriminant Analysis of Principal Components (DAPC) is introduced, a multivariate method designed to identify and describe clusters of genetically related individuals that performs generally better than STRUCTURE at characterizing population subdivision.
Abstract: The dramatic progress in sequencing technologies offers unprecedented prospects for deciphering the organization of natural populations in space and time. However, the size of the datasets generated also poses some daunting challenges. In particular, Bayesian clustering algorithms based on pre-defined population genetics models such as the STRUCTURE or BAPS software may not be able to cope with this unprecedented amount of data. Thus, there is a need for less computer-intensive approaches. Multivariate analyses seem particularly appealing as they are specifically devoted to extracting information from large datasets. Unfortunately, currently available multivariate methods still lack some essential features needed to study the genetic structure of natural populations. We introduce the Discriminant Analysis of Principal Components (DAPC), a multivariate method designed to identify and describe clusters of genetically related individuals. When group priors are lacking, DAPC uses sequential K-means and model selection to infer genetic clusters. Our approach allows extracting rich information from genetic data, providing assignment of individuals to groups, a visual assessment of between-population differentiation, and contribution of individual alleles to population structuring. We evaluate the performance of our method using simulated data, which were also analyzed using STRUCTURE as a benchmark. Additionally, we illustrate the method by analyzing microsatellite polymorphism in worldwide human populations and hemagglutinin gene sequence variation in seasonal influenza. Analysis of simulated data revealed that our approach performs generally better than STRUCTURE at characterizing population subdivision. The tools implemented in DAPC for the identification of clusters and graphical representation of between-group structures allow to unravel complex population structures. Our approach is also faster than Bayesian clustering algorithms by several orders of magnitude, and may be applicable to a wider range of datasets.

3,770 citations

Journal ArticleDOI
01 Feb 2011-Stroke
TL;DR: Evidence-based recommendations are included for the control of risk factors, interventional approaches to atherosclerotic disease of the cervicocephalic circulation, and antithrombotic treatments for preventing thrombosis and thromboembolic stroke.
Abstract: The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of stroke among individuals who have not previously experienced a stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches to atherosclerotic disease of the cervicocephalic circulation, and antithrombotic treatments for preventing thrombotic and thromboembolic stroke. Further recommendations are provided for genetic and pharmacogenetic testing and for the prevention of stroke in a variety of other specific circumstances, including sickle cell disease and patent foramen ovale.

2,299 citations