Eric S. Lander, Lauren M. Linton, Bruce Birren, Chad Nusbaum, Michael C. Zody, Jennifer Baldwin, Keri Devon, Ken Dewar, Michael Doyle, William FitzHugh, Roel Funke, Diane Gage The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
Journal: Nature , vol. 409, no. 6822, pp. 860-921, 2001 Todd R. Golub, Donna K. Slonim, Pablo Tamayo, C. Huard, M. Gaasenbeek, Jill P. Mesirov, H. Coller, Mignon L. Loh,James R. Downing, M. A. Caligiuri, C. D. Bloomfield, Eric S. Lander Although cancer classiTcation has improved over the past 30 years, there has been no general approach for identifying new cancer classes (class discovery)or for assigning tumors to known classes (class prediction). Here, a generic approach to cancer classiTcation based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case.A ...
Journal: Science , vol. 286, no. 5439, pp. 531-537, 1999 Journal: Genomics , vol. 1, no. 2, pp. 174-181, 1987 E. Lander
Published in 1995.
Stacey B. Gabriel, Stephen F. Schaffner, Huy Nguyen, Jamie M. Moore, Jessica Roy, Brendan Blumenstiel, John Higgins,Matthew DeFelice, Amy Lochner, Maura Faggart, Shau Neen Liu-Cordero, Charles RotimiEric S. Lander Haplotype-based methods offer a powerful approach to disease gene mapping, based on the association between causal mutations and the ancestral haplotypes on which they arose. As part of The SNP Consortium Allele Frequency Projects, we characterized haplotype patterns across 51 autosomal regions (spanning 13 megabases of the human genome) in samples from Africa, Europe, and Asia. We show that ...
Journal: Science , vol. 296, no. 5576, pp. 2225-2229, 2002 Robert H. Waterston, Kerstin Lindblad-Toh, Ewan Birney, Jane Rogers, Josep F. Abril, Pankaj Agarwal, Richa Agarwala,Rachel Ainscough, Marina Alexandersson, Peter An, Stylianos E. Antonarakis, John AttwoodEric S. Lander The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, ...
Journal: Nature , vol. 420, no. 6915, pp. 520-562, 2002 E. S. Lander, D. Botstein Published in 1989.
E. S. Lander, N. J. Schork Journal: Science , vol. 265, no. 5181, pp. 2037-2048, 1994 Array technologies have made it straightforward to monitor simultaneously the expression pattern of thousands of genes. The challenge now is to interpret such massive data sets. The first step is to extract the fundamental patterns of gene expression inherent in the data. This paper describes the application of self-organizing maps, a type of mathematical cluster analysis that is particularly ...
In complex disease studies, it is crucial to perform multipoint linkage analysis with many markers and to use robust nonparametric methods that take account of all pedigree information. Currently available methods fall short in both regards. In this paper, we describe how to extract complete multipoint inheritance information from general pedigrees of moderate size. This information is captured in the ...
Vamsi K Mootha, Cecilia M Lindgren, Karl-Fredrik Eriksson, Aravind Subramanian, Smita Sihag, Joseph Lehar, Pere Puigserver, Emma Carlsson, Martin Ridderstråle, Esa Laurila, Nicholas Houstis, Mark J DalyEric S Lander DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a ...
Identifying the functional elements encoded in a genome is one of the principal challenges in modern biology. Comparative genomics should offer a powerful, general approach. Here, we present a comparative analysis of the yeast Saccharomyces cerevisiae based on high-quality draft sequences of three related species (S. paradoxus, S. mikatae and S. bayanus). We first aligned the genomes and characterized ...
Journal: Nature , vol. 423, no. 6937, pp. 241-254, 2003 Christopher T. Harbison, D. Benjamin Gordon, Tong Ihn Lee, Nicola J. Rinaldi, Kenzie D. Macisaac, Timothy W. Danford,Nancy M. Hannett, Jean-Bosco Tagne, David B. Reynolds, Jane Yoo, Ezra G. Jennings, Julia ZeitlingerEric S. Lander DNA-binding transcriptional regulators interpret the genome's regulatory code by binding to specific sequences to induce or repress gene expression. Comparative genomics has recently been used to identify potential cis-regulatory sequences within the yeast genome on the basis of phylogenetic conservation, but this information alone does not reveal if or when transcriptional regulators occupy these binding sites. We ...
Journal: Nature , vol. 431, no. 7004, pp. 99-104, 2004 Association studies offer a potentially powerful approach to identify genetic variants that influence susceptibility to com- mon disease1-4, but are plagued by the impression that they are not consistently reproducible5,6. In principle, the inconsis- tency may be due to false positive studies, false negative stud- ies or true variability in association among different populations4-8. The critical question ...
MARGARET A. SHIPP, KEN N. ROSS, PABLO TAMAYO, ANDREW P. WENG, JEFFERY L. KUTOK, RICARDO C. T. AGUIAR, MICHELLE GAASENBEEK, MICHAEL ANGELO, MICHAEL REICH, GERALDINE S. PINKUS, TANE S. RAY,MARGARET A. KOVALERIC S. LANDER Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable in less than 50% of patients. Prognostic models based on pre-treatment characteristics, such as the International Prognostic Index (IPI), are currently used to predict outcome in DLBCL. However, clinical outcome models identify neither the molecular basis of clinical heterogeneity, nor specific therapeutic targets. We ...
Published in 2002.
Published in 2003.
Genome-wide expression analysis was used to identify genes whose expression depends on the functions of key components of the transcription initiation machinery in yeast. Components of the RNA polymerase II holoenzyme, the general transcription factor TFIID, and the SAGA chromatin modification complex were found to have roles in expression of distinct sets of genes. The results reveal an unanticipated ...
Journal: Cell , vol. 95, no. 5, pp. 717-728, 1998 Scott L. Pomeroy, Pablo Tamayo, Michelle Gaasenbeek, Lisa M. Sturla, Michael Angelo, Margaret E. McLaughlin, John Y. H. Kim, Liliana C. Goumnerova, Peter M. Black, Ching Lau, Jeffrey C. Allen, David ZagzagEric S. Lander Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' ...
Journal: Nature , vol. 415, no. 6870, pp. 436-442, 2002 Bradley E. Bernstein, Tarjei S. Mikkelsen, Xiaohui Xie, Michael Kamal, Dana J. Huebert, James Cuff, Ben Fry, Alex Meissner, Marius Wernig, Kathrin Plath, Rudolf Jaenisch, Alexandre WagschalEric S. Lander SUMMARY The most highly conserved noncoding ele- ments (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding de- velopmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified ...
Journal: Cell , vol. 125, no. 2, pp. 315-326, 2006 Ravi Sachidanandam, David Weissman, Steven C. Schmidt, Jerzy M. Kakol, Lincoln D. Stein, Gabor Marth, Steve Sherry,James C. Mullikin, Beverley J. Mortimore, David L. Willey, Sarah E. Hunt, Charlotte G. ColeEric S. Lander We describe a map of 1.42 million single nucleotide polymorphisms (SNPs) distributed throughout the human genome, providing an average density on available sequence of one SNP every 1.9kilobases. These SNPs were primarily discovered by two projects: The SNP Consortium and the analysis of clone overlaps by the International Human Genome Sequencing Consortium. The map integrates all publicly available ...
Journal: Nature , vol. 409, no. 6822, pp. 928-933, 2001 Sridhar Ramaswamy, Pablo Tamayo, Ryan Rifkin, Sayan Mukherjee, Chen-Hsiang Yeang, Michael Angelo, Christine Ladd,Michael Reich, Eva Latulippe, Jill P. Mesirov, Tomaso Poggio, William GeraldEric S. Lander Richard A. Gibbs, John W. Belmont, Paul Hardenbol, Thomas D. Willis, Fuli Yu, Huanming Yang, Lan-Yang Ch'ang, Wei Huang, Bin Liu, Yan Shen, Paul Kwong-Hang Tam, Lap-Chee TsuiEric S. Lander The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the ...
Journal: Nature , vol. 426, no. 6968, pp. 789-796, 2003 Ewan Birney, John A. Stamatoyannopoulos, Anindya Dutta, Roderic Guigó, Thomas R. Gingeras, Elliott H. Margulies,Zhiping Weng, Michael Snyder, Emmanouil T. Dermitzakis, Robert E. Thurman, Michael S. Kuehn, Christopher M. TaylorEric S. Lander We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in ...
Journal: Nature , vol. 447, no. 7146, pp. 799-816, 2007 Linkage disequilibrium (LD) analysis is traditionally based on individual genetic markers and often yields an erratic, non- monotonic picture, because the power to detect allelic associa- tions depends on specific properties of each marker, such as frequency and population history. Ideally, LD analysis should be based directly on the underlying haplotype structure of the human genome, but this structure has ...
Dinesh Singh, Phillip G. Febbo, Kenneth Ross, Donald G. Jackson, Judith Manola, Christine Ladd, Pablo Tamayo, Andrew A. Renshaw, Anthony V. D'Amico, Jerome P. Richie, Eric S. Lander, Massimo Loda Prostate tumors are among the most heterogeneous of cancers, both histologically and clinically. Microarray expression analysis was used to determine whether global biological differences underlie common pathological features of prostate cancer and to identify genes that might anticipate the clinical behavior of this disease. While no expression correlates of age, serum prostate specific antigen (PSA), and measures of local invasion ...
Journal: Cancer Cell , vol. 1, no. 2, pp. 203-209, 2002 Acute lymphoblastic leukemias carrying a chromosomal translocation involving the mixed-lineage leukemia gene (MLL, ALL1, HRX) have a particularly poor prognosis. Here we show that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes. Clustering algorithms reveal that lymphoblastic leukemias with MLL translocations can ...
Tarjei S. Mikkelsen, Manching Ku, David B. Jaffe, Biju Issac, Erez Lieberman, Georgia Giannoukos, Pablo Alvarez, William Brockman, Tae-Kyung Kim, Richard P. Koche, William Lee, Eric MendenhallEric S. Lander We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively ...
Journal: Nature , vol. 448, no. 7153, pp. 553-560, 2007 Comprehensive identification of all functional elements encoded in the human genome is a fundamental need in biomedical research. Here, we present a comparative analysis of the human, mouse, rat and dog genomes to create a systematic catalogue of common regulatory motifs in promoters and 3' untranslated regions (3' UTRs). The promoter analysis yields 174 candidate motifs, including most previously known ...
Journal: Nature , vol. 434, no. 7031, pp. 338-345, 2005 Olivier Jaillon, Jean-Marc Aury, Frédéric Brunet, Jean-Louis Petit, Nicole Stange-Thomann, Evan Mauceli, Laurence Bouneau, Cécile Fischer, Catherine Ozouf-Costaz, Alain Bernot, Sophie Nicaud, David JaffeEric S. Lander Tetraodon nigroviridis is a freshwater puffer fish with the smallest known vertebrate genome. Here, we report a draft genome sequence with long-range linkage and substantial anchoring to the 21 Tetraodon chromosomes. Genome analysis provides a greatly improved fish gene catalogue, including identifying key genes previously thought to be absent in fish. Comparison with other vertebrates and a urochordate indicates ...
Journal: Nature , vol. 431, no. 7011, pp. 946-957, 2004 David E. Reich, Michele Cargill, Stacey Bolk, James Ireland, Pardis C. Sabeti, Daniel J. Richter, Thomas Lavery, Rose Kouyoumjian, Shelli F. Farhadian, Ryk Ward, Eric S. Lander With the availability of a dense genome-wide map of single nucleotide polymorphisms (SNPs), a central issue in human genetics is whether it is now possible to use linkage disequilibrium (LD) to map genes that cause disease. LD refers to correlations among neighbouring alleles, reflecting `haplotypes' descended from single, ancestral chromosomes. The size of LD blocks has been the subject ...
Journal: Nature , vol. 411, pp. 199-204, 2001 Eric S. Lander, Philip Green Human genetic linkage maps are most accurately constructed by using information from many loci simultaneously. Traditional methods for such multilocus linkage analysis are computationally prohibitive in general, even with supercomputers. The problem has acquired practical importance because of the current international collaboration aimed at constructing a complete human linkage map of DNA markers through the study of three-generation pedigrees. ...
Kerstin Lindblad-Toh, Claire M. Wade, Tarjei S. Mikkelsen, Elinor K. Karlsson, David B. Jaffe, Michael Kamal, Michele Clamp, Jean L. Chang, Edward J. Kulbokas, Michael C. Zody, Evan Mauceli, Xiaohui XieEric S. Lander Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate ...
Journal: Nature , vol. 438, no. 7069, pp. 803-819, 2005 James E. Galagan, Sarah E. Calvo, Katherine A. Borkovich, Eric U. Selker, Nick D. Read, David Jaffe, William FitzHugh, Li-Jun Ma, Serge Smirnov, Seth Purcell, Bushra Rehman, Timothy ElkinsEric S. Lander Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes-more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than ...
Journal: Nature , vol. 422, no. 6934, pp. 859-868, 2003 Whole-genome duplication followed by massive gene loss and specialization has long been postulated as a powerful mechanism of evolutionary innovation. Recently, it has become possible to test this notion by searching complete genome sequence for signs of ancient duplication. Here, we show that the yeast Saccharomyces cerevisiae arose from ancient whole-genome duplication, by sequencing and analysing Kluyveromyces waltii, ...
Journal: Nature , vol. 428, no. 6983, pp. 617-624, 2004 Comprehensive identification of all functional elements encoded in the human genome is a fundamental need in biomedical research. Here, we present a comparative analysis of the human, mouse, rat and dog genomes to create a systematic catalogue of common regulatory motifs in promoters and 3 0 untranslated regions (3 0 UTRs). The promoter analysis yields 174 candidate motifs, including most ...
Journal: Nature , vol. 335, no. 6192, pp. 721-726, 1988 Aravind Subramanian, Pablo Tamayo, Vamsi K. Mootha, Sayan Mukherjee, Benjamin L. Ebert, Michael A. Gillette, Amanda Paulovich, Scott L. Pomeroy, Todd R. Golub, Eric S. Lander, Jill P. Mesirov Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological ...
Arindam Bhattacharjee, William G. Richards, Jane Staunton, Cheng Li, Stefano Monti, Priya Vasa, Christine Ladd, Javad Beheshti, Raphael Bueno, Michael Gillette, Massimo Loda, Griffin WeberEric S. Lander Bradley E. Bernstein, Michael Kamal, Kerstin Lindblad-Toh, Stefan Bekiranov, Dione K. Bailey, Dana J. Huebert, Scott McMahon, Elinor K. Karlsson, Edward J. Kulbokas III, Thomas R. Gingeras, Stuart L. Schreiber, Eric S. Lander We mapped histone H3 lysine 4 di- and trimethylation and lysine 9/14 acetylation across the nonrepetitive portions of human chromosomes 21 and 22 and compared patterns of lysine 4 dimethylation for several orthologous human and mouse loci. Both chromosomes show punctate sites enriched for modified histones. Sites showing trimethylation correlate with transcription starts, while those showing mainly dimethylation occur ...
Journal: Cell , vol. 120, no. 2, pp. 169-181, 2005 Pardis C. Sabeti, David E. Reich, John M. Higgins, Haninah Z. P. Levine, Daniel J. Richter, Stephen F. Schaffner, Stacey B. Gabriel, Jill V. Platko, Nick J. Patterson, Gavin J. McDonald, Hans C. Ackerman, Sarah J. CampbellEric S. Lander The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess ...
Journal: Nature , vol. 419, no. 6909, pp. 832-837, 2002 We used genome-wide expression analysis to explore how gene expression in Saccharomyces cerevisiae is remodeled in response to various changes in extracellular environment, including changes in temperature, oxidation, nutrients, pH, and osmolarity. The results demonstrate that more than half of the genome is involved in various responses to environmental change and identify the global set of genes induced and ...
Published in 2001.
G. D. Schuler, M. S. Boguski, E. A. Stewart, L. D. Stein, G. Gyapay, K. Rice, R. E. White, P. Rodriguez-Tome, A. Aggarwal, E. Bajorek, S. Bentolila, B. B. BirrenE. S. Lander The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than ...
Journal: Science , vol. 274, no. 5287, pp. 540-546, 1996 E. S. Lander
Journal: Science , vol. 274, no. 5287, pp. 536-539, 1996 Y. Okazaki, M. Furuno, T. Kasukawa, J. Adachi, H. Bono, S. Kondo, I. Nikaido, N. Osato, R. Saito, H. Suzuki, I. Yamanaka, H. KiyosawaE. S. Lander Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These ...
Journal: Nature , vol. 420, no. 6915, pp. 563-573, 2002 William F. Dietrich, Joyce Miller, Robert Steen, Mark A. Merchant, Deborah Damron-Boles, Zeeshan Husain, Robert Dredge,Mark J. Daly, Kimberly A. Ingalls, Cheryl A. Evans, Margaret M. Deangelis, Leonid KruglyakEric S. Lander THE availability of dense genetic linkage maps of mammalian genomes makes feasible a wide range of studies, including positional cloning of monogenic traits, genetic dissection of polygenic traits, construction of genome-wide physical maps, rapid marker-assisted construction of congenic strains, and evolutionary comparisons1,2. We have been engaged for the past five years in a concerted effort to produce ...
Journal: Nature , vol. 380, no. 6570, pp. 149-152, 1996 David E. Reich, Eric S. Lander Human disease genes show enormous variation in their allelic spectra; that is, in the number and population frequency of the disease-predisposing alleles at the loci. For some genes, there are a few predominant disease alleles. For others, there is a wide range of disease alleles, each relatively rare. The allelic spectrum is important: disease genes with only a few ...
Dendritic cells are involved in the initiation of both innate and adaptive immunity. To systematically explore how dendritic cells modulate the immune system in response to different pathogens, we used oligonucleotide microarrays to measure gene expression profiles of dendritic cells in response to Escherichia coli, Candida albicans, and influenza virus as well as to their molecular components. Both a shared ...
Journal: Science , vol. 294, no. 5543, pp. 870-875, 2001 Thomas J. Hudson, Lincoln D. Stein, Sebastian S. Gerety, Junli Ma, Andrew B. Castle, James Silva, Donna K. Slonim,Rafael Baptista, Leonid Kruglyak, Shu-Hua Xu, Xintong Hu, Angela M. E. ColbertEric S. Lander A physical map has been constructed of the human genome containing 15,086 sequence- tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results ...
Journal: Science , vol. 270, no. 5244, pp. 1945-1954, 1995 L. Kruglyak, E. S. Lander Sib-pair analysis is an increasingly important tool for genetic dissection of complex traits. Current methods for sib-pair analysis are primarily based on studying individual genetic markers one at a time and thus fail to use the full inheritance information provided by multipoint linkage analysis. In this paper, we describe how to extract the complete multipoint inheritance information for ...
modulateschromatin structure and genome function. The epigenome refers to the complete description of these potentially heritable changes across the genome. The composition of the epigenome within a given cell is a function of genetic determinants,lineage, and environ- ment. With the sequencing of the human genome completed, investigators now seek a comprehensive view of the epigenetic changes that determine how ...
Journal: Cell , vol. 128, no. 4, pp. 669-681, 2007 Justin Lamb, Emily D. Crawford, David Peck, Joshua W. Modell, Irene C. Blat, Matthew J. Wrobel, Jim Lerner, Jean-Philippe Brunet, Aravind Subramanian, Kenneth N. Ross, Michael Reich, Haley HieronymusEric S. Lander To pursue a systematic approach to the discovery of functional connections among diseases, genetic perturbation, and drug action, we have created the first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules, together with pattern-matching software to mine these data. We demonstrate that this ``Connectivity Map'' resource can be used ...
Journal: Science , vol. 313, no. 5795, pp. 1929-1935, 2006 Andrew G. Clark, Michael B. Eisen, Douglas R. Smith, Brian Oliver, Therese A. Markow, Thomas C. Kaufman, Manolis Kellis, William Gelbart, Venky N. Iyer, Daniel A. Pollard, Timothy B. Sackton, Amanda M. LarracuenteEric Lander Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns ...
Journal: Nature , vol. 450, no. 7167, pp. 203-218, 2007 Adolfo A. Ferrando, Donna S. Neuberg, Jane Staunton, Mignon L. Loh, Christine Huard, Susana C. Raimondi, Fred G. Behm, Ching-Hon Pui, James R. Downing, D. Gary Gilliland, Eric S. Lander, Todd R. Golub Human T cell leukemias can arise from oncogenes activated by specific chromosomal translocations involving the T cell receptor genes. Here we show that five different T cell oncogenes (HOX11, TAL1, LYL1, LMO1, and LMO2) are often aberrantly expressed in the absence of chromosomal abnormalities. Using oligonucleotide microarrays, we identified several gene expression signatures that were indicative of leukemic arrest at ...
Journal: Nature , vol. 440, no. 7086, pp. 944-948, 2006 P. Deloukas, G. D. Schuler, G. Gyapay, E. M. Beasley, C. Soderlund, P. Rodriguez-Tome, L. Hui, T. C. Matise, K. B. McKusick, J. S. Beckmann, S. Bentolila, M.-T. BihoreauE. S. Lander Journal: Science , vol. 282, no. 5389, pp. 744-746, 1998 Ken N. Ross, Pablo Tamayo, Andrew P. Weng, Jeffery L. Kutok, Ricardo C. T. Aguiar, Michelle Gaasenbeek, Michael Angelo, Michael Reich, Geraldine S. Pinkus, Tane S. Ray, Margaret A. Koval, Kim W. LastEric S. Lander Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable in less than 50% of patients. Prognostic models based on pre-treatment characteristics, such as the International Prognostic Index (IPI), are currently used to predict outcome in DLBCL. However, clinical outcome models identify neither the molecular basis of clinical heterogeneity, nor specific therapeutic targets. We ...
Eric S. Lander, David Botstein An efficient strategy for mapping human genes that cause recessive traits has been devised that uses mapped restriction fragment length polymorphisms (RFLPs) and the DNA of affected children from consanguineous marriages. The method involves detection of the disease locus by virtue of the fact that the adjacent region will preferentially be homozygous by descent in such inbred children. A single ...
Journal: Science , vol. 236, no. 4808, pp. 1567-1570, 1987 Kerstin Lindblad, Katie Miller, Sheila Guschwan, Edward J. Kulbokas, Sinead O'Leary, Ellen Winchester, Ken Dewar, Todd Green, Valerie Stone, Christine Chow, Albert Cohen, Diane LangelierEric S. Lander Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease1. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring suscepti- bility to Crohn disease. The key issues are: (i) to detect a ...
Matthew L Freedman, Andre A Mignault, Nick Patterson, Stacey B Gabriel, Eric J Topol, Jordan W Smoller, Carlos N Pato,Michele T Pato, Tracey L Petryshen, Laurence N Kolonel, Eric S Lander, Pamela Sklar David A. Hafler, Alastair Compston, Stephen Sawcer, Eric S. Lander, Mark J. Daly, Philip L. De Jager, Paul I. W. de Bakker, Stacey B. Gabriel, Daniel B. Mirel, Adrian J. Ivinson, Margaret A. Pericak-Vance, Simon G. Gregory Background Multiple sclerosis has a clinically significant heritable component. We conducted a ge- nomewide association study to identify alleles associated with the risk of multiple sclerosis. Methods We used DNA microarray technology to identify common DNA sequence variants in 931 family trios (consisting of an affected child and both parents) and tested them for association. For replication, we genotyped another ...
Published in 2010.
William F. Dietrich, Joyce C. Miller, Robert G. Steen, Mark Merchant, Deborah Damron, Robert Nahf, Alec Gross, Diane C. Joyce, Michael Wessel, Robert D. Dredge, Andre Marquis, Lincoln D. SteinEric S. Lander Jason Moffat, Dorre A. Grueneberg, Xiaoping Yang, So Young Kim, Angela M. Kloepfer, Gregory Hinkle, Bruno Piqani,Thomas M. Eisenhaure, Biao Luo, Jennifer K. Grenier, Anne E. Carpenter, Shi Yin FooEric S. Lander Journal: Cell , vol. 124, no. 6, pp. 1283-1298, 2006 Alexander Meissner, Tarjei S. Mikkelsen, Hongcang Gu, Marius Wernig, Jacob Hanna, Andrey Sivachenko, Xiaolan Zhang,Bradley E. Bernstein, Chad Nusbaum, David B. Jaffe, Andreas Gnirke, Rudolf JaenischEric S. Lander DNA methylation is essential for normal development and has been implicated in many pathologies including cancer. Our knowledge about the genome-wide distribution of DNA methylation, how it changes during cellular differentiation and how it relates to histone methylation and other chromatin modifications in mammals remains limited. Here we report the generation and analysis of genome-scale DNA methylation profiles ...
Journal: Nature , vol. 454, no. 7205, pp. 766-770, 2008 Eric S. Lander, Bob Crimi The use of molecular markers to identify quantitative trait loci (QTLs) affecting agriculturally important traits has become a key approach in plant genetics-both for understanding the genetic basis of these traits and to help design novel plant improvement programs. In the study reported here, we mapped QTLs (and evaluated their phenotypic effects) associated with seven major traits (including grain ...
Journal: Science , vol. 285, no. 5425, pp. 251-254, 1999