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  • 1.
    Mikkelsen, Tarjei
    et al.
    Broad Institute.
    Hillier, LaDeana
    Washington University School of Medicine, Genome Sequencing Center.
    Eichler, Evan
    University of Washington, Department of Genome Sciences.
    Zody, Michael
    Broad Institute.
    Jaffe, David
    Broad Institute.
    Yang, Shiaw-Pyng
    Washington University School of Medicine, Genome Sequencing Center.
    Enard, Wolfgang
    Max Planck Institute of Evolutionary Anthropology.
    Hellmann, Ines
    Max Planck Institute of Evolutionary Anthropology.
    Lindblad-Toh, Kerstin
    Broad Institute.
    Altheide, Tasha
    University of California, San Diego.
    Archidiacono, Nicoletta
    University of Bari, Department of Genetics and Microbiology.
    Bork, Peer
    EMBL.
    Butler, Jonathan
    Broad Institute.
    Chang, Jean
    Broad Institute.
    Cheng, Ze
    University of Washington, Department of Genome Sciences.
    Chinwalla, Asif
    Washington University School of Medicine, Genome Sequencing Center.
    de Jong, Pieter
    Children's Hospital Oakland Research Institute.
    Delehaunty, Kimberley
    Washington University School of Medicine, Genome Sequencing Center.
    Fronick, Catrina
    Washington University School of Medicine, Genome Sequencing Center.
    Fulton, Lucinda
    Washington University School of Medicine, Genome Sequencing Center.
    Gilad, Yoav
    Yale University School of Medicine, Department of Genetics.
    Glusman, Gustavo
    Institute for Systems Biology.
    Gnerre, Sante
    Broad Institute.
    Graves, Tina
    Washington University School of Medicine, Genome Sequencing Center.
    Hayakawa, Toshiyuki
    University of California, San Diego.
    Hayden, Karen
    Case Western Reserve University, Department of Genetics.
    Huang, Xiaoqiu
    Iowa State University, Department of Computer Science.
    Ji, Hongkai
    Harvard University, Department of Statistics.
    Kent, W.
    University of California, Santa Cruz, Center for Biomolecular Science and Engineering.
    King, Mary-Claire
    University of Washington, Department of Genome Sciences.
    Kulbokas, Edward
    Broad Institute.
    Lee, Ming
    University of Washington, Department of Genome Sciences.
    Liu, Ge
    Case Western Reserve University, Department of Genetics.
    Lopez-Otin, Carlos
    Universidad de Oviedo, Instituto Universitario de Oncologia del Principado de Asturias, Departamento de Bioquimica y Biologia Molecular.
    Makova, Kateryna
    The Pennsylvania State University, Center for Comparative Genomics and Bioinformatics and Department of Biology.
    Man, Orna
    Weizmann Institute of Science, Department of Structural Biology.
    Mardis, Elaine
    Washington University School of Medicine, Genome Sequencing Center.
    Mauceli, Evan
    Broad Institute.
    Miner, Tracie
    Washington University School of Medicine, Genome Sequencing Center.
    Nash, illiam
    Washington University School of Medicine, Genome Sequencing Center.
    Nelson, Joanne
    Washington University School of Medicine, Genome Sequencing Center.
    Pääbo, Svante
    Max Planck Institute of Evolutionary Anthropology.
    Patterson, Nick
    Broad Institute.
    Pohl, Craig
    Washington University School of Medicine, Genome Sequencing Center.
    Pollard, Katherine
    University of California, Santa Cruz, Center for Biomolecular Science and Engineering.
    Prüfer, Kay
    Max Planck Institute for Evolutionary Anthropology.
    Puente, Xose
    Universidad de Oviedo, Instituto Universitario de Oncologia del Principado de Asturias, Departamento de Bioquimica y Biologia Molecular.
    Reich, David
    Broad Institute.
    Rocchi, Mariano
    University of Bari, Department of Genetics and Microbiology.
    Rosenbloom, Kate
    University of California, Santa Cruz, Center for Biomolecular Science and Engineering.
    Ruvolo, Maryellen
    Harvard University, Department of Anthropology and of Organismic and Evolutionary Biology.
    Richter, Daniel
    Broad Institute.
    Schaffner, Stephen
    Broad Institute.
    Smit, Arian
    Institute for Systems Biology.
    Smith, Scott
    Washington University School of Medicine, Genome Sequencing Center.
    Suyama, Mikita
    EMBL.
    Taylor, James
    The Pennsylvania State University, Center for Comparative Genomics and Bioinformatics and Department of Biology.
    Torrents, David
    EMBL.
    Tuzun, Eray
    University of Washington, Department of Genome Sciences.
    Varki, Ajit
    University of California, San Diego.
    Velasco, Gloria
    Universidad de Oviedo, Instituto Universitario de Oncologia del Principado de Asturias, Departamento de Bioquimica y Biologia Molecular.
    Ventura, Mario
    University of Bari, Department of Genetics and Microbiology.
    Wallis, John
    Washington University School of Medicine, Genome Sequencing Center.
    Wendl, Michael
    Washington University School of Medicine, Genome Sequencing Center.
    Wilson, Richard
    Washington University School of Medicine, Genome Sequencing Center.
    Lander, Eric
    Broad Institute.
    Waterston, Robert
    University of Washington, Department of Genome Sciences.
    Initial sequence of the chimpanzee genome and comparison with the human genome2005In: Nature, ISSN 0028-0836, Vol. 437, no 7055, 69-87 p.Article in journal (Refereed)
    Abstract [en]

    Here we present a draft genome sequence of the common chimpanzee (Pan troglodytes). Through comparison with the human genome, we have generated a largely complete catalogue of the genetic differences that have accumulated since the human and chimpanzee species diverged from our common ancestor, constituting approximately thirty-five million single-nucleotide changes, five million insertion/deletion events, and various chromosomal rearrangements. We use this catalogue to explore the magnitude and regional variation of mutational forces shaping these two genomes, and the strength of positive and negative selection acting on their genes. In particular, we find that the patterns of evolution in human and chimpanzee protein-coding genes are highly correlated and dominated by the fixation of neutral and slightly deleterious alleles. We also use the chimpanzee genome as an outgroup to investigate human population genetics and identify signatures of selective sweeps in recent human evolution.

  • 2.
    Rubin, Carl-Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Zody, Michael C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Eriksson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Meadows, Jennifer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sherwood, Ellen
    Karolinska Institutet, Department of cell and Molecular Biology.
    Webster, Matthew T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Jiang, Lin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ingman, Max
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sharpe, Ted
    Broad Institute.
    Besnier, Francois
    Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics.
    Ka, Sojeong
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hallböök, Finn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Carlborg, Örjan
    Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics.
    Bed'hom, Bertrand
    INRA, AgroParisTech, Animal Genetics and Integrative Biology.
    Tixier-Boichard, Michèle
    INRA, AgroParisTech, Animal Genetics and Integrative Biology.
    Jensen, Per
    Linköping University, IFM Biology.
    Siegel, Paul
    Virginia Polytechnic Institute and State University, Department of Animal and Poultry Sciences.
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Whole genome resequencing reveals loci under selection during chicken domestication2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, no 7288, 587-591 p.Article in journal (Refereed)
    Abstract [en]

    Domestic animals are excellent models for genetic studies of phenotypic evolution. They have evolved genetic adaptations to a new environment, the farm, and have been subjected to strong human-driven selection leading to remarkable phenotypic changes in morphology, physiology and behaviour. Identifying the genetic changes underlying these developments provides new insight into general mechanisms by which genetic variation shapes phenotypic diversity. Here we describe the use of massively parallel sequencing to identify selective sweeps of favourable alleles and candidate mutations that have had a prominent role in the domestication of chickens (Gallus gallus domesticus) and their subsequent specialization into broiler (meat-producing) and layer (egg-producing) chickens. We have generated 44.5-fold coverage of the chicken genome using pools of genomic DNA representing eight different populations of domestic chickens as well as red jungle fowl (Gallus gallus), the major wild ancestor. We report more than 7,000,000 single nucleotide polymorphisms, almost 1,300 deletions and a number of putative selective sweeps. One of the most striking selective sweeps found in all domestic chickens occurred at the locus for thyroid stimulating hormone receptor (TSHR), which has a pivotal role in metabolic regulation and photoperiod control of reproduction in vertebrates. Several of the selective sweeps detected in broilers overlapped genes associated with growth, appetite and metabolic regulation. We found little evidence that selection for loss-of-function mutations had a prominent role in chicken domestication, but we detected two deletions in coding sequences that we suggest are functionally important. This study has direct application to animal breeding and enhances the importance of the domestic chicken as a model organism for biomedical research.

  • 3.
    Zody, Michael C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Investigation of Mechanics of Mutation and Selection by Comparative Sequencing2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The process of evolution is of both scientific and medical interest. This thesis presents several studies using complete genomic reference sequences, comparative genomic data, and intraspecific diversity data to study the two key processes of evolution: mutation and selection.

    Large duplications, deletions, inversions, and translocations of DNA contribute to genomic variation both between and within species. Human chromosomes 15 and 17 contain a high percentage of dispersed, recently duplicated sequences. Examination of the relationships between these sequences showed that the majority of all duplications within each chromosome could be linked through core sequences that are prone to duplication. Comparison to orthologous sequences in other mammals allowed a reconstruction of the ancestral state of the human chromosomes, revealing that regions of rearrangement specific to the human lineage are highly enriched in chromosome-specific duplications. Comparison to copy number variation data from other studies also shows that these regions are enriched in current human structural variation. One specific region, the MAPT locus at 17q21.31, known to contain an inversion polymorphism in Europeans, was resequenced completely across both human orientation haplotypes and in chimpanzee and orangutan, revealing complex duplication structures at the inversion breakpoints, with the human region being more complex than chimpanzee or orangutan. Fluorescent in-situ hybridization analysis of human, chimpanzee, and orangutan chromosomes showed inversion polymorphisms of independent origin in all three species, demonstrating that this region has been a hotspot of genomic rearrangement for at least twelve million years. These results reveal a mechanistic relationship between sequence duplication and rearrangement in the great apes.

    We also generated a draft sequence of the chimpanzee genome and compared it to that of the human. Among other findings, this showed that CpG dinucleotides contribute 25% of all single base mutations, with a rate of mutation ~10-fold that of other bases, and that the male mutation rate in great apes is ~5-6 times the female rate, a higher ratio than had been observed in comparisons of primates and rodents. We detected six regions of probable recent positive selection in humans with a statistical method relying on chimpanzee sequence to control for regional variation in mutation rates.

    Finally, resequencing of several lines of domestic chicken and comparison to the reference chicken genome identified a number of gene deletions fixed in domestic lines and also several potential selective sweeps. Of particular interest are a missense mutation in TSHR nearly fixed in all domestic chickens and a partial deletion of SH3RF2 fixed in a high growth line. The TSHR mutation may play a role in relaxation of seasonal reproduction. A high-resolution QTL mapping experiment showed that the SH3RF2 deletion is significantly associated with increased growth.

    This work provides important new insights into the mechanics of evolutionary change at both the single nucleotide and structural level and identifies potential targets of natural and artificial selection in humans and chickens.

  • 4.
    Zody, Michael
    et al.
    Broad Institute.
    Garber, Manuel
    Broad Institute.
    Adams, David
    The Wellcome Trust Sanger Institute.
    Sharpe, Ted
    Broad Institute.
    Harrow, Jennifer
    The Wellcome Trust Sanger Institute.
    Lupski, James
    Baylor College of Medicine, Department of Molecular and Human Genetics.
    Nicholson, Christine
    The Wellcome Trust Sanger Institute.
    Searle, Steven
    The Wellcome Trust Sanger Institute.
    Wilming, Laurens
    The Wellcome Trust Sanger Institute.
    Young, Sarah
    Broad Institute.
    Abouelleil, Amr
    Broad Institute.
    Allen, Nicole
    Broad Institute.
    Bi, Weimin
    Baylor College of Medicine, Department of Molecular and Human Genetics.
    Bloom, Toby
    Broad Institute.
    Borowsky, Mark
    Broad Institute.
    Bugalter, Boris
    Broad Institute.
    Butler, Jonathan
    Broad Institute.
    Chang, Jean
    Broad Institute.
    Chen, Chao-Kung
    The Wellcome Trust Sanger Institute.
    Cook, April
    Broad Institute.
    Corum, Benjamin
    Broad Institute.
    Cuomo, Christina
    Broad Institute.
    de Jong, Pieter
    Children's Hospital Oakland Research Institute.
    DeCaprio, David
    Broad Institute.
    Dewar, Ken
    Broad Institute.
    FitzGerald, Michael
    Broad Institute.
    Gilbert, James
    The Wellcome Trust Sanger Institute.
    Gibson, Richard
    The Wellcome Trust Sanger Institute.
    Gnerre, Sante
    Broad Institute.
    Goldstein, Steven
    University of Wisconsin-Madison, Laboratory for Molecular and Computational Genomics.
    Grafham, Darren
    The Wellcome Trust Sanger Institute.
    Grocock, Russell
    The Wellcome Trust Sanger Institute.
    Hafez, Nabil
    Broad Institute.
    Hagopian, Daniel
    Broad Institute.
    Hart, Elizabeth
    The Wellcome Trust Sanger Institute.
    Hosage Norman, Catherine
    Broad Institute.
    Humphray, Sean
    The Wellcome Trust Sanger Institute.
    Jaffe, David
    Broad Institute.
    Jones, Matt
    The Wellcome Trust Sanger Institute.
    Kamal, Michael
    Broad Institute.
    Khodiyan, Varsha
    University College London, Department of Biology.
    LaButti, Kurt
    Broad Institute.
    Laird, Gavin
    The Wellcome Trust Sanger Institute.
    Lehoczky, Jessica
    Broad Institute.
    Liu, Xiaohong
    Broad Institute.
    Lokyitsang, Tashi
    Broad Institute.
    Loveland, Jane
    The Wellcome Trust Sanger Institute.
    Lui, Annie
    Broad Institute.
    Macdonald, Pendexter
    Broad Institute.
    Major, John
    Broad Institute.
    Matthews, Lucy
    The Wellcome Trust Sanger Institute.
    Mauceli, Evan
    Broad Institute.
    McCarroll, Steven
    Broad Institute.
    Mihalev, Atanas
    Broad Institute.
    Mudge, Jonathan
    The Wellcome Trust Sanger Institute.
    Nguyen, Cindy
    Broad Institute.
    Nicol, Robert
    Broad Institute.
    O'Leary, Sinéad
    Broad Institute.
    Osoegawa, Kazutoyo
    Children's Hospital Oakland Research Institute.
    Schwartz, David
    University of Wisconsin-Madison, Laboratory for Molecular and Computational Genomics.
    Shaw-Smith, Charles
    The Wellcome Trust Sanger Institute.
    Stankiewicz, Pawel
    Baylor College of Medicine, Department of Molecular and Human Genetics.
    Steward, Charles
    The Wellcome Trust Sanger Institute.
    Swarbreck, David
    The Wellcome Trust Sanger Institute.
    Venkataraman, Vijay
    Broad Institute.
    Whittaker, Charles
    Broad Institute.
    Yang, Xiaoping
    Broad Institute.
    Zimmer, Andrew
    Broad Institute.
    Bradley, Allan
    The Wellcome Trust Sanger Institute.
    Hubbard, Tim
    The Wellcome Trust Sanger Institute.
    Birren, Bruce
    Broad Institute.
    Rogers, Jane
    The Wellcome Trust Sanger Institute.
    Lander, Eric
    Broad Institute.
    Nusbaum, Chad
    Broad Institute.
    DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage2006In: Nature, ISSN 0028-0836, Vol. 440, no 7087, 1045-1049 p.Article in journal (Refereed)
    Abstract [en]

    Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.

  • 5.
    Zody, Michael
    et al.
    Broad Institute.
    Garber, Manuel
    Broad Institute.
    Sharpe, Ted
    Broad Institute.
    Young, Sarah
    Broad Institute.
    Rowen, Lee
    Institute for Systems Biology.
    O'Neill, Keith
    Broad Institute.
    Whittaker, Charles
    Broad Institute.
    Kamal, Michael
    Broad Institute.
    Chang, Jean
    Broad Institute.
    Cuomo, Christina
    Broad Institute.
    Dewar, Ken
    Broad Institute.
    FitzGerald, Michael
    Broad Institute.
    Kodira, Chinnappa
    Broad Institute.
    Madan, Anup
    Institute for Systems Biology.
    Qin, Shizhen
    Institute for Systems Biology.
    Yang, Xiaoping
    Broad Institute.
    Abbasi, Nissa
    Institute for Systems Biology.
    Abouelleil, Amr
    Broad Institute.
    Arachchi, Harindra
    Broad Institute.
    Baradarani, Lida
    Institute for Systems Biology.
    Birditt, Brian
    Institute for Systems Biology.
    Bloom, Scott
    Institute for Systems Biology.
    Bloom, Toby
    Broad Institute.
    Borowsky, Mark
    Broad Institute.
    Burke, Jeremy
    Institute for Systems Biology.
    Butler, Jonathan
    Broad Institute.
    Cook, April
    Broad Institute.
    DeArellano, Kurt
    Broad Institute.
    DeCaprio, David
    Broad Institute.
    Dorris, Lester
    Broad Institute.
    Dors, Monica
    Institute for Systems Biology.
    Eichler, Evan
    University of Washington, Department of Genome Sciences.
    Engels, Reinhard
    Broad Institute.
    Fahey, Jessica
    Institute for Systems Biology.
    Fleetwood, Peter
    Institute for Systems Biology.
    Friedman, Cynthia
    Fred Hutchinson Cancer Research Center, Division of Human Biology.
    Gearin, Gary
    Broad Institute.
    Hall, Jennifer
    Broad Institute.
    Hensley, Grace
    Institute for Systems Biology.
    Johnson, Ericka
    Institute for Systems Biology.
    Jones, Charlien
    Broad Institute.
    Kamat, Asha
    Broad Institute.
    Kaur, Amardeep
    Institute for Systems Biology.
    Locke, Devin
    University of Washington, Department of Genome Sciences.
    Madan, Anuradha
    Institute for Systems Biology.
    Munson, Glen
    Broad Institute.
    Jaffe, David
    Broad Institute.
    Lui, Annie
    Broad Institute.
    Macdonald, Pendexter
    Broad Institute.
    Mauceli, Evan
    Broad Institute.
    Naylor, Jerome
    Broad Institute.
    Nesbitt, Ryan
    Institute for Systems Biology.
    Nicol, Robert
    Broad Institute.
    O'Leary, Sinéad
    Broad Institute.
    Ratcliffe, Amber
    Institute for Systems Biology.
    Rounsley, Steven
    Broad Institute.
    She, Xinwei
    University of Washington, Department of Genome Sciences.
    Sneddon, Katherine
    University College London, Department of Biology.
    Stewart, Sandra
    Institute for Systems Biology.
    Sougnez, Carrie
    Broad Institute.
    Stone, Sabrina
    Broad Institute.
    Topham, Kerri
    Broad Institute.
    Vincent, Dascena
    Institute for Systems Biology.
    Wang, Shunguang
    Broad Institute.
    Zimmer, Andrew
    Broad Institute.
    Birren, Bruce
    Broad Institute.
    Hood, Leroy
    Institute for Systems Biology.
    Lander, ic
    Broad Institute.
    Nusbaum, Chad
    Broad Institute.
    Analysis of the DNA sequence and duplication history of human chromosome 152006In: Nature, ISSN 0028-0836, Vol. 440, no 7084, 671-675 p.Article in journal (Refereed)
    Abstract [en]

    Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplication in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.

1 - 5 of 5
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