Abstract: To date, genome-scale analyses in the domestic horse have been limited by suboptimal single nucleotide polymorphism (SNP) density and uneven genomic coverage of the current SNP genotyping arrays. The recent availability of whole genome sequences has created the opportunity to develop a next generation, high-density equine SNP array. Using whole genome sequence from 153 individuals representing 24 distinct breeds collated by the equine genomics community, we cataloged over 23 million de novo discovered genetic variants. Leveraging genotype data from individuals with both whole genome sequence, and genotypes from lower-density, legacy SNP arrays, a subset of ~5 million high-quality, high-density array candidate SNPs were selected based on breed representation and uniform spacing across the genome. Considering probe design recommendations from a commercial vendor (Affymetrix, now Thermo Fisher Scientific) a set of ~2 million SNPs were selected for a next-generation high-density SNP chip (MNEc2M). Genotype data were generated using the MNEc2M array from a cohort of 332 horses from 20 breeds and a lower-density array, consisting of ~670 thousand SNPs (MNEc670k), was designed for genotype imputation. Here, we document the steps taken to design both the MNEc2M and MNEc670k arrays, report genomic and technical properties of these genotyping platforms, and demonstrate the imputation capabilities of these tools for the domestic horse.
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This research focuses on the development of a genotyping array to identify approximately 2 million genetic variants across 24 horse breeds using 670 thousand single nucleotide polymorphisms (SNPs).
Introduction
Genome-scale analyses of domestic horses have been previously limited due to inadequacies in single nucleotide polymorphism (SNP) density and inconsistency in genomic coverage of the available SNP genotyping arrays.
The recent availability of whole genome sequences paves the way for the development of a next-generation, high-density equine SNP array.
Development of High-Density Equine SNP Array
Using the whole genome sequence data of 153 individuals from 24 different horse breeds, researchers identified over 23 million de novo genetic variants.
The team then used genotype data from individuals who had both whole genome sequence data and genotypes from lower-density, older SNP arrays to identify a set of approximately 5 million high-quality candidate SNPs. Selection was based on breed representation and uniform spacing across the genome.
Final SNP Selection
Guided by probe design recommendations from commercial vendor Affymetrix, now Thermo Fisher Scientific, the researchers narrowed down a set of about 2 million SNPs to generate a next-generation high-density SNP chip, referred to as MNEc2M.
They also designed a lower-density array, consisting of approximately 670 thousand SNPs, referred to as MNEc670k, intended for genotype imputation.
Testing and Validation of the MNEc2M and MNEc670k Arrays
The researchers then tested these new arrays by generating genotype data from a cohort of 332 horses from 20 breeds.
Their research documents the design steps taken for both the MNEc2M and MNEc670k arrays and reports on the genomic and technical properties of these genotyping platforms.
They also demonstrate the potential of these new genotyping arrays in improving genotype imputation, a statistical method used to predict unknown genotypes, for domestic horses.
Cite This Article
APA
Schaefer RJ, Schubert M, Bailey E, Bannasch DL, Barrey E, Bar-Gal GK, Brem G, Brooks SA, Distl O, Fries R, Finno CJ, Gerber V, Haase B, Jagannathan V, Kalbfleisch T, Leeb T, Lindgren G, Lopes MS, Mach N, da Câmara Machado A, MacLeod JN, McCoy A, Metzger J, Penedo C, Polani S, Rieder S, Tammen I, Tetens J, Thaller G, Verini-Supplizi A, Wade CM, Wallner B, Orlando L, Mickelson JR, McCue ME.
(2017).
Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds.
BMC Genomics, 18(1), 565.
https://doi.org/10.1186/s12864-017-3943-8
Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
Schubert, Mikkel
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.
Bailey, Ernest
Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Bannasch, Danika L
School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Barrey, Eric
Unité de Génétique Animale et Biologie Intégrative- UMR1313, INRA, Université Paris-Saclay, AgroParisTech, 78350, Jouy-en-Josas, France.
Bar-Gal, Gila Kahila
The Robert H. Smith Faculty of Agriculture, Food and Environment, The Koret School of Veterinary Medicine, The Hebrew University, 76100, Rehovot, Israel.
Brem, Gottfried
Institute of Animal Breeding and Genetics, Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Vienna, Austria.
Brooks, Samantha A
Department of Animal Science, University of Florida, Gainesville, FL, USA.
Distl, Ottmar
Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Hannover, Germany.
Fries, Ruedi
Lehrstuhl für Tierzucht der Technischen Universität München, Liesel-Beckmann-Strasse 1, 85354, Freising, Germany.
Finno, Carrie J
School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Gerber, Vinzenz
Swiss Institute of Equine Medicine, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, and Agroscope, Länggassstrasse 124, 3001, Bern, Switzerland.
Haase, Bianca
School of Life and Environmental Sciences, Faculty of Veterinary Science, University of Sydney, Regimental Drive, B19-301 RMC Gunn, Sydney, NSW, 2006, Australia.
Jagannathan, Vidhya
Institute of Genetics, University of Bern, 3001, Bern, Switzerland.
Kalbfleisch, Ted
Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
Leeb, Tosso
Institute of Genetics, University of Bern, 3001, Bern, Switzerland.
Lindgren, Gabriella
Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Lopes, Maria Susana
Biotechnology Centre of Azores, University of Azores, Angra do heroísmo, Portugal.
Mach, Núria
Unité de Génétique Animale et Biologie Intégrative- UMR1313, INRA, Université Paris-Saclay, AgroParisTech, 78350, Jouy-en-Josas, France.
da Câmara Machado, Artur
Biotechnology Centre of Azores, University of Azores, Angra do heroísmo, Portugal.
MacLeod, James N
Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
McCoy, Annette
Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Champaign, IL, 61802, USA.
Metzger, Julia
Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Hannover, Germany.
Penedo, Cecilia
Veterinary Genetics Laboratory, University of California Davis, Davis, CA, USA.
Polani, Sagi
The Robert H. Smith Faculty of Agriculture, Food and Environment, The Koret School of Veterinary Medicine, The Hebrew University, 76100, Rehovot, Israel.
Rieder, Stefan
Agroscope, Swiss National Stud Farm, 1580, Avenches, Switzerland.
Tammen, Imke
School of Life and Environmental Sciences, Faculty of Veterinary Science, University of Sydney, Regimental Drive, B19-301 RMC Gunn, Sydney, NSW, 2006, Australia.
Tetens, Jens
Institute of Animal Breeding and Husbandry, Christian-Albrechts-University Kiel, Hermann-Rodewald-Strasse 6, 24098, Kiel, Germany.
Department of Animal Sciences, Functional Breeding Group, Georg-August University Göttingen, Burckhardtweg 2, 37077, Göttingen, Germany.
Thaller, Georg
Institute of Animal Breeding and Husbandry, Christian-Albrechts-University Kiel, Hermann-Rodewald-Strasse 6, 24098, Kiel, Germany.
Verini-Supplizi, Andrea
Department of Veterinary Medicine - Sport Horse Research Centre, University of Perugia, Perugia, Italy.
Wade, Claire M
School of Life and Environmental Sciences, Faculty of Veterinary Science, University of Sydney, Regimental Drive, B19-301 RMC Gunn, Sydney, NSW, 2006, Australia.
Wallner, Barbara
Institute of Animal Breeding and Genetics, Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Vienna, Austria.
Orlando, Ludovic
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.
Laboratoire d'Anthropobiologie Moléculaire et d'Imagerie de Synthèse, CNRS UMR 5288, Université de Toulouse, Université Paul Sabatier, 31000, Toulouse, France.
Mickelson, James R
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
McCue, Molly E
Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA. mccų@umn.edu.
ETHICS APPROVAL AND CONSENT TO PARTICIPATE: DNA samples were previously collected with approval from the Animal Care and Use Committees at the respective institutions. All animal work was performed in accordance and with approval from international and national governing bodies at the institutions where the samples were collected (University of Minnesota Institutional Animal Care and Use Committee (IACUC); University of California, Davis Institutional Animal Care and Use Committee (protocol #17491); University of Kentucky Institutional Animal Care and Use Committee (IACUC); Ethics Committee for Animal Experiments in Uppsala, Sweden (Number C121/14); Institutional animal care and use committee at Cornell University (protocol 2008-0121); University of California, Davis IACUC 19205; Hebrew University’s approval number AG-23476-07; Institutional Animal Care and Use Committee (IACUC), the Lower Saxony state veterinary office- registration number 11A 160/7221.3-2.1-015/11, 8.84-02.05.20.12.066; University of Sydney Animal Ethics Committee: AEC APPROVAL NUMBER: N00/9-2009/3/5109; permit no. BE75/16, veterinary service of the Canton of Bern; Institutional ethics committee of the University of Veterinary Medicine Vienna Good Scientific Practice guidelines and national legislation; Italian Ministry of Agricultural, Food and Forestry Policies (Mipaaf); Ethical Committee of the Canton of Bern (BE33/07, BE58/10 and BE10/13)) No commercial animals were used in this study. Written informed client consent describing the purpose and duration of the study, procedures, potential risks and benefits and containing study contact information were obtained from private owners. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
This article includes 49 references
Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blöcker H, Distl O, Edgar RC, Garber M, Leeb T, Mauceli E, MacLeod JN, Penedo MC, Raison JM, Sharpe T, Vogel J, Andersson L, Antczak DF, Biagi T, Binns MM, Chowdhary BP, Coleman SJ, Della Valle G, Fryc S, Guérin G, Hasegawa T, Hill EW, Jurka J, Kiialainen A, Lindgren G, Liu J, Magnani E, Mickelson JR, Murray J, Nergadze SG, Onofrio R, Pedroni S, Piras MF, Raudsepp T, Rocchi M, Røed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvänen AC, Tozaki T, Valberg SJ, Vaudin M, White JR, Zody MC, Lander ES, Lindblad-Toh K. Genome sequence, comparative analysis, and population genetics of the domestic horse.. Science 2009 Nov 6;326(5954):865-7.
Schubert M, Jónsson H, Chang D, Der Sarkissian C, Ermini L, Ginolhac A, Albrechtsen A, Dupanloup I, Foucal A, Petersen B, Fumagalli M, Raghavan M, Seguin-Orlando A, Korneliussen TS, Velazquez AM, Stenderup J, Hoover CA, Rubin CJ, Alfarhan AH, Alquraishi SA, Al-Rasheid KA, MacHugh DE, Kalbfleisch T, MacLeod JN, Rubin EM, Sicheritz-Ponten T, Andersson L, Hofreiter M, Marques-Bonet T, Gilbert MT, Nielsen R, Excoffier L, Willerslev E, Shapiro B, Orlando L. Prehistoric genomes reveal the genetic foundation and cost of horse domestication.. Proc Natl Acad Sci U S A 2014 Dec 30;111(52):E5661-9.
Jónsson H, Schubert M, Seguin-Orlando A, Ginolhac A, Petersen L, Fumagalli M, Albrechtsen A, Petersen B, Korneliussen TS, Vilstrup JT, Lear T, Myka JL, Lundquist J, Miller DC, Alfarhan AH, Alquraishi SA, Al-Rasheid KA, Stagegaard J, Strauss G, Bertelsen MF, Sicheritz-Ponten T, Antczak DF, Bailey E, Nielsen R, Willerslev E, Orlando L. Speciation with gene flow in equids despite extensive chromosomal plasticity.. Proc Natl Acad Sci U S A 2014 Dec 30;111(52):18655-60.
Petersen JL, Mickelson JR, Cothran EG, Andersson LS, Axelsson J, Bailey E, Bannasch D, Binns MM, Borges AS, Brama P, da Câmara Machado A, Distl O, Felicetti M, Fox-Clipsham L, Graves KT, Guérin G, Haase B, Hasegawa T, Hemmann K, Hill EW, Leeb T, Lindgren G, Lohi H, Lopes MS, McGivney BA, Mikko S, Orr N, Penedo MC, Piercy RJ, Raekallio M, Rieder S, Røed KH, Silvestrelli M, Swinburne J, Tozaki T, Vaudin M, M Wade C, McCue ME. Genetic diversity in the modern horse illustrated from genome-wide SNP data.. PLoS One 2013;8(1):e54997.
Schubert M, Ermini L, Der Sarkissian C, Jónsson H, Ginolhac A, Schaefer R, Martin MD, Fernández R, Kircher M, McCue M, Willerslev E, Orlando L. Characterization of ancient and modern genomes by SNP detection and phylogenomic and metagenomic analysis using PALEOMIX.. Nat Protoc 2014 May;9(5):1056-82.
Orlando L, Ginolhac A, Zhang G, Froese D, Albrechtsen A, Stiller M, Schubert M, Cappellini E, Petersen B, Moltke I, Johnson PL, Fumagalli M, Vilstrup JT, Raghavan M, Korneliussen T, Malaspinas AS, Vogt J, Szklarczyk D, Kelstrup CD, Vinther J, Dolocan A, Stenderup J, Velazquez AM, Cahill J, Rasmussen M, Wang X, Min J, Zazula GD, Seguin-Orlando A, Mortensen C, Magnussen K, Thompson JF, Weinstock J, Gregersen K, Røed KH, Eisenmann V, Rubin CJ, Miller DC, Antczak DF, Bertelsen MF, Brunak S, Al-Rasheid KA, Ryder O, Andersson L, Mundy J, Krogh A, Gilbert MT, Kjær K, Sicheritz-Ponten T, Jensen LJ, Olsen JV, Hofreiter M, Nielsen R, Shapiro B, Wang J, Willerslev E. Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse.. Nature 2013 Jul 4;499(7456):74-8.
Der Sarkissian C, Ermini L, Schubert M, Yang MA, Librado P, Fumagalli M, Jónsson H, Bar-Gal GK, Albrechtsen A, Vieira FG, Petersen B, Ginolhac A, Seguin-Orlando A, Magnussen K, Fages A, Gamba C, Lorente-Galdos B, Polani S, Steiner C, Neuditschko M, Jagannathan V, Feh C, Greenblatt CL, Ludwig A, Abramson NI, Zimmermann W, Schafberg R, Tikhonov A, Sicheritz-Ponten T, Willerslev E, Marques-Bonet T, Ryder OA, McCue M, Rieder S, Leeb T, Slatkin M, Orlando L. Evolutionary Genomics and Conservation of the Endangered Przewalski's Horse.. Curr Biol 2015 Oct 5;25(19):2577-83.
Librado P, Der Sarkissian C, Ermini L, Schubert M, Jónsson H, Albrechtsen A, Fumagalli M, Yang MA, Gamba C, Seguin-Orlando A, Mortensen CD, Petersen B, Hoover CA, Lorente-Galdos B, Nedoluzhko A, Boulygina E, Tsygankova S, Neuditschko M, Jagannathan V, Thèves C, Alfarhan AH, Alquraishi SA, Al-Rasheid KA, Sicheritz-Ponten T, Popov R, Grigoriev S, Alekseev AN, Rubin EM, McCue M, Rieder S, Leeb T, Tikhonov A, Crubézy E, Slatkin M, Marques-Bonet T, Nielsen R, Willerslev E, Kantanen J, Prokhortchouk E, Orlando L. Tracking the origins of Yakutian horses and the genetic basis for their fast adaptation to subarctic environments.. Proc Natl Acad Sci U S A 2015 Dec 15;112(50):E6889-97.
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data.. Genome Res 2010 Sep;20(9):1297-303.
Li H. 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.
Raghavan V, Bollmann P, Jung GS. A critical investigation of recall and precision as measures of retrieval system performance.. ACM Trans Inf Syst 1989;7:205–29.
Saito T, Rehmsmeier M. The precision-recall plot is more informative than the ROC plot when evaluating binary classifiers on imbalanced datasets.. PLoS One 2015;10(3):e0118432.
DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, Philippakis AA, del Angel G, Rivas MA, Hanna M, McKenna A, Fennell TJ, Kernytsky AM, Sivachenko AY, Cibulskis K, Gabriel SB, Altshuler D, Daly MJ. A framework for variation discovery and genotyping using next-generation DNA sequencing data.. Nat Genet 2011 May;43(5):491-8.
Liu G, Wang Y, Wong L. FastTagger: an efficient algorithm for genome-wide tag SNP selection using multi-marker linkage disequilibrium.. BMC Bioinformatics 2010 Jan 29;11:66.
von Hippel PT. Mean, Median, and Skew: Correcting a Textbook Rule.. J. Stat. Educ. American Statistical Association 2005;13.
Kranis A, Gheyas AA, Boschiero C, Turner F, Yu L, Smith S, Talbot R, Pirani A, Brew F, Kaiser P, Hocking PM, Fife M, Salmon N, Fulton J, Strom TM, Haberer G, Weigend S, Preisinger R, Gholami M, Qanbari S, Simianer H, Watson KA, Woolliams JA, Burt DW. Development of a high density 600K SNP genotyping array for chicken.. BMC Genomics 2013 Jan 28;14:59.
Groenen MAM. Development of a high-density Axiom® porcine genotyping array to meet research and commercial needs.. Plant Anim. Genome XXIII Conf. San Diego, CA: Plant & Animal Genome XXIII Conference; 2015.
Rincon G, Weber KL, Eenennaam AL, Golden BL, Medrano JF. Hot topic: performance of bovine high-density genotyping platforms in Holsteins and Jerseys.. J Dairy Sci 2011 Dec;94(12):6116-21.
Salomón-Torres R, González-Vizcarra VM, Medina-Basulto GE, Montaño-Gómez MF, Mahadevan P, Yaurima-Basaldúa VH, Villa-Angulo C, Villa-Angulo R. Genome-wide identification of copy number variations in Holstein cattle from Baja California, Mexico, using high-density SNP genotyping arrays.. Genet Mol Res 2015 Oct 2;14(4):11848-59.
Salomon-Torres R, Villa-Angulo R, Villa-Angulo C. Analysis of copy number variations in Mexican Holstein cattle using axiom genome-wide Bos 1 array.. Genom Data 2016 Mar;7:97-100.
Romé H, Varenne A, Hérault F, Chapuis H, Alleno C, Dehais P, Vignal A, Burlot T, Le Roy P. GWAS analyses reveal QTL in egg layers that differ in response to diet differences.. Genet Sel Evol 2015 Oct 19;47:83.
Lu D, Akanno EC, Crowley JJ, Schenkel F, Li H, De Pauw M, Moore SS, Wang Z, Li C, Stothard P, Plastow G, Miller SP, Basarab JA. Accuracy of genomic predictions for feed efficiency traits of beef cattle using 50K and imputed HD genotypes.. J Anim Sci 2016 Apr;94(4):1342-53.
Li G, Li D, Yang N, Qu L, Hou Z, Zheng J, Xu G, Chen S. A genome-wide association study identifies novel single nucleotide polymorphisms associated with dermal shank pigmentation in chickens.. Poult Sci 2014 Dec;93(12):2983-7.
Smit AFA, Hubley R, Green P. RepeatMasker Open-4.0.2013-2015. .
Browning SR, Browning BL. Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering.. Am J Hum Genet 2007 Nov;81(5):1084-97.
Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, Handsaker RE, Lunter G, Marth GT, Sherry ST, McVean G, Durbin R. The variant call format and VCFtools.. Bioinformatics 2011 Aug 1;27(15):2156-8.