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PMID: 22936568 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

A high-coverage genome sequence from an archaic Denisovan individual.

Science (New York, N.Y.) ·Vol. 338 ·No. 6104 ·2012-10-12 ·Pages 222-6

Meyer M, Kircher M, Gansauge MT, Li H, Racimo F, Mallick S, Schraiber JG, Jay F, Prüfer K, de Filippo C, Sudmant PH, Alkan C, Fu Q, Do R, Rohland N, Tandon A, Siebauer M, Green RE, Bryc K, Briggs AW, Stenzel U, Dabney J, Shendure J, Kitzman J, Hammer MF, Shunkov MV, Derevianko AP, Patterson N, Andrés AM, Eichler EE, Slatkin M, Reich D, Kelso J, Pääbo S

Abstract

We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30×) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of "missing evolution" in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.

MeSH Terms
Alleles Animals Base Sequence Fossils Gene Flow Gene Library Genetic Variation Genome, Human/genetics Heterozygote Humans Molecular Sequence Data Neanderthals/genetics Sequence Analysis, DNA
Authors & Affiliations
34 authors, click to expand affiliations / ORCID
Meyer Matthias
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany. mmeyer@eva.mpg.de
Kircher Martin
Gansauge Marie-Theres
Li Heng
Racimo Fernando
Mallick Swapan
Schraiber Joshua G
Jay Flora
Prüfer Kay
de Filippo Cesare
Sudmant Peter H
Alkan Can
Fu Qiaomei
Do Ron
Rohland Nadin
Tandon Arti
Siebauer Michael
Green Richard E
Bryc Katarzyna
Briggs Adrian W
Stenzel Udo
Dabney Jesse
Shendure Jay
Kitzman Jacob
Hammer Michael F
Shunkov Michael V
Derevianko Anatoli P
Patterson Nick
Andrés Aida M
Eichler Evan E
Slatkin Montgomery
Reich David
Kelso Janet
Pääbo Svante
References (190)
190 references, click to expand
  1. Cost-effective, high-throughput DNA sequencing libraries for multiplexed target capture.
    Genome Res. 2012 May;22(5):939-46 PMID: 22267522
  2. An activating mutation in the murine erythropoietin receptor induces erythroleukemia in mice: a cytokine receptor superfamily oncogene.
    Cell. 1991 Dec 20;67(6):1089-102 PMID: 1662116
  3. The ratio of human X chromosome to autosome diversity is positively correlated with genetic distance from genes.
    Nat Genet. 2010 Oct;42(10):830-1 PMID: 20802480
  4. Testing for ancient admixture between closely related populations.
    Mol Biol Evol. 2011 Aug;28(8):2239-52 PMID: 21325092
  5. The flavin-containing monooxygenase 2 gene (FMO2) of humans, but not of other primates, encodes a truncated, nonfunctional protein.
    J Biol Chem. 1998 Nov 13;273(46):30599-607 PMID: 9804831
  6. Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form.
    Hum Mutat. 2008 Dec;29(12):1405-11 PMID: 18561327
  7. Out of Africa: modern human origins special feature: the origin of Neandertals.
    Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16022-7 PMID: 19805257
  8. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.
    Nature. 2005 Feb 17;433(7027):769-73 PMID: 15685193
  9. Fast and accurate short read alignment with Burrows-Wheeler transform.
    Bioinformatics. 2009 Jul 15;25(14):1754-60 PMID: 19451168
  10. Genetic signatures of strong recent positive selection at the lactase gene.
    Am J Hum Genet. 2004 Jun;74(6):1111-20 PMID: 15114531
  11. Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA.
    Nucleic Acids Res. 2010 Apr;38(6):e87 PMID: 20028723
  12. Taurodontism: a review of the condition and endodontic treatment challenges.
    Int Endod J. 2008 May;41(5):375-88 PMID: 18363703
  13. mlRho - a program for estimating the population mutation and recombination rates from shotgun-sequenced diploid genomes.
    Mol Ecol. 2010 Mar;19 Suppl 1:277-84 PMID: 20331786
  14. A functional genetic link between distinct developmental language disorders.
    N Engl J Med. 2008 Nov 27;359(22):2337-45 PMID: 18987363
  15. X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis.
    Am J Hum Genet. 1992 Nov;51(5):1136-49 PMID: 1415255
  16. Huntingtin interacts with a family of WW domain proteins.
    Hum Mol Genet. 1998 Sep;7(9):1463-74 PMID: 9700202
  17. Membrane organization of the dystrophin-glycoprotein complex.
    Cell. 1991 Sep 20;66(6):1121-31 PMID: 1913804
  18. Translation initiation on mammalian mRNAs with structured 5'UTRs requires DExH-box protein DHX29.
    Cell. 2008 Dec 26;135(7):1237-50 PMID: 19109895
  19. Origins and functional impact of copy number variation in the human genome.
    Nature. 2010 Apr 1;464(7289):704-12 PMID: 19812545
  20. Origin of human chromosome 2: an ancestral telomere-telomere fusion.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9051-5 PMID: 1924367
  21. Variation in genome-wide mutation rates within and between human families.
    Nat Genet. 2011 Jun 12;43(7):712-4 PMID: 21666693
  22. Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans.
    Nat Genet. 2007 Oct;39(10):1251-5 PMID: 17828266
  23. Genetic evidence for a higher female migration rate in humans.
    Nat Genet. 1998 Nov;20(3):278-80 PMID: 9806547
  24. Improved base calling for the Illumina Genome Analyzer using machine learning strategies.
    Genome Biol. 2009;10(8):R83 PMID: 19682367
  25. An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids.
    Lancet. 1984 Nov 10;2(8411):1058-61 PMID: 6150139
  26. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
    Genome Biol. 2009;10(3):R25 PMID: 19261174
  27. Human erythropoietin receptor: cloning, expression, and biologic characterization.
    Blood. 1990 Jul 1;76(1):31-5 PMID: 2163696
  28. A map of human genome variation from population-scale sequencing.
    Nature. 2010 Oct 28;467(7319):1061-73 PMID: 20981092
  29. Genetic evidence for complex speciation of humans and chimpanzees.
    Nature. 2006 Jun 29;441(7097):1103-8 PMID: 16710306
  30. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.
    Science. 2007 May 11;316(5826):889-94 PMID: 17434869
  31. Genomewide association studies and assessment of the risk of disease.
    N Engl J Med. 2010 Jul 8;363(2):166-76 PMID: 20647212
  32. Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro.
    J Neurosci. 2008 Mar 12;28(11):2933-40 PMID: 18337424
  33. Isolation and characterization of a thermostable RNA ligase 1 from a Thermus scotoductus bacteriophage TS2126 with good single-stranded DNA ligation properties.
    Nucleic Acids Res. 2005 Jan 07;33(1):135-42 PMID: 15642699
  34. The evolutionary significance of cis-regulatory mutations.
    Nat Rev Genet. 2007 Mar;8(3):206-16 PMID: 17304246
  35. True single-molecule DNA sequencing of a pleistocene horse bone.
    Genome Res. 2011 Oct;21(10):1705-19 PMID: 21803858
  36. OPRM1 and EGFR contribute to skin pigmentation differences between Indigenous Americans and Europeans.
    Hum Genet. 2012 Jul;131(7):1073-80 PMID: 22198722
  37. Bupropion efficacy for smoking cessation is influenced by the DRD2 Taq1A polymorphism: analysis of pooled data from two clinical trials.
    Nicotine Tob Res. 2007 Dec;9(12):1251-7 PMID: 18058343
  38. The UCSC Genome Browser database: update 2011.
    Nucleic Acids Res. 2011 Jan;39(Database issue):D876-82 PMID: 20959295
  39. A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation.
    Am J Hum Genet. 2007 Feb;80(2):241-52 PMID: 17236130
  40. Contrasting properties of gene-specific regulatory, coding, and copy number mutations in Saccharomyces cerevisiae: frequency, effects, and dominance.
    PLoS Genet. 2012 Feb;8(2):e1002497 PMID: 22346762
  41. Evolution of the large secreted gel-forming mucins.
    Mol Biol Evol. 2000 Aug;17(8):1175-84 PMID: 10908637
  42. The origin of man: a chromosomal pictorial legacy.
    Science. 1982 Mar 19;215(4539):1525-30 PMID: 7063861
  43. SNPedia: a wiki supporting personal genome annotation, interpretation and analysis.
    Nucleic Acids Res. 2012 Jan;40(Database issue):D1308-12 PMID: 22140107
  44. Insights into hominid evolution from the gorilla genome sequence.
    Nature. 2012 Mar 07;483(7388):169-75 PMID: 22398555
  45. A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism.
    Am J Hum Genet. 2008 Jan;82(1):160-4 PMID: 18179894
  46. Characterization of Escherichia coli endonuclease VIII.
    J Biol Chem. 1997 Dec 19;272(51):32230-9 PMID: 9405426
  47. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data.
    Genome Res. 2010 Sep;20(9):1297-303 PMID: 20644199
  48. Gorilla genome structural variation reveals evolutionary parallelisms with chimpanzee.
    Genome Res. 2011 Oct;21(10):1640-9 PMID: 21685127
  49. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.
    Genome Res. 2005 Aug;15(8):1034-50 PMID: 16024819
  50. Strong reproductive isolation between humans and Neanderthals inferred from observed patterns of introgression.
    Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15129-34 PMID: 21911389
  51. Evolutionary changes of the number of olfactory receptor genes in the human and mouse lineages.
    Gene. 2005 Feb 14;346:23-8 PMID: 15716099
  52. Recent segmental duplications in the human genome.
    Science. 2002 Aug 9;297(5583):1003-7 PMID: 12169732
  53. Insulators and promoters: closer than we think.
    Nat Rev Genet. 2010 Jun;11(6):439-46 PMID: 20442713
  54. Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans.
    Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21437-41 PMID: 19934046
  55. ENCODE whole-genome data in the UCSC Genome Browser: update 2012.
    Nucleic Acids Res. 2012 Jan;40(Database issue):D912-7 PMID: 22075998
  56. Genome-wide nucleotide-level mammalian ancestor reconstruction.
    Genome Res. 2008 Nov;18(11):1829-43 PMID: 18849525
  57. The T allele of a single-nucleotide polymorphism 13.9 kb upstream of the lactase gene (LCT) (C-13.9kbT) does not predict or cause the lactase-persistence phenotype in Africans.
    Am J Hum Genet. 2004 Jun;74(6):1102-10 PMID: 15106124
  58. A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing.
    Cell. 2008 Aug 8;134(3):416-26 PMID: 18692465
  59. Independent histories of human Y chromosomes from Melanesia and Australia.
    Am J Hum Genet. 2001 Jan;68(1):173-190 PMID: 11115381
  60. The human inward rectifier K(+) channel subunit kir5.1 (KCNJ16) maps to chromosome 17q25 and is expressed in kidney and pancreas.
    Cytogenet Cell Genet. 2000;90(1-2):60-3 PMID: 11060447
  61. Illumina sequencing library preparation for highly multiplexed target capture and sequencing.
    Cold Spring Harb Protoc. 2010 Jun;2010(6):pdb.prot5448 PMID: 20516186
  62. A SNP in the ABCC11 gene is the determinant of human earwax type.
    Nat Genet. 2006 Mar;38(3):324-30 PMID: 16444273
  63. Length and GC-biases during sequencing library amplification: a comparison of various polymerase-buffer systems with ancient and modern DNA sequencing libraries.
    Biotechniques. 2012 Feb;52(2):87-94 PMID: 22313406
  64. A human genome diversity cell line panel.
    Science. 2002 Apr 12;296(5566):261-2 PMID: 11954565
  65. Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells.
    Genome Res. 2008 Apr;18(4):610-21 PMID: 18285502
  66. MicroRNA-driven developmental remodeling in the brain distinguishes humans from other primates.
    PLoS Biol. 2011 Dec;9(12):e1001214 PMID: 22162950
  67. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA.
    Nature. 2000 Nov 2;408(6808):86-9 PMID: 11081512
  68. Herc5 attenuates influenza A virus by catalyzing ISGylation of viral NS1 protein.
    J Immunol. 2010 May 15;184(10):5777-90 PMID: 20385878
  69. Specificities and kinetics of uracil excision from uracil-containing DNA oligomers by Escherichia coli uracil DNA glycosylase.
    Biochemistry. 1991 Apr 23;30(16):4055-61 PMID: 2018771
  70. Archaic human ancestry in East Asia.
    Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18301-6 PMID: 22042846
  71. Initial sequence of the chimpanzee genome and comparison with the human genome.
    Nature. 2005 Sep 1;437(7055):69-87 PMID: 16136131
  72. A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color.
    Am J Hum Genet. 2008 Feb;82(2):424-31 PMID: 18252222
  73. Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2.
    N Engl J Med. 2006 Mar 30;354(13):1370-7 PMID: 16571880
  74. Temporal patterns of nucleotide misincorporations and DNA fragmentation in ancient DNA.
    PLoS One. 2012;7(3):e34131 PMID: 22479540
  75. Double indexing overcomes inaccuracies in multiplex sequencing on the Illumina platform.
    Nucleic Acids Res. 2012 Jan;40(1):e3 PMID: 22021376
  76. Expression patterns of PRDM10 during mouse embryonic development.
    BMB Rep. 2010 Jan;43(1):29-33 PMID: 20132732
  77. Attention-deficit/hyperactivity disorder phenotype is influenced by a functional catechol-O-methyltransferase variant.
    J Neural Transm (Vienna). 2010 Feb;117(2):259-67 PMID: 19946713
  78. Classic selective sweeps were rare in recent human evolution.
    Science. 2011 Feb 18;331(6019):920-4 PMID: 21330547
  79. Evolutionary and biomedical insights from the rhesus macaque genome.
    Science. 2007 Apr 13;316(5822):222-34 PMID: 17431167
  80. Structure-independent and quantitative ligation of single-stranded DNA.
    Anal Biochem. 2006 Feb 15;349(2):242-6 PMID: 16325753
  81. A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice.
    Cell. 2009 May 29;137(5):961-71 PMID: 19490899
  82. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data.
    Nucleic Acids Res. 2010 Sep;38(16):e164 PMID: 20601685
  83. Genomic signatures of germline gene expression.
    Genome Res. 2010 Nov;20(11):1503-11 PMID: 20686123
  84. The UCSC Genome Browser Database: 2008 update.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D773-9 PMID: 18086701
  85. The genetic association database.
    Nat Genet. 2004 May;36(5):431-2 PMID: 15118671
  86. The human erythropoietin receptor gene rescues erythropoiesis and developmental defects in the erythropoietin receptor null mouse.
    Blood. 2001 Jul 15;98(2):475-7 PMID: 11435319
  87. Apolipoprotein E genetic variation and Alzheimer's disease. a meta-analysis.
    Dement Geriatr Cogn Disord. 1999 May-Jun;10(3):199-209 PMID: 10325447
  88. The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression.
    Curr Biol. 2007 Mar 20;17(6):488-98 PMID: 17346968
  89. The effects of catechol O-methyltransferase genotype on brain activation elicited by affective stimuli and cognitive tasks.
    Rev Neurosci. 2006;17(3):359-67 PMID: 16878403
  90. Genetic susceptibility to schizophrenia: role of dopaminergic pathway gene polymorphisms.
    Pharmacogenomics. 2009 Feb;10(2):277-91 PMID: 19207030
  91. The Human Gene Mutation Database: providing a comprehensive central mutation database for molecular diagnostics and personalized genomics.
    Hum Genomics. 2009 Dec;4(2):69-72 PMID: 20038494
  92. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes.
    J Clin Invest. 2007 Aug;117(8):2155-63 PMID: 17671651
  93. Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms.
    Nature. 2004 May 6;429(6987):75-9 PMID: 15129283
  94. RICS, a novel GTPase-activating protein for Cdc42 and Rac1, is involved in the beta-catenin-N-cadherin and N-methyl-D-aspartate receptor signaling.
    J Biol Chem. 2003 Mar 14;278(11):9920-7 PMID: 12531901
  95. JASPAR, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D102-6 PMID: 18006571
  96. Widespread genomic signatures of natural selection in hominid evolution.
    PLoS Genet. 2009 May;5(5):e1000471 PMID: 19424416
  97. Comparative and demographic analysis of orang-utan genomes.
    Nature. 2011 Jan 27;469(7331):529-33 PMID: 21270892
  98. A framework for variation discovery and genotyping using next-generation DNA sequencing data.
    Nat Genet. 2011 May;43(5):491-8 PMID: 21478889
  99. A new gene, EVC2, is mutated in Ellis-van Creveld syndrome.
    Mol Genet Metab. 2002 Dec;77(4):291-5 PMID: 12468274
  100. The status of Homo heidelbergensis (Schoetensack 1908).
    Evol Anthropol. 2012 May;21(3):101-7 PMID: 22718477
  101. Convergent adaptation of human lactase persistence in Africa and Europe.
    Nat Genet. 2007 Jan;39(1):31-40 PMID: 17159977
  102. Human pigmentation phenotype: a point mutation generates nonfunctional MSH receptor.
    Biochem Biophys Res Commun. 1998 Apr 17;245(2):490-2 PMID: 9571181
  103. Enredo and Pecan: genome-wide mammalian consistency-based multiple alignment with paralogs.
    Genome Res. 2008 Nov;18(11):1814-28 PMID: 18849524
  104. Segmental duplication associated with the human-specific inversion of chromosome 18: a further example of the impact of segmental duplications on karyotype and genome evolution in primates.
    Hum Genet. 2004 Jul;115(2):116-22 PMID: 15133654
  105. Genetic history of an archaic hominin group from Denisova Cave in Siberia.
    Nature. 2010 Dec 23;468(7327):1053-60 PMID: 21179161
  106. Cloning, primary sequence and chromosomal localization of human FMO2, a new member of the flavin-containing mono-oxygenase family.
    Biochem J. 1992 Oct 1;287 ( Pt 1):261-7 PMID: 1417778
  107. Inversion, duplication, and changes in gene context are associated with human chromosome 18 evolution.
    Genomics. 2004 Mar;83(3):493-501 PMID: 14962675
  108. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data.
    Bioinformatics. 2011 Nov 1;27(21):2987-93 PMID: 21903627
  109. Population size changes reshape genomic patterns of diversity.
    Evolution. 2007 Dec;61(12):3001-6 PMID: 17971168
  110. A population-specific HTR2B stop codon predisposes to severe impulsivity.
    Nature. 2010 Dec 23;468(7327):1061-6 PMID: 21179162
  111. Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6.
    Nat Genet. 2003 Feb;33(2):145-53 PMID: 12548288
  112. Influence of DRD2 and ANKK1 genotypes on apomorphine-induced growth hormone (GH) response in alcohol-dependent patients.
    Prog Neuropsychopharmacol Biol Psychiatry. 2010 Feb 1;34(1):45-9 PMID: 19796663
  113. Variation in the mutation rate across mammalian genomes.
    Nat Rev Genet. 2011 Oct 04;12(11):756-66 PMID: 21969038
  114. Widespread changes in protein synthesis induced by microRNAs.
    Nature. 2008 Sep 4;455(7209):58-63 PMID: 18668040
  115. Studies of three Amerindian populations using nuclear DNA polymorphisms.
    Hum Biol. 1991 Dec;63(6):775-94 PMID: 1683642
  116. The ISG15 conjugation system broadly targets newly synthesized proteins: implications for the antiviral function of ISG15.
    Mol Cell. 2010 Jun 11;38(5):722-32 PMID: 20542004
  117. Human mu opiate receptor. cDNA and genomic clones, pharmacologic characterization and chromosomal assignment.
    FEBS Lett. 1994 Jan 31;338(2):217-22 PMID: 7905839
  118. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex.
    Cell. 2008 May 16;133(4):653-65 PMID: 18485873
  119. Genome sequencing in microfabricated high-density picolitre reactors.
    Nature. 2005 Sep 15;437(7057):376-80 PMID: 16056220
  120. Inference of population splits and mixtures from genome-wide allele frequency data.
    PLoS Genet. 2012;8(11):e1002967 PMID: 23166502
  121. Ancient DNA extraction from bones and teeth.
    Nat Protoc. 2007;2(7):1756-62 PMID: 17641642
  122. Spread of an inactive form of caspase-12 in humans is due to recent positive selection.
    Am J Hum Genet. 2006 Apr;78(4):659-70 PMID: 16532395
  123. Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression.
    Hum Genet. 2008 Mar;123(2):177-87 PMID: 18172690
  124. A complete mtDNA genome of an early modern human from Kostenki, Russia.
    Curr Biol. 2010 Feb 9;20(3):231-6 PMID: 20045327
  125. Accurate whole human genome sequencing using reversible terminator chemistry.
    Nature. 2008 Nov 6;456(7218):53-9 PMID: 18987734
  126. Targeted investigation of the Neandertal genome by array-based sequence capture.
    Science. 2010 May 7;328(5979):723-5 PMID: 20448179
  127. Transmitted duplication of 8p23.1-8p23.2 associated with speech delay, autism and learning difficulties.
    Eur J Hum Genet. 2009 Jan;17(1):37-43 PMID: 18716609
  128. Physical mapping by FISH of the DiGeorge critical region (DGCR): involvement of the region in familial cases.
    Am J Hum Genet. 1993 Dec;53(6):1239-49 PMID: 8250039
  129. Polymorphism of the androgen receptor gene is associated with male pattern baldness.
    J Invest Dermatol. 2001 Mar;116(3):452-5 PMID: 11231320
  130. Calibrating a coalescent simulation of human genome sequence variation.
    Genome Res. 2005 Nov;15(11):1576-83 PMID: 16251467
  131. The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers.
    Mol Psychiatry. 1998 May;3(3):256-60 PMID: 9672901
  132. The onconeural antigen Nova-1 is a neuron-specific RNA-binding protein, the activity of which is inhibited by paraneoplastic antibodies.
    J Neurosci. 1996 Feb 1;16(3):1114-22 PMID: 8558240
  133. The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes.
    Eur J Hum Genet. 2008 Mar;16(3):391-4 PMID: 18043716
  134. Natural selection has driven population differentiation in modern humans.
    Nat Genet. 2008 Mar;40(3):340-5 PMID: 18246066
  135. Analyses of X-linked and autosomal genetic variation in population-scale whole genome sequencing.
    Nat Genet. 2011 Jul 24;43(8):741-3 PMID: 21775991
  136. Predicting deleterious amino acid substitutions.
    Genome Res. 2001 May;11(5):863-74 PMID: 11337480
  137. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
    Nature. 2007 Jun 7;447(7145):661-78 PMID: 17554300
  138. [The meaning of taurodontism in oral surgery--case report].
    Acta Stomatol Croat. 1991;25(2):123-7 PMID: 1819934
  139. FUNC: a package for detecting significant associations between gene sets and ontological annotations.
    BMC Bioinformatics. 2007 Feb 06;8:41 PMID: 17284313
  140. Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor.
    Bioinformatics. 2010 Aug 15;26(16):2069-70 PMID: 20562413
  141. Paleoanthropology. Who were the Denisovans?
    Science. 2011 Aug 26;333(6046):1084-7 PMID: 21868646
  142. Prefrontal and striatal dopaminergic genes predict individual differences in exploration and exploitation.
    Nat Neurosci. 2009 Aug;12(8):1062-8 PMID: 19620978
  143. Doubts about complex speciation between humans and chimpanzees.
    Trends Ecol Evol. 2009 Oct;24(10):533-40 PMID: 19664844
  144. Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome.
    Am J Hum Genet. 2003 Mar;72(3):728-32 PMID: 12571802
  145. The bonobo genome compared with the chimpanzee and human genomes.
    Nature. 2012 Jun 28;486(7404):527-31 PMID: 22722832
  146. The genomic record of Humankind's evolutionary roots.
    Am J Hum Genet. 1999 Jan;64(1):31-9 PMID: 9915940
  147. Denaturing HPLC profiling of the ABCA4 gene for reliable detection of allelic variations.
    Clin Chem. 2004 Aug;50(8):1336-43 PMID: 15192030
  148. A draft sequence of the Neandertal genome.
    Science. 2010 May 7;328(5979):710-722 PMID: 20448178
  149. A method and server for predicting damaging missense mutations.
    Nat Methods. 2010 Apr;7(4):248-9 PMID: 20354512
  150. The complete mitochondrial DNA genome of an unknown hominin from southern Siberia.
    Nature. 2010 Apr 8;464(7290):894-7 PMID: 20336068
  151. CTCFBSDB: a CTCF-binding site database for characterization of vertebrate genomic insulators.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D83-7 PMID: 17981843
  152. Properties of human red cell spectrin heterodimer (side-to-side) assembly and identification of an essential nucleation site.
    J Biol Chem. 1992 Jul 25;267(21):14775-82 PMID: 1634521
  153. Genomewide association studies and human disease.
    N Engl J Med. 2009 Apr 23;360(17):1759-68 PMID: 19369657
  154. A common variation in EDAR is a genetic determinant of shovel-shaped incisors.
    Am J Hum Genet. 2009 Oct;85(4):528-35 PMID: 19804850
  155. Predicting Homo pigmentation phenotype through genomic data: from Neanderthal to James Watson.
    Am J Hum Biol. 2012 Sep-Oct;24(5):705-9 PMID: 22411106
  156. Cloning and characterization of a novel human clathrin heavy chain gene (CLTCL).
    Genomics. 1996 Aug 1;35(3):466-72 PMID: 8844170
  157. Taurodontism: the incidence and possible significance of the trait.
    Aust Dent J. 1976 Jun;21(3):272-6 PMID: 791224
  158. Strong male-driven evolution of DNA sequences in humans and apes.
    Nature. 2002 Apr 11;416(6881):624-6 PMID: 11948348
  159. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
    Cell. 1993 Mar 26;72(6):971-83 PMID: 8458085
  160. Sequence variants in SLITRK1 are associated with Tourette's syndrome.
    Science. 2005 Oct 14;310(5746):317-20 PMID: 16224024
  161. Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9.
    J Biol Chem. 2002 Apr 19;277(16):14246-54 PMID: 11834742
  162. Detecting autozygosity through runs of homozygosity: a comparison of three autozygosity detection algorithms.
    BMC Genomics. 2011 Sep 23;12:460 PMID: 21943305
  163. Genomic runs of homozygosity record population history and consanguinity.
    PLoS One. 2010 Nov 15;5(11):e13996 PMID: 21085596
  164. Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy.
    Cell. 1994 Aug 26;78(4):625-33 PMID: 8069911
  165. Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.
    Am J Hum Genet. 2008 Jan;82(1):150-9 PMID: 18179893
  166. Izumo is part of a multiprotein family whose members form large complexes on mammalian sperm.
    Mol Reprod Dev. 2009 Dec;76(12):1188-99 PMID: 19658160
  167. Two novel heterozygous mutations of EVC2 cause a mild phenotype of Ellis-van Creveld syndrome in a Chinese family.
    Am J Med Genet A. 2011 Sep;155A(9):2131-6 PMID: 21815252
  168. Identification of a variant associated with adult-type hypolactasia.
    Nat Genet. 2002 Feb;30(2):233-7 PMID: 11788828
  169. Diversity of human copy number variation and multicopy genes.
    Science. 2010 Oct 29;330(6004):641-6 PMID: 21030649
  170. From micrograms to picograms: quantitative PCR reduces the material demands of high-throughput sequencing.
    Nucleic Acids Res. 2008 Jan;36(1):e5 PMID: 18084031
  171. Targeted retrieval and analysis of five Neandertal mtDNA genomes.
    Science. 2009 Jul 17;325(5938):318-21 PMID: 19608918
  172. The Sequence Alignment/Map format and SAMtools.
    Bioinformatics. 2009 Aug 15;25(16):2078-9 PMID: 19505943
  173. The impact of recombination on nucleotide substitutions in the human genome.
    PLoS Genet. 2008 May 09;4(5):e1000071 PMID: 18464896
  174. Personalized copy number and segmental duplication maps using next-generation sequencing.
    Nat Genet. 2009 Oct;41(10):1061-7 PMID: 19718026
  175. Denisova admixture and the first modern human dispersals into Southeast Asia and Oceania.
    Am J Hum Genet. 2011 Oct 7;89(4):516-28 PMID: 21944045
  176. Detecting ancient admixture and estimating demographic parameters in multiple human populations.
    Mol Biol Evol. 2009 Aug;26(8):1823-7 PMID: 19420049
  177. Patterns of damage in genomic DNA sequences from a Neandertal.
    Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14616-21 PMID: 17715061
  178. ABRUPT CLINE FOR SEX CHROMOSOMES IN A HYBRID ZONE BETWEEN TWO SPECIES OF MICE.
    Evolution. 1992 Aug;46(4):1146-1163 PMID: 28564395
  179. Inference of human population history from individual whole-genome sequences.
    Nature. 2011 Jul 13;475(7357):493-6 PMID: 21753753
  180. Analysis of high-throughput ancient DNA sequencing data.
    Methods Mol Biol. 2012;840:197-228 PMID: 22237537
  181. A mutation in adenylosuccinate lyase associated with mental retardation and autistic features.
    Nat Genet. 1992 Apr;1(1):59-63 PMID: 1302001
  182. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.
    PLoS Genet. 2011 Oct;7(10):e1002326 PMID: 22022285
  183. Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle.
    Nature. 1992 Dec 10;360(6404):588-91 PMID: 1461282
  184. The history of African gene flow into Southern Europeans, Levantines, and Jews.
    PLoS Genet. 2011 Apr;7(4):e1001373 PMID: 21533020
  185. Sex-biased migration in humans: what should we expect from genetic data?
    Bioessays. 2006 Mar;28(3):290-300 PMID: 16479583
  186. A forkhead-domain gene is mutated in a severe speech and language disorder.
    Nature. 2001 Oct 4;413(6855):519-23 PMID: 11586359
  187. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm.
    Nat Protoc. 2009;4(7):1073-81 PMID: 19561590
  188. LUZP deficiency affects neural tube closure during brain development.
    Biochem Biophys Res Commun. 2008 Nov 21;376(3):466-71 PMID: 18801334
  189. Instability and decay of the primary structure of DNA.
    Nature. 1993 Apr 22;362(6422):709-15 PMID: 8469282
  190. Gene flow and species delimitation.
    Trends Ecol Evol. 2009 Jul;24(7):386-93 PMID: 19409650
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1224344
Email
mmeyer@eva.mpg.de
Published
2012-10-12
Epub
2012-00-30
Pages
222-6
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3617501
Subset
IM
Grants
NIGMS NIH HHS · R01-GM40282 · United States
NIGMS NIH HHS · R01 GM100233 · United States
NIGMS NIH HHS · R01 GM040282 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · GM100233 · United States
External Links
PubMed source DOI: 10.1126/science.1224344 PMC Full Text View journal details
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