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  • 1
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    Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-06-06
    Description: Single-nucleotide polymorphisms (SNPs) are the most frequent type of variation in the human genome, and they provide powerful tools for a variety of medical genetic studies. In a large-scale survey for SNPs, 2.3 megabases of human genomic DNA was examined by a combination of gel-based sequencing and high-density variation-detection DNA chips. A total of 3241 candidate SNPs were identified. A genetic map was constructed showing the location of 2227 of these SNPs. Prototype genotyping chips were developed that allow simultaneous genotyping of 500 SNPs. The results provide a characterization of human diversity at the nucleotide level and demonstrate the feasibility of large-scale identification of human SNPs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, D G -- Fan, J B -- Siao, C J -- Berno, A -- Young, P -- Sapolsky, R -- Ghandour, G -- Perkins, N -- Winchester, E -- Spencer, J -- Kruglyak, L -- Stein, L -- Hsie, L -- Topaloglou, T -- Hubbell, E -- Robinson, E -- Mittmann, M -- Morris, M S -- Shen, N -- Kilburn, D -- Rioux, J -- Nusbaum, C -- Rozen, S -- Hudson, T J -- Lipshutz, R -- Chee, M -- Lander, E S -- HG00098/HG/NHGRI NIH HHS/ -- HG01323/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 1998 May 15;280(5366):1077-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9582121" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Alleles ; Chromosome Mapping/*methods ; DNA, Complementary ; Databases, Factual ; Deoxyribonucleotides/*genetics ; Dinucleoside Phosphates ; Gene Expression ; Genetic Markers ; *Genetic Techniques ; Genetic Variation ; *Genome, Human ; *Genotype ; Heterozygote ; Homozygote ; Humans ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Reproducibility of Results ; Sequence Analysis, DNA ; Sequence Tagged Sites
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Comprehensive polymorphism survey elucidates population structure of Saccharomyces cerevisiae (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-02-13
    Description: Comprehensive identification of polymorphisms among individuals within a species is essential both for studying the genetic basis of phenotypic differences and for elucidating the evolutionary history of the species. Large-scale polymorphism surveys have recently been reported for human, mouse and Arabidopsis thaliana. Here we report a nucleotide-level survey of genomic variation in a diverse collection of 63 Saccharomyces cerevisiae strains sampled from different ecological niches (beer, bread, vineyards, immunocompromised individuals, various fermentations and nature) and from locations on different continents. We hybridized genomic DNA from each strain to whole-genome tiling microarrays and detected 1.89 million single nucleotide polymorphisms, which were grouped into 101,343 distinct segregating sites. We also identified 3,985 deletion events of length 〉200 base pairs among the surveyed strains. We analysed the genome-wide patterns of nucleotide polymorphism and deletion variants, and measured the extent of linkage disequilibrium in S. cerevisiae. These results and the polymorphism resource we have generated lay the foundation for genome-wide association studies in yeast. We also examined the population structure of S. cerevisiae, providing support for multiple domestication events as well as insight into the origins of pathogenic strains.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782482/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782482/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schacherer, Joseph -- Shapiro, Joshua A -- Ruderfer, Douglas M -- Kruglyak, Leonid -- GM071508/GM/NIGMS NIH HHS/ -- P50 GM071508-059001/GM/NIGMS NIH HHS/ -- P50 GM071508-059002/GM/NIGMS NIH HHS/ -- R37 MH059520/MH/NIMH NIH HHS/ -- R37 MH059520-12/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Mar 19;458(7236):342-5. doi: 10.1038/nature07670. Epub 2009 Feb 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lewis-Sigler Institute for Integrative Genomics, Department of Ecology and Evolutionary Biology and Howard Hughes Medical Institute, Princeton University, Princeton, New Jersey 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19212320" target="_blank"〉PubMed〈/a〉
    Keywords: Ecosystem ; Genetics, Population ; *Genomics ; Humans ; Linkage Disequilibrium/genetics ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/*genetics ; Saccharomyces cerevisiae/*classification/*genetics/isolation & purification
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Finding the missing heritability of complex diseases (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-10-09
    Description: Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831613/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831613/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Manolio, Teri A -- Collins, Francis S -- Cox, Nancy J -- Goldstein, David B -- Hindorff, Lucia A -- Hunter, David J -- McCarthy, Mark I -- Ramos, Erin M -- Cardon, Lon R -- Chakravarti, Aravinda -- Cho, Judy H -- Guttmacher, Alan E -- Kong, Augustine -- Kruglyak, Leonid -- Mardis, Elaine -- Rotimi, Charles N -- Slatkin, Montgomery -- Valle, David -- Whittemore, Alice S -- Boehnke, Michael -- Clark, Andrew G -- Eichler, Evan E -- Gibson, Greg -- Haines, Jonathan L -- Mackay, Trudy F C -- McCarroll, Steven A -- Visscher, Peter M -- P50 GM065509/GM/NIGMS NIH HHS/ -- P50 GM065509-080006/GM/NIGMS NIH HHS/ -- R01 HG003229/HG/NHGRI NIH HHS/ -- R01 HL072904/HL/NHLBI NIH HHS/ -- R01 HL072904-07/HL/NHLBI NIH HHS/ -- R01 MH084695/MH/NIMH NIH HHS/ -- U01 HL084706/HL/NHLBI NIH HHS/ -- UL1 RR024992/RR/NCRR NIH HHS/ -- England -- Nature. 2009 Oct 8;461(7265):747-53. doi: 10.1038/nature08494.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Human Genome Research Institute, Building 31, Room 4B09, 31 Center Drive, MSC 2152, Bethesda, Maryland 20892-2152, USA. manoliot@mail.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19812666" target="_blank"〉PubMed〈/a〉
    Keywords: Genetic Diseases, Inborn/*genetics ; Genetic Predisposition to Disease/*genetics ; Genetics, Medical/*methods/trends ; Genome-Wide Association Study/methods/trends ; Humans ; Inheritance Patterns/genetics ; Pedigree
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Genetics. It's the sequence, stupid! (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-10-18
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765165/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765165/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coller, Hilary A -- Kruglyak, Leonid -- R01 GM081686/GM/NIGMS NIH HHS/ -- R01 GM086465/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Oct 17;322(5900):380-1. doi: 10.1126/science.1165664.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. hcoller@princeton.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18927376" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Human, Pair 21/*genetics/metabolism ; Disease Models, Animal ; Down Syndrome/genetics ; *Gene Expression Regulation ; Hepatocytes/*metabolism ; Histones/metabolism ; Humans ; Mice ; RNA, Messenger/genetics/metabolism ; *Regulatory Sequences, Nucleic Acid ; Species Specificity ; Transcription Factors/metabolism ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    Genetic loci affecting resistance to human malaria parasites in a West African mosquito vector population (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-10-05
    Description: Successful propagation of the malaria parasite Plasmodium falciparum within a susceptible mosquito vector is a prerequisite for the transmission of malaria. A field-based genetic analysis of the major human malaria vector, Anopheles gambiae, has revealed natural factors that reduce the transmission of P. falciparum. Differences in P. falciparum oocyst numbers between mosquito isofemale families fed on the same infected blood indicated a large genetic component affecting resistance to the parasite, and genome-wide scanning in pedigrees of wild mosquitoes detected segregating resistance alleles. The apparently high natural frequency of resistance alleles suggests that malaria parasites (or a similar pathogen) exert a significant selective pressure on vector populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Niare, Oumou -- Markianos, Kyriacos -- Volz, Jennifer -- Oduol, Frederick -- Toure, Abdoulaye -- Bagayoko, Magaran -- Sangare, Djibril -- Traore, Sekou F -- Wang, Rui -- Blass, Claudia -- Dolo, Guimogo -- Bouare, Madama -- Kafatos, Fotis C -- Kruglyak, Leonid -- Toure, Yeya T -- Vernick, Kenneth D -- New York, N.Y. -- Science. 2002 Oct 4;298(5591):213-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical and Molecular Parasitology, New York University School of Medicine, 341 East 25th Street, New York, NY 10010, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12364806" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Anopheles/*genetics/immunology/*parasitology/physiology ; Chromosome Mapping ; Female ; *Genes, Insect ; Genetic Linkage ; Genetic Markers ; Genome ; Genotype ; Host-Parasite Interactions ; Humans ; Insect Vectors/genetics/immunology/*parasitology/physiology ; Karyotyping ; Malaria, Falciparum/transmission ; Male ; Mali ; Oviposition ; Phenotype ; Plasmodium falciparum/pathogenicity/*physiology ; Virulence
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Finding the sources of missing heritability in a yeast cross (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-02-05
    Description: For many traits, including susceptibility to common diseases in humans, causal loci uncovered by genetic-mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this 'missing heritability' have been proposed. Here we use a large cross between two yeast strains to accurately estimate different sources of heritable variation for 46 quantitative traits, and to detect underlying loci with high statistical power. We find that the detected loci explain nearly the entire additive contribution to heritable variation for the traits studied. We also show that the contribution to heritability of gene-gene interactions varies among traits, from near zero to approximately 50 per cent. Detected two-locus interactions explain only a minority of this contribution. These results substantially advance our understanding of the missing heritability problem and have important implications for future studies of complex and quantitative traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001867/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001867/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bloom, Joshua S -- Ehrenreich, Ian M -- Loo, Wesley T -- Lite, Thuy-Lan Vo -- Kruglyak, Leonid -- F32 HG005176/HG/NHGRI NIH HHS/ -- F32 HG51762/HG/NHGRI NIH HHS/ -- P50 GM071508/GM/NIGMS NIH HHS/ -- R01 GM102308/GM/NIGMS NIH HHS/ -- R37 MH59520/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Feb 14;494(7436):234-7. doi: 10.1038/nature11867. Epub 2013 Feb 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23376951" target="_blank"〉PubMed〈/a〉
    Keywords: *Crosses, Genetic ; Humans ; *Models, Genetic ; Phenotype ; Quantitative Trait Loci/*genetics ; *Quantitative Trait, Heritable ; Saccharomyces cerevisiae/*genetics/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
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    An STS-based map of the human genome (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-12-22
    Description: 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 of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hudson, T J -- Stein, L D -- Gerety, S S -- Ma, J -- Castle, A B -- Silva, J -- Slonim, D K -- Baptista, R -- Kruglyak, L -- Xu, S H -- Hu, X -- Colbert, A M -- Rosenberg, C -- Reeve-Daly, M P -- Rozen, S -- Hui, L -- Wu, X -- Vestergaard, C -- Wilson, K M -- Bae, J S -- Maitra, S -- Ganiatsas, S -- Evans, C A -- DeAngelis, M M -- Ingalls, K A -- Nahf, R W -- Horton, L T Jr -- Anderson, M O -- Collymore, A J -- Ye, W -- Kouyoumjian, V -- Zemsteva, I S -- Tam, J -- Devine, R -- Courtney, D F -- Renaud, M T -- Nguyen, H -- O'Connor, T J -- Fizames, C -- Faure, S -- Gyapay, G -- Dib, C -- Morissette, J -- Orlin, J B -- Birren, B W -- Goodman, N -- Weissenbach, J -- Hawkins, T L -- Foote, S -- Page, D C -- Lander, E S -- HG00017/HG/NHGRI NIH HHS/ -- HG00098/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 1995 Dec 22;270(5244):1945-54.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead-MIT Center for Genome Research, Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8533086" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Chromosome Mapping ; Chromosomes, Artificial, Yeast ; Databases, Factual ; Gene Expression ; Genetic Markers ; *Genome, Human ; *Human Genome Project ; Humans ; Hybrid Cells ; Polymerase Chain Reaction ; *Sequence Analysis, DNA ; *Sequence Tagged Sites
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Natural malaria infection in Anopheles gambiae is regulated by a single genomic control region (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-04-29
    Description: We surveyed an Anopheles gambiae population in a West African malaria transmission zone for naturally occurring genetic loci that control mosquito infection with the human malaria parasite, Plasmodium falciparum. The strongest Plasmodium resistance loci cluster in a small region of chromosome 2L and each locus explains at least 89% of parasite-free mosquitoes in independent pedigrees. Together, the clustered loci form a genomic Plasmodium-resistance island that explains most of the genetic variation for malaria parasite infection of mosquitoes in nature. Among the candidate genes in this chromosome region, RNA interference knockdown assays confirm a role in Plasmodium resistance for Anopheles Plasmodium-responsive leucine-rich repeat 1 (APL1), encoding a leucine-rich repeat protein that is similar to molecules involved in natural pathogen resistance mechanisms in plants and mammals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Riehle, Michelle M -- Markianos, Kyriacos -- Niare, Oumou -- Xu, Jiannong -- Li, Jun -- Toure, Abdoulaye M -- Podiougou, Belco -- Oduol, Frederick -- Diawara, Sory -- Diallo, Mouctar -- Coulibaly, Boubacar -- Ouatara, Ahmed -- Kruglyak, Leonid -- Traore, Sekou F -- Vernick, Kenneth D -- New York, N.Y. -- Science. 2006 Apr 28;312(5773):577-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Microbial and Plant Genomics and Department of Microbiology, University of Minnesota, St. Paul, MN 55108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16645095" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Anopheles gambiae/*genetics/immunology/*parasitology ; Chromosome Mapping ; Female ; *Genes, Insect ; Genetic Linkage ; Genetic Variation ; Genome, Insect ; Humans ; Immunity, Innate/genetics ; Insect Proteins/*genetics/physiology ; Insect Vectors/genetics/*parasitology ; Malaria, Falciparum/parasitology ; Male ; Mali ; Oligonucleotide Array Sequence Analysis ; Pedigree ; Phenotype ; Plasmodium berghei/immunology/pathogenicity ; Plasmodium falciparum/immunology/*pathogenicity ; RNA Interference
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    Evolution. An embarrassment of switches (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-08-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kruglyak, Leonid -- Stern, David L -- New York, N.Y. -- Science. 2007 Aug 10;317(5839):758-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. leonid@genomics.princeton.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17690280" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Chromatin Immunoprecipitation ; *Evolution, Molecular ; Gene Expression Regulation ; Humans ; *Mutation ; Oligonucleotide Array Sequence Analysis ; Phenotype ; *Regulatory Sequences, Nucleic Acid ; Species Specificity ; Transcription Factors/*metabolism ; Yeasts/*genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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