CoChat
Sign Up
Cited by 2Genetic and phenotypic traits in livestockHuman-Animal Interaction StudiesGenetic Mapping and Diversity in Plants and Animals

Systematically identifying genetic signatures including novel SNP-clusters, nonsense variants, frame-shift INDELs, and long STR expansions that potentially link to unknown phenotypes existing in dog breeds

Open access
Li, Zicheng, Wang, Zuoheng, Chen, Zhiyuan, Voegeli, Heidi, Lichtman, Judith H., Smith, Peter, Liu, Ju, DeWan, Andrew T. +1 more·2023·BMC Genomics
DOI 10.1186/s12864-023-09390-6PMC PMC10240460
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: In light of previous studies that profiled breed-specific traits or used genome-wide association studies to refine loci associated with characteristic morphological features in dogs, the field has gained tremendous genetic insights for known dog traits observed among breeds. Here we aim to address the question from a reserve perspective: whether there are breed-specific genotypes that may underlie currently unknown phenotypes. This study provides a complete set of breed-specific genetic signatures (BSGS). Several novel BSGS with significant protein-altering effects were highlighted and validated. Results: Using the next generation whole-genome sequencing technology coupled with unsupervised machine learning for pattern recognitions, we constructed and analyzed a high-resolution sequence map for 76 breeds of 412 dogs. Genomic structures including novel single nucleotide polymorphisms (SNPs), SNP clusters, insertions, deletions (INDELs) and short tandem repeats (STRs) were uncovered mutually exclusively among breeds. We also partially validated some novel nonsense variants by Sanger sequencing with additional dogs. Four novel nonsense BSGS were found in the Bernese Mountain Dog, Samoyed, Bull Terrier, and Basset Hound, respectively. Four INDELs resulting in either frame-shift or codon disruptions were found in the Norwich Terrier, Airedale Terrier, Chow Chow and Bernese Mountain Dog, respectively. A total of 15 genomic regions containing three types of BSGS (SNP-clusters, INDELs and STRs) were identified in the Akita, Alaskan Malamute, Chow Chow, Field Spaniel, Keeshond, Shetland Sheepdog and Sussex Spaniel, in which Keeshond and Sussex Spaniel each carried one amino-acid changing BSGS in such regions. Conclusion: Given the strong relationship between human and dog breed-specific traits, this study might be of considerable interest to researchers and all. Novel genetic signatures that can differentiate dog breeds were uncovered. Several functional genetic signatures might indicate potentially breed-specific unknown phenotypic traits or disease predispositions. These results open the door for further investigations. Importantly, the computational tools we developed can be applied to any dog breeds as well as other species. This study will stimulate new thinking, as the results of breed-specific genetic signatures may offer an overarching relevance of the animal models to human health and disease.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s12864-023-09390-6

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Canine genetic testing panels of SNP clusters, nonsense variants, frame-shift indels, and long STR expansions can distinguish between popular dog breeds.

    “Canine genetic testing panels of SNP clusters, nonsense variants, frame-shift insertions or deletions (indels), and long STR expansions can distinguish between popular dog breeds, which is important for toxicology studies [65].”

    From Genetic Insights into the Economic Toll of Cell Line Misidentification: A Comprehensive Review (2026) · cites this paper as [65]

    The Discussion (page unavailable) reports breed-specific SNP, INDEL, and STR signatures that distinguish breeds, and the Results identify breed-specific nonsense and frame-shift variants. The paper describes a genomic signature catalog, not a tested canine genetic-testing panel; it also does not establish the stated importance for toxicology studies. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 42

  1. [1]Larson G Karlsson EK Perri A Webster MT Ho SY Peters J Stahl PW Piper PJ Lingaas F Fredholm M Rethinking dog domestication by integrating genetics, archeology, and biogeography Proc Natl Acad Sci 2012 109 23 8878 8883 10.1073/pnas.1203005109 22615366 PMC3384140 · DOI · Paper page
  2. [2]Lahtinen M Clinnick D Mannermaa K Salonen JS Viranta S Excess protein enabled dog domestication during severe Ice Age winters Sci Rep 2021 11 1 1 5 10.1038/s41598-020-78214-4 33414490 PMC7790815 · DOI
  3. [3]Marsden CD Ortega-Del Vecchyo D O’Brien DP Taylor JF Ramirez O Vilà C Marques-Bonet T Schnabel RD Wayne RK Lohmueller KE Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs Proc Natl Acad Sci 2016 113 1 152 157 10.1073/pnas.1512501113 26699508 PMC4711855 · DOI · Paper page
  4. [4]Wayne RK Vonholdt BM Evolutionary genomics of dog domestication Mamm Genome 2012 23 1 3 18 10.1007/s00335-011-9386-7 22270221 · DOI
  5. [5]Parker HG Dreger DL Rimbault M Davis BW Mullen AB Carpintero-Ramirez G Ostrander EA Genomic analyses reveal the influence of geographic origin, migration, and hybridization on modern dog breed development Cell Rep 2017 19 4 697 708 10.1016/j.celrep.2017.03.079 28445722 PMC5492993 · DOI
  6. [6]Gordon D Corwin M Mellersh C Ostrander E Ott J Establishing appropriate genome-wide significance levels for canine linkage analyses J Hered 2003 94 1 1 7 10.1093/jhered/esg009 12692155 · DOI
  7. [7]Vonholdt BM Pollinger JP Lohmueller KE Han E Parker HG Quignon P Degenhardt JD Boyko AR Earl DA Auton A Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication Nature 2010 464 7290 898 902 10.1038/nature08837 20237475 PMC3494089 · DOI
  8. [8]Vaysse A Ratnakumar A Derrien T Axelsson E Rosengren Pielberg G Sigurdsson S Fall T Seppälä EH Hansen MS Lawley CT Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping PLoS Genet 2011 7 10 e1002316 10.1371/journal.pgen.1002316 22022279 PMC3192833 · DOI
  9. [9]Karlsson EK Lindblad-Toh K Leader of the pack: gene mapping in dogs and other model organisms Nat Rev Genet 2008 9 9 713 725 10.1038/nrg2382 18714291 · DOI
  10. [10]Parker HG Ostrander EA Canine genomics and genetics: running with the pack PLoS Genet 2005 1 5 e58 10.1371/journal.pgen.0010058 16311623 PMC1287952 · DOI
  11. [11]Davis BW Ostrander EA Domestic dogs and cancer research: a breed-based genomics approach ILAR J 2014 55 1 59 68 10.1093/ilar/ilu017 24936030 PMC4158346 · DOI
  12. [12]Lin L Faraco J Li R Kadotani H Rogers W Lin X Qiu X de Jong PJ Nishino S Mignot E The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene Cell 1999 98 3 365 376 10.1016/S0092-8674(00)81965-0 10458611 · DOI · Paper page
  13. [13]Karlsson EK Sigurdsson S Ivansson E Thomas R Elvers I Wright J Howald C Tonomura N Perloski M Swofford R Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B Genome Biol 2013 14 12 1 16 10.1186/gb-2013-14-12-r132 PMC4053774 24330828 · DOI
  14. [14]Adams V Evans K Sampson J Wood J Methods and mortality results of a health survey of purebred dogs in the UK J Small Anim Pract 2010 51 10 512 524 10.1111/j.1748-5827.2010.00974.x 21029096 · DOI
  15. [15]Wang Z Kuhr CS Allen JM Blankinship M Gregorevic P Chamberlain JS Tapscott SJ Storb R Sustained AAV-mediated dystrophin expression in a canine model of Duchenne muscular dystrophy with a brief course of immunosuppression Mol Ther 2007 15 6 1160 1166 10.1038/sj.mt.6300161 17426713 · DOI
  16. [16]Kornegay JN Li J Bogan JR Bogan DJ Chen C Zheng H Wang B Qiao C Howard JF Jr Xiao X Widespread muscle expression of an AAV9 human mini-dystrophin vector after intravenous injection in neonatal dystrophin-deficient dogs Mol Ther 2010 18 8 1501 1508 10.1038/mt.2010.94 20517298 PMC2927072 · DOI
  17. [17]Petersen-Jones SM Komáromy AM Dog models for blinding inherited retinal dystrophies Hum Gene Ther Clin Dev 2015 26 1 15 26 10.1089/humc.2014.155 25671556 PMC4442585 · DOI
  18. [18]Amoasii L Hildyard JC Li H Sanchez-Ortiz E Mireault A Caballero D Harron R Stathopoulou T-R Massey C Shelton JM Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy Science 2018 362 6410 86 91 10.1126/science.aau1549 30166439 PMC6205228 · DOI · Paper page
  19. [19]Plassais J Kim J Davis BW Karyadi DM Hogan AN Harris AC Decker B Parker HG Ostrander EA Whole genome sequencing of canids reveals genomic regions under selection and variants influencing morphology Nat Commun 2019 10 1 1 14 10.1038/s41467-019-09373-w 30940804 PMC6445083 · DOI
  20. [20]Hayward JJ Castelhano MG Oliveira KC Corey E Balkman C Baxter TL Casal ML Center SA Fang M Garrison SJ Complex disease and phenotype mapping in the domestic dog Nat Commun 2016 7 1 1 11 10.1038/ncomms10460 PMC4735900 26795439 · DOI
  21. [21]Plassais J Rimbault M Williams FJ Davis BW Schoenebeck JJ Ostrander EA Analysis of large versus small dogs reveals three genes on the canine X chromosome associated with body weight, muscling and back fat thickness PLoS Genet 2017 13 3 e1006661 10.1371/journal.pgen.1006661 28257443 PMC5357063 · DOI
  22. [22]Schoenebeck JJ Ostrander EA The genetics of canine skull shape variation Genetics 2013 193 2 317 325 10.1534/genetics.112.145284 23396475 PMC3567726 · DOI
  23. [23]Clark LA Wahl JM Rees CA Murphy KE Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog Proc Natl Acad Sci 2006 103 5 1376 1381 10.1073/pnas.0506940103 16407134 PMC1360527 · DOI
  24. [24]Slavney AJ Kawakami T Jensen MK Nelson TC Sams AJ Boyko AR Five genetic variants explain over 70% of hair coat pheomelanin intensity variation in purebred and mixed breed domestic dogs PLoS One 2021 16 5 e0250579 10.1371/journal.pone.0250579 34043658 PMC8158882 · DOI
  25. [25]Karlsson EK Baranowska I Wade CM Salmon Hillbertz NH Zody MC Anderson N Biagi TM Patterson N Pielberg GR Kulbokas EJ Efficient mapping of mendelian traits in dogs through genome-wide association Nat Genet 2007 39 11 1321 1328 10.1038/ng.2007.10 17906626 · DOI
  26. [26]Kim J Williams FJ Dreger DL Plassais J Davis BW Parker HG Ostrander EA Genetic selection of athletic success in sport-hunting dogs Proc Natl Acad Sci 2018 115 30 E7212 E7221 10.1073/pnas.1800455115 29970415 PMC6065024 · DOI
  27. [27]Friedrich J Strandberg E Arvelius P Sánchez-Molano E Pong-Wong R Hickey JM Haskell MJ Wiener P Genetic dissection of complex behaviour traits in German Shepherd dogs Heredity 2019 123 6 746 758 10.1038/s41437-019-0275-2 31611599 PMC6834583 · DOI
  28. [28]Shan S Xu F Brenig B Genome-wide association studies reveal neurological genes for dog herding, predation, temperament, and trainability traits Front Vet Sci 2021 8 693290 10.3389/fvets.2021.693290 34368281 PMC8335642 · DOI
  29. [29]Persson M Roth L Johnsson M Wright D Jensen P Human-directed social behaviour in dogs shows significant heritability Genes Brain Behav 2015 14 4 337 344 10.1111/gbb.12194 25703740 · DOI
  30. [31]Morrill K Hekman J Li X McClure J Logan B Goodman L Gao M Dong Y Alonso M Carmichael E Ancestry-inclusive dog genomics challenges popular breed stereotypes Science 2022 376 6592 eabk0639 10.1126/science.abk0639 35482869 PMC9675396 · DOI
  31. [32]Friedrich J Talenti A Arvelius P Strandberg E Haskell MJ Wiener P Unravelling selection signatures in a single dog breed suggests recent selection for morphological and behavioral traits Adv Genet 2020 1 1 e10024 36619250 PMC9744541
  32. [33]Zhang D Ma S Wang L Ma H Wang W Xia J Liu D Min pig skeletal muscle response to cold stress PLoS One 2022 17 9 e0274184 10.1371/journal.pone.0274184 36155652 PMC9512212 · DOI
  33. [34]De Lange KM Moutsianas L Lee JC Lamb CA Luo Y Kennedy NA Jostins L Rice DL Gutierrez-Achury J Ji S-G Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease Nat Genet 2017 49 2 256 261 10.1038/ng.3760 28067908 PMC5289481 · DOI · Paper page
  34. [35]Qin W Rong X Yu C Jia P Yang J Zhou G Knockout of SLAMF8 attenuates collagen-induced rheumatoid arthritis in mice through inhibiting TLR4/NF-κB signaling pathway Int Immunopharmacol 2022 107 108644 10.1016/j.intimp.2022.108644 35259711 · DOI
  35. [36]Matsuura K Kobayashi S Konno K Yamasaki M Horiuchi T Senda T Hayashi T Satoh K Arima-Yoshida F Iwasaki K SIPA1L1/SPAR1 interacts with the neurabin family of proteins and is involved in GPCR signaling J Neurosci 2022 42 12 2448 2473 10.1523/JNEUROSCI.0569-21.2022 35121636 PMC8944240 · DOI
  36. [37]Andrews S FastQC: a quality control tool for high throughput sequence data 2010 Cambridge Babraham Bioinformatics, Babraham Institute
  37. [38]Bolger AM Lohse M Usadel B Trimmomatic: a flexible trimmer for Illumina sequence data Bioinformatics 2014 30 15 2114 2120 10.1093/bioinformatics/btu170 24695404 PMC4103590 · DOI · Paper page
  38. [39]Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv preprint arXiv:13033997. 2013.
  39. [40]Li H Handsaker B Wysoker A Fennell T Ruan J Homer N Marth G Abecasis G Durbin R The sequence alignment/map format and SAMtools Bioinformatics 2009 25 16 2078 2079 10.1093/bioinformatics/btp352 19505943 PMC2723002 · DOI · Paper page
  40. [41]McKenna A Hanna M Banks E Sivachenko A Cibulskis K Kernytsky A Garimella K Altshuler D Gabriel S Daly M The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data Genome Res 2010 20 9 1297 1303 10.1101/gr.107524.110 20644199 PMC2928508 · DOI · Paper page
  41. [42]Cingolani P Platts A Wang LL Coon M Nguyen T Wang L Land SJ Lu X Ruden DM A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3 Fly 2012 6 2 80 92 10.4161/fly.19695 22728672 PMC3679285 · DOI · Paper page
  42. [43]Revell LJ phytools: an R package for phylogenetic comparative biology (and other things) Methods Ecol Evol 2012 2 217 223 10.1111/j.2041-210X.2011.00169.x · DOI

Cited by

Sorted by citations

Authors
Li, Z., Wang, Z., Chen, Z., Voegeli, H., Lichtman, J. H., Smith, P., Liu, J., DeWan, A. T., & Hoh, J.
Affiliations
  • Yale University (US)
  • Shandong Provincial QianFoShan Hospital (CN)
Corresponding author
  • Li, Zicheng
  • Hoh, Josephine
ORCID
Venue
BMC Genomics
Publisher
Springer Science and Business Media LLC
Published
2023-06-05
Volume
24
Issue
1
Pages
302-302
ISSN
1471-2164 (ISSN-L)
DOI
10.1186/s12864-023-09390-6
PMC
PMC10240460
OpenAlex
W4379470561
Cited by
2
References
1
Citations by year
2026: 1 · 2025: 1
FWCI
0.33
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Genomics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Yale School of Medicine
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Human-Animal Interaction Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords
dog breeds, single nucleotide polymorphisms, nonsense mutation, short tandem repeat expansions, disease susceptibility, comparative genomics
MeSH terms
Plant Breeding, Animals, Dogs, Genotype, Humans, Phenotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review