Dog10K: an international sequencing effort to advance studies of canine domestication, phenotypes and health

ABSTRACT Dogs are the most phenotypically diverse mammalian species, and they possess more known heritable disorders than any other non-human mammal. Efforts to catalog and characterize genetic variation across well-chosen populations of canines are necessary to advance our understanding of their evolutionary history and genetic architecture. To date, no organized effort has been undertaken to sequence the world's canid populations. The Dog10K Consortium (http://www.dog10kgenomes.org) is an international collaboration of researchers from across the globe who will generate 20× whole genomes from 10 000 canids in 5 years. This effort will capture the genetic diversity that underlies the phenotypic and geographical variability of modern canids worldwide. Breeds, village dogs, niche populations and extended pedigrees are currently being sequenced, and de novo assemblies of multiple canids are being constructed. This unprecedented dataset will address the genetic underpinnings of domestication, breed formation, aging, behavior and morphological variation. More generally, this effort will advance our understanding of human and canine health.

[1]  R. Wayne,et al.  The genealogy and genetic viability of reintroduced Yellowstone grey wolves , 2008, Molecular ecology.

[2]  Matthew Breen,et al.  Comparative oncology: what dogs and other species can teach us about humans with cancer , 2015, Philosophical Transactions of the Royal Society B: Biological Sciences.

[3]  M. Świtoński,et al.  Sequence analysis of three canine adipokine genes revealed an association between TNF polymorphisms and obesity in Labrador dogs. , 2016, Animal genetics.

[4]  Holly C. Beale,et al.  Variation of BMP3 Contributes to Dog Breed Skull Diversity , 2012, PLoS genetics.

[5]  N. Cottam,et al.  Blanket and flank sucking in Doberman Pinschers. , 2007, Journal of the American Veterinary Medical Association.

[6]  C. T. Brown,et al.  Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2 which contributes to Robinow-like syndrome in Bulldogs and related screw tail dog breeds , 2018, PLoS genetics.

[7]  K. Lindblad-Toh,et al.  A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs , 2016, Cell metabolism.

[8]  Keith Dobney,et al.  Genomic and archaeological evidence suggest a dual origin of domestic dogs , 2016, Science.

[9]  Chung-I Wu,et al.  The genomics of selection in dogs and the parallel evolution between dogs and humans , 2013, Nature Communications.

[10]  C. Bustamante,et al.  Molecular and Evolutionary History of Melanism in North American Gray Wolves , 2009, Science.

[11]  Ayellet V. Segrè,et al.  Hundreds of variants clustered in genomic loci and biological pathways affect human height , 2010, Nature.

[12]  E. Teske,et al.  Morphological Distinction of Histiocytic Sarcoma from Other Tumor Types in Bernese Mountain Dogs and Flatcoated Retrievers. , 2018, In vivo.

[13]  K. Lindblad-Toh,et al.  The genomic signature of dog domestication reveals adaptation to a starch-rich diet , 2013, Nature.

[14]  E. Ostrander,et al.  Single-Nucleotide-Polymorphism-Based Association Mapping of Dog Stereotypes , 2008, Genetics.

[15]  E. Kirkness,et al.  Breed relationships facilitate fine-mapping studies: a 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds. , 2007, Genome research.

[16]  R. Bronson,et al.  Tail chasing in a bull terrier. , 1993, Journal of the American Veterinary Medical Association.

[17]  K. Svenson,et al.  Canine Brachycephaly Is Associated with a Retrotransposon-Mediated Missplicing of SMOC2 , 2017, Current Biology.

[18]  C. O'Callaghan,et al.  The Canine POMC Gene, Obesity in Labrador Retrievers and Susceptibility to Diabetes Mellitus , 2017, Journal of veterinary internal medicine.

[19]  C. Khanna,et al.  Catching Cancer by the Tail: New Perspectives on the Use of Kinase Inhibitors , 2009, Clinical Cancer Research.

[20]  E. Ostrander,et al.  Analysis of large versus small dogs reveals three genes on the canine X chromosome associated with body weight, muscling and back fat thickness , 2017, PLoS genetics.

[21]  Kerstin Lindblad-Toh,et al.  Leader of the pack: gene mapping in dogs and other model organisms , 2008, Nature Reviews Genetics.

[22]  H Lohi,et al.  The canine era: the rise of a biomedical model. , 2016, Animal genetics.

[23]  Qing Zhou,et al.  iDog: an integrated resource for domestic dogs and wild canids , 2018, Nucleic Acids Res..

[24]  E. Ostrander,et al.  Morphometrics within dog breeds are highly reproducible and dispute Rensch’s rule , 2008, Mammalian Genome.

[25]  E. Ostrander,et al.  The insulin-like growth factor 1 receptor (IGF1R) contributes to reduced size in dogs , 2012, Mammalian Genome.

[26]  J. Dobson Breed-Predispositions to Cancer in Pedigree Dogs , 2013, ISRN veterinary science.

[27]  T. Marquès-Bonet,et al.  Worldwide patterns of genomic variation and admixture in gray wolves , 2016, Genome research.

[28]  K. Lindblad-Toh,et al.  Efficient mapping of mendelian traits in dogs through genome-wide association , 2007, Nature Genetics.

[29]  Carlos D Bustamante,et al.  Genetic structure in village dogs reveals a Central Asian domestication origin , 2015, Proceedings of the National Academy of Sciences.

[30]  K. Melkersson,et al.  P-709 - Association Between Body Mass Index and Insulin Receptor Substrate-4 (irs-4) Gene Polymorphisms in Patients With Schizophrenia , 2012, European Psychiatry.

[31]  Ilan Gronau,et al.  Genome Sequencing Highlights the Dynamic Early History of Dogs , 2014, PLoS genetics.

[32]  Matthew W. Hahn,et al.  Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication , 2014, Proceedings of the National Academy of Sciences.

[33]  Ptolemaios D. Paxinos,et al.  Inferring Allele Frequency Trajectories from Ancient DNA Indicates That Selection on a Chicken Gene Coincided with Changes in Medieval Husbandry Practices , 2017, Molecular biology and evolution.

[34]  Gary K. Chen,et al.  Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry , 2011, PLoS genetics.

[35]  Daniel G. Bradley,et al.  How Much Is That in Dog Years? The Advent of Canine Population Genomics , 2014, PLoS genetics.

[36]  Thomas J. Nicholas,et al.  Tracking footprints of artificial selection in the dog genome , 2010, Proceedings of the National Academy of Sciences.

[37]  C. London,et al.  Dogs as a Model for Cancer. , 2016, Annual review of animal biosciences.

[38]  M. Webster,et al.  The legacy of domestication: accumulation of deleterious mutations in the dog genome. , 2008, Molecular biology and evolution.

[39]  J. E. Rice,et al.  Multiple and ancient origins of the domestic dog. , 1997, Science.

[40]  Elaine A. Ostrander,et al.  Demographic history, selection and functional diversity of the canine genome , 2017, Nature Reviews Genetics.

[41]  Sara E. Kalla,et al.  Complex disease and phenotype mapping in the domestic dog , 2016, Nature Communications.

[42]  James A. Cuff,et al.  Genome sequence, comparative analysis and haplotype structure of the domestic dog , 2005, Nature.

[43]  S. E. Stewart,et al.  Integrating evolutionary and regulatory information with a multispecies approach implicates genes and pathways in obsessive-compulsive disorder , 2017, Nature Communications.

[44]  Robert K. Wayne,et al.  Evolutionary genomics of dog domestication , 2012, Mammalian Genome.

[45]  Catherine André,et al.  Coat Variation in the Domestic Dog Is Governed by Variants in Three Genes , 2009, Science.

[46]  E. Kirkness,et al.  Extensive and breed-specific linkage disequilibrium in Canis familiaris. , 2004, Genome research.

[47]  N. Mongan,et al.  Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics , 2017, Acta Veterinaria Scandinavica.

[48]  S. Sawyer,et al.  Complete Mitochondrial Genomes of Ancient Canids Suggest a European Origin of Domestic Dogs , 2013, Science.

[49]  A. Araszkiewicz,et al.  Large animals as potential models of human mental and behavioral disorders. , 2017, Psychiatria polska.

[50]  Ilan Gronau,et al.  Demographically-Based Evaluation of Genomic Regions under Selection in Domestic Dogs , 2016, PLoS genetics.

[51]  K. Lindblad-Toh,et al.  Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping , 2011, PLoS genetics.

[52]  J. Våge,et al.  Differential gene expression in brain tissues of aggressive and non-aggressive dogs , 2010, BMC veterinary research.

[53]  E. Mauceli,et al.  Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers , 2015, PLoS genetics.

[54]  A. Boyko,et al.  Population variation revealed high-altitude adaptation of Tibetan mastiffs. , 2014, Molecular biology and evolution.

[55]  Leif Andersson,et al.  Rethinking dog domestication by integrating genetics, archeology, and biogeography , 2012, Proceedings of the National Academy of Sciences.

[56]  E. Kubinyi,et al.  DNA methylation patterns of behavior-related gene promoter regions dissect the gray wolf from domestic dog breeds , 2017, Molecular Genetics and Genomics.

[57]  M. Świtoński,et al.  Confirmation that a deletion in the POMC gene is associated with body weight of Labrador Retriever dogs. , 2017, Research in veterinary science.

[58]  Jacqueline K. White,et al.  Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement , 2012, Nature Genetics.

[59]  Chung-I Wu,et al.  Genetic Convergence in the Adaptation of Dogs and Humans to the High-Altitude Environment of the Tibetan Plateau , 2014, Genome biology and evolution.

[60]  T. Marquès-Bonet,et al.  Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs , 2015, Proceedings of the National Academy of Sciences.

[61]  E. Ostrander,et al.  Whole-genome sequence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic-trait mapping , 2016, Disease Models & Mechanisms.

[62]  Clive D. L. Wynne,et al.  Structural variants in genes associated with human Williams-Beuren syndrome underlie stereotypical hypersociability in domestic dogs , 2017, Science Advances.

[63]  K. Veeramah,et al.  Comparison of village dog and wolf genomes highlights the role of the neural crest in dog domestication , 2018, BMC Biology.

[64]  Brian W Davis,et al.  Whole genome sequencing of canids reveals genomic regions under selection and variants influencing morphology , 2019, Nature Communications.

[65]  T. Famula,et al.  Characteristics of compulsive tail chasing and associated risk factors in Bull Terriers. , 2011, Journal of the American Veterinary Medical Association.

[66]  M. Ceppi,et al.  Cancer incidence in pet dogs: findings of the Animal Tumor Registry of Genoa, Italy. , 2008, Journal of veterinary internal medicine.

[67]  A. Auton,et al.  Candidate genes and functional noncoding variants identified in a canine model of obsessive-compulsive disorder , 2014, Genome Biology.

[68]  E. S. Howell,et al.  The international encyclopedia of dogs , 1971 .

[69]  Lu Wang,et al.  DoGSD: the dog and wolf genome SNP database , 2014, Nucleic Acids Res..

[70]  Jeremiah D. Degenhardt,et al.  Complex population structure in African village dogs and its implications for inferring dog domestication history , 2009, Proceedings of the National Academy of Sciences.

[71]  C. Bustamante,et al.  A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs , 2007, Science.

[72]  P. Wiener,et al.  Genetic Characterization of Dog Personality Traits , 2017, Genetics.

[73]  Jeremiah D. Degenhardt,et al.  A Simple Genetic Architecture Underlies Morphological Variation in Dogs , 2010, PLoS biology.

[74]  Jeremiah D. Degenhardt,et al.  Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication , 2010, Nature.

[75]  J. Sinsheimer,et al.  The concerted impact of domestication and transposon insertions on methylation patterns between dogs and grey wolves , 2016, Molecular ecology.

[76]  P. Moore,et al.  Canine Hemophagocytic Histiocytic Sarcoma: A Proliferative Disorder of CD11d+ Macrophages , 2006, Veterinary pathology.

[77]  K. Lindblad-Toh,et al.  Death of PRDM9 coincides with stabilization of the recombination landscape in the dog genome. , 2012, Genome research.

[78]  R. Kays,et al.  Admixture mapping identifies introgressed genomic regions in North American canids , 2016, Molecular ecology.

[79]  Philipp W. Messer,et al.  Evaluating the performance of selection scans to detect selective sweeps in domestic dogs , 2015, bioRxiv.

[80]  G. Barsh,et al.  Association of an Agouti allele with fawn or sable coat color in domestic dogs , 2005, Mammalian Genome.

[81]  J. Lunec,et al.  Of dogs and men: Comparative biology as a tool for the discovery of novel biomarkers and drug development targets in osteosarcoma , 2012, Pediatric blood & cancer.

[82]  E. Kubinyi,et al.  Lessons from the canine Oxtr gene: populations, variants and functional aspects , 2017, Genes, brain, and behavior.

[83]  O. Thalmann,et al.  Paleogenomic Inferences of Dog Domestication , 2018 .

[84]  Samuel H. Vohr,et al.  Natural Selection and Origin of a Melanistic Allele in North American Gray Wolves , 2018, Molecular biology and evolution.

[85]  B. Wilcox,et al.  Atlas of Dog Breeds of the World , 1995 .

[86]  Aaron J. Sams,et al.  Fine-Scale Resolution of Runs of Homozygosity Reveal Patterns of Inbreeding and Substantial Overlap with Recessive Disease Genotypes in Domestic Dogs , 2018, G3: Genes, Genomes, Genetics.

[87]  A. Clark,et al.  Red fox genome assembly identifies genomic regions associated with tame and aggressive behaviours , 2018, Nature Ecology & Evolution.

[88]  Matthew Oetjens,et al.  Ancient European dog genomes reveal continuity since the Early Neolithic , 2016, Nature Communications.

[89]  K. Lindblad-Toh,et al.  An exome sequencing based approach for genome-wide association studies in the dog , 2017, Scientific Reports.

[90]  K. Lindblad-Toh,et al.  A Mutation in Hairless Dogs Implicates FOXI3 in Ectodermal Development , 2008, Science.

[91]  K. Abe,et al.  Combined Growth Hormone and Thyroid-Stimulating Hormone Deficiency in a Japanese Patient with a Novel Frameshift Mutation in IGSF1 , 2015, Hormone Research in Paediatrics.

[92]  Love Dalén,et al.  Ancient Wolf Genome Reveals an Early Divergence of Domestic Dog Ancestors and Admixture into High-Latitude Breeds , 2015, Current Biology.

[93]  A. Boyko The domestic dog: man's best friend in the genomic era , 2011, Genome Biology.

[94]  G. Barsh,et al.  A β-Defensin Mutation Causes Black Coat Color in Domestic Dogs , 2007, Science.

[95]  K. Lindblad-Toh,et al.  Localization of Canine Brachycephaly Using an Across Breed Mapping Approach , 2010, PloS one.

[96]  E. Ostrander,et al.  Origin, genetic diversity, and genome structure of the domestic dog , 1999, BioEssays : news and reviews in molecular, cellular and developmental biology.

[97]  T. Ratliff,et al.  Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies , 2018, Bladder cancer.

[98]  Yixue Li,et al.  Genomic Analysis Reveals Hypoxia Adaptation in the Tibetan Mastiff by Introgression of the Gray Wolf from the Tibetan Plateau , 2016, Molecular biology and evolution.

[99]  Erik Axelsson,et al.  Amy2B copy number variation reveals starch diet adaptations in ancient European dogs , 2016, Royal Society Open Science.

[100]  E. Ostrander,et al.  Commonalities in Development of Pure Breeds and Population Isolates Revealed in the Genome of the Sardinian Fonni's Dog , 2016, Genetics.

[101]  E. Ostrander,et al.  Genetic selection of athletic success in sport-hunting dogs , 2018, Proceedings of the National Academy of Sciences.

[102]  Asan,et al.  Altitude adaptation in Tibet caused by introgression of Denisovan-like DNA , 2014, Nature.

[103]  F. Galibert,et al.  Epidemiology, pathology, and genetics of histiocytic sarcoma in the Bernese mountain dog breed. , 2009, The Journal of heredity.

[104]  Holly C. Beale,et al.  Derived variants at six genes explain nearly half of size reduction in dog breeds , 2013, Genome research.

[105]  J. Lundeberg,et al.  mtDNA Data Indicate a Single Origin for Dogs South of Yangtze River, Less Than 16,300 Years Ago, from Numerous Wolves , 2009, Molecular biology and evolution.

[106]  Chaochun Wei,et al.  Whole-genome sequencing of six dog breeds from continuous altitudes reveals adaptation to high-altitude hypoxia , 2014, Genome research.

[107]  P. Howell At Home and Astray: The Domestic Dog in Victorian Britain , 2015 .

[108]  Jue Ruan,et al.  Structural variation during dog domestication: insights from gray wolf and dhole genomes , 2018, National science review.

[109]  Guo-Dong Wang,et al.  Out of southern East Asia: the natural history of domestic dogs across the world , 2015, Cell Research.

[110]  S. Blott,et al.  Trends in genetic diversity for all Kennel Club registered pedigree dog breeds , 2015, Canine Genetics and Epidemiology.

[111]  C. Drögemüller,et al.  A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs. , 2007, The Journal of heredity.

[112]  M. Grados,et al.  Genetics of obsessive–compulsive disorder: a research update , 2007, Expert review of neurotherapeutics.

[113]  E. Ostrander,et al.  Domestic dogs and cancer research: a breed-based genomics approach. , 2014, ILAR journal.

[114]  E. Ostrander,et al.  Genomic Analyses Reveal the Influence of Geographic Origin, Migration, and Hybridization on Modern Dog Breed Development. , 2017, Cell reports.

[115]  Ya-ping Zhang,et al.  Identifying molecular signatures of hypoxia adaptation from sex chromosomes: A case for Tibetan Mastiff based on analyses of X chromosome , 2016, Scientific Reports.

[116]  R. Wayne,et al.  Phylogenetic relationships, evolution, and genetic diversity of the domestic dog. , 1999, The Journal of heredity.

[117]  C. Hänni,et al.  Dogs accompanied humans during the Neolithic expansion into Europe , 2018, Biology Letters.

[118]  L. Kruglyak,et al.  Unleashing the canine genome. , 2000, Genome research.