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  • 1
    Publication Date: 2013-08-09
    Description: The HeLa cell line was established in 1951 from cervical cancer cells taken from a patient, Henrietta Lacks. This was the first successful attempt to immortalize human-derived cells in vitro. The robust growth and unrestricted distribution of HeLa cells resulted in its broad adoption--both intentionally and through widespread cross-contamination--and for the past 60 years it has served a role analogous to that of a model organism. The cumulative impact of the HeLa cell line on research is demonstrated by its occurrence in more than 74,000 PubMed abstracts (approximately 0.3%). The genomic architecture of HeLa remains largely unexplored beyond its karyotype, partly because like many cancers, its extensive aneuploidy renders such analyses challenging. We carried out haplotype-resolved whole-genome sequencing of the HeLa CCL-2 strain, examined point- and indel-mutation variations, mapped copy-number variations and loss of heterozygosity regions, and phased variants across full chromosome arms. We also investigated variation and copy-number profiles for HeLa S3 and eight additional strains. We find that HeLa is relatively stable in terms of point variation, with few new mutations accumulating after early passaging. Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region of chromosome 8q24.21 at which integration of the human papilloma virus type 18 (HPV-18) genome occurred and that is likely to be the event that initiated tumorigenesis. We combined these maps with RNA-seq and ENCODE Project data sets to phase the HeLa epigenome. This revealed strong, haplotype-specific activation of the proto-oncogene MYC by the integrated HPV-18 genome approximately 500 kilobases upstream, and enabled global analyses of the relationship between gene dosage and expression. These data provide an extensively phased, high-quality reference genome for past and future experiments relying on HeLa, and demonstrate the value of haplotype resolution for characterizing cancer genomes and epigenomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740412/" 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/PMC3740412/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Adey, Andrew -- Burton, Joshua N -- Kitzman, Jacob O -- Hiatt, Joseph B -- Lewis, Alexandra P -- Martin, Beth K -- Qiu, Ruolan -- Lee, Choli -- Shendure, Jay -- AG039173/AG/NIA NIH HHS/ -- CA160080/CA/NCI NIH HHS/ -- F30 AG039173/AG/NIA NIH HHS/ -- HG006283/HG/NHGRI NIH HHS/ -- R01 HG006283/HG/NHGRI NIH HHS/ -- R21 CA160080/CA/NCI NIH HHS/ -- T32 GM007266/GM/NIGMS NIH HHS/ -- T32HG000035/HG/NHGRI NIH HHS/ -- England -- Nature. 2013 Aug 8;500(7461):207-11. doi: 10.1038/nature12064.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington, Seattle, Washington 98115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23925245" target="_blank"〉PubMed〈/a〉
    Keywords: Aneuploidy ; DNA Copy Number Variations ; *Epigenomics ; Female ; Genes, myc/genetics ; Genome, Human/*genetics ; Haplotypes ; HeLa Cells ; Human papillomavirus 18/genetics/physiology ; Humans ; Molecular Sequence Data ; Mutation ; Sequence Analysis, DNA ; Transcriptional Activation/genetics ; Uterine Cervical Neoplasms/genetics/pathology/virology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-12-20
    Description: We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031459/" 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/PMC4031459/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prufer, Kay -- Racimo, Fernando -- Patterson, Nick -- Jay, Flora -- Sankararaman, Sriram -- Sawyer, Susanna -- Heinze, Anja -- Renaud, Gabriel -- Sudmant, Peter H -- de Filippo, Cesare -- Li, Heng -- Mallick, Swapan -- Dannemann, Michael -- Fu, Qiaomei -- Kircher, Martin -- Kuhlwilm, Martin -- Lachmann, Michael -- Meyer, Matthias -- Ongyerth, Matthias -- Siebauer, Michael -- Theunert, Christoph -- Tandon, Arti -- Moorjani, Priya -- Pickrell, Joseph -- Mullikin, James C -- Vohr, Samuel H -- Green, Richard E -- Hellmann, Ines -- Johnson, Philip L F -- Blanche, Helene -- Cann, Howard -- Kitzman, Jacob O -- Shendure, Jay -- Eichler, Evan E -- Lein, Ed S -- Bakken, Trygve E -- Golovanova, Liubov V -- Doronichev, Vladimir B -- Shunkov, Michael V -- Derevianko, Anatoli P -- Viola, Bence -- Slatkin, Montgomery -- Reich, David -- Kelso, Janet -- Paabo, Svante -- 59107334/Howard Hughes Medical Institute/ -- GM100233/GM/NIGMS NIH HHS/ -- HG002385/HG/NHGRI NIH HHS/ -- HG006283/HG/NHGRI NIH HHS/ -- R01 GM040282/GM/NIGMS NIH HHS/ -- R01 GM100233/GM/NIGMS NIH HHS/ -- R01 HG002385/HG/NHGRI NIH HHS/ -- R01 HG006283/HG/NHGRI NIH HHS/ -- R01-GM40282/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jan 2;505(7481):43-9. doi: 10.1038/nature12886. Epub 2013 Dec 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. ; Department of Integrative Biology, University of California, Berkeley, California 94720-3140, USA. ; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany [2] Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China. ; 1] Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany [2] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Genome Technology Branch and NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Biomolecular Engineering, University of California, Santa Cruz, California 95064, USA. ; 1] Max F. Perutz Laboratories, Mathematics and Bioscience Group, Campus Vienna Biocenter 5, Vienna 1030, Austria [2] Ludwig-Maximilians-Universitat Munchen, Martinsried, 82152 Munich, Germany. ; Department of Biology, Emory University, Atlanta, Georgia 30322, USA. ; Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain (CEPH), 75010 Paris, France. ; 1] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA [2] Howard Hughes Medical Institute, Seattle, Washington 98195, USA. ; Allen Institute for Brain Science, Seattle, Washington 98103, USA. ; ANO Laboratory of Prehistory 14 Linia 3-11, St. Petersburg 1990 34, Russia. ; Palaeolithic Department, Institute of Archaeology and Ethnography, Russian Academy of Sciences, Siberian Branch, 630090 Novosibirsk, Russia. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24352235" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Animals ; Caves ; DNA Copy Number Variations/genetics ; Female ; *Fossils ; Gene Flow/genetics ; Gene Frequency ; Genome/*genetics ; Heterozygote ; Humans ; Inbreeding ; Models, Genetic ; Neanderthals/classification/*genetics ; Phylogeny ; Population Density ; Siberia/ethnology ; Toe Phalanges/anatomy & histology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2010-10-30
    Description: Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million "singly unique nucleotide" positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020103/" 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/PMC3020103/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sudmant, Peter H -- Kitzman, Jacob O -- Antonacci, Francesca -- Alkan, Can -- Malig, Maika -- Tsalenko, Anya -- Sampas, Nick -- Bruhn, Laurakay -- Shendure, Jay -- 1000 Genomes Project -- Eichler, Evan E -- 085532/Wellcome Trust/United Kingdom -- HG004120/HG/NHGRI NIH HHS/ -- P01 HG004120/HG/NHGRI NIH HHS/ -- P01 HG004120-03/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Oct 29;330(6004):641-6. doi: 10.1126/science.1197005.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21030649" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosome Mapping ; Continental Population Groups/genetics ; *DNA Copy Number Variations ; Databases, Nucleic Acid ; Evolution, Molecular ; Female ; Gene Conversion ; *Gene Dosage ; *Gene Duplication ; Gene Frequency ; Genes, Duplicate ; *Genetic Variation ; *Genome, Human ; Genomics/*methods ; Genotype ; Haplotypes ; Humans ; Male ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA
    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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  • 4
    Publication Date: 2015-12-19
    Description: Speciation, the process by which new biological species arise, involves the evolution of reproductive barriers, such as hybrid sterility or inviability between populations. However, identifying hybrid incompatibility genes remains a key obstacle in understanding the molecular basis of reproductive isolation. We devised a genomic screen, which identified a cell cycle-regulation gene as the cause of male inviability in hybrids resulting from a cross between Drosophila melanogaster and D. simulans. Ablation of the D. simulans allele of this gene is sufficient to rescue the adult viability of hybrid males. This dominantly acting cell cycle regulator causes mitotic arrest and, thereby, inviability of male hybrid larvae. Our genomic method provides a facile means to accelerate the identification of hybrid incompatibility genes in other model and nonmodel systems.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703311/" 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/PMC4703311/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Phadnis, Nitin -- Baker, EmilyClare P -- Cooper, Jacob C -- Frizzell, Kimberly A -- Hsieh, Emily -- de la Cruz, Aida Flor A -- Shendure, Jay -- Kitzman, Jacob O -- Malik, Harmit S -- 5T32 HD0741/HD/NICHD NIH HHS/ -- HG006283/HG/NHGRI NIH HHS/ -- R01 GM074108/GM/NIGMS NIH HHS/ -- R01 GM115914/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1552-5. doi: 10.1126/science.aac7504.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. nitin.phadnis@utah.edu hsmalik@fhcrc.org. ; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. ; Genome Sciences, University of Washington, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. ; Genome Sciences, University of Washington, Seattle, WA 98195, USA. Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA. ; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. nitin.phadnis@utah.edu hsmalik@fhcrc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680200" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Carrier Proteins/genetics/*physiology ; Cell Cycle/*genetics ; Chimera/genetics ; Crosses, Genetic ; Drosophila melanogaster/*genetics/growth & development ; Drosophila simulans/*genetics/growth & development ; Gene Expression Regulation, Developmental ; Genes, Essential/genetics/physiology ; Genes, Insect ; Genes, Lethal/genetics/*physiology ; *Genetic Speciation ; Male ; Molecular Sequence Data ; *Reproductive Isolation
    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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