Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds.
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.
Publication Date: 2017-07-27 PubMed ID: 28750625PubMed Central: PMC5530493DOI: 10.1186/s12864-017-3943-8Google Scholar: Lookup
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Summary
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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 Publication
Researcher Affiliations
- Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
- Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
- Unité de Génétique Animale et Biologie Intégrative- UMR1313, INRA, Université Paris-Saclay, AgroParisTech, 78350, Jouy-en-Josas, France.
- The Robert H. Smith Faculty of Agriculture, Food and Environment, The Koret School of Veterinary Medicine, The Hebrew University, 76100, Rehovot, Israel.
- Institute of Animal Breeding and Genetics, Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Vienna, Austria.
- Department of Animal Science, University of Florida, Gainesville, FL, USA.
- Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Hannover, Germany.
- Lehrstuhl für Tierzucht der Technischen Universität München, Liesel-Beckmann-Strasse 1, 85354, Freising, Germany.
- School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
- Swiss Institute of Equine Medicine, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, and Agroscope, Länggassstrasse 124, 3001, Bern, Switzerland.
- School of Life and Environmental Sciences, Faculty of Veterinary Science, University of Sydney, Regimental Drive, B19-301 RMC Gunn, Sydney, NSW, 2006, Australia.
- Institute of Genetics, University of Bern, 3001, Bern, Switzerland.
- Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
- Institute of Genetics, University of Bern, 3001, Bern, Switzerland.
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Biotechnology Centre of Azores, University of Azores, Angra do heroísmo, Portugal.
- Unité de Génétique Animale et Biologie Intégrative- UMR1313, INRA, Université Paris-Saclay, AgroParisTech, 78350, Jouy-en-Josas, France.
- Biotechnology Centre of Azores, University of Azores, Angra do heroísmo, Portugal.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Champaign, IL, 61802, USA.
- Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Hannover, Germany.
- Veterinary Genetics Laboratory, University of California Davis, Davis, CA, USA.
- The Robert H. Smith Faculty of Agriculture, Food and Environment, The Koret School of Veterinary Medicine, The Hebrew University, 76100, Rehovot, Israel.
- Agroscope, Swiss National Stud Farm, 1580, Avenches, Switzerland.
- School of Life and Environmental Sciences, Faculty of Veterinary Science, University of Sydney, Regimental Drive, B19-301 RMC Gunn, Sydney, NSW, 2006, Australia.
- 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.
- Institute of Animal Breeding and Husbandry, Christian-Albrechts-University Kiel, Hermann-Rodewald-Strasse 6, 24098, Kiel, Germany.
- Department of Veterinary Medicine - Sport Horse Research Centre, University of Perugia, Perugia, Italy.
- School of Life and Environmental Sciences, Faculty of Veterinary Science, University of Sydney, Regimental Drive, B19-301 RMC Gunn, Sydney, NSW, 2006, Australia.
- Institute of Animal Breeding and Genetics, Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Vienna, Austria.
- 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.
- Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
- Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA. mccų@umn.edu.
MeSH Terms
- Animals
- Gene Frequency
- Genotyping Techniques / methods
- Genotyping Techniques / standards
- Horses / genetics
- Linkage Disequilibrium
- Oligonucleotide Array Sequence Analysis / methods
- Oligonucleotide Array Sequence Analysis / standards
- Polymorphism, Single Nucleotide
- Reference Standards
- Whole Genome Sequencing
Grant Funding
- K01 OD015134 / NIH HHS
- L40 TR001136 / NCATS NIH HHS
Conflict of Interest Statement
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.
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