Developing a 670k Genotyping Array to Tag ~2M SNPs Across 24 Horse Breeds

Authors

Robert J. Schaefer, University of Minnesota - Twin Cities
Mikkel Schubert, University of Copenhagen, Denmark
Ernest F. Bailey, University of KentuckyFollow
Danika L. Bannasch, University of California - Davis
Eric Barrey, University of Paris - Saclay, France
Gila Kahila Bar-Gal, The Hebrew University, Israel
Gottfried Brem, University of Veterinary Medicine Vienna, Austria
Samantha A. Brooks, University of Florida
Ottmar Distl, University of Veterinary Medicine, Germany
Ruedi Fries, University of Munich, Germany
Carrie J. Finno, University of California - Davis
Vinzenz Gerber, University of Bern, Switzerland
Bianca Haase, University of Sydney, Australia
Vidhya Jagannathan, University of Bern, Switzerland
Ted Kalbfleisch, University of Louisville
Tosso Leeb, University of Bern, Switzerland
Gabriella Lindgren, Swedish University of Agricultural Sciences, Sweden
Maria Susana Lopes, University of Azores, Portugal
Núria Mach, Université Paris - Saclay, France
Artur da Câmara Machado, University of Azores, Portugal
James N. Macleod, University of KentuckyFollow
Annette McCoy, University of Illinois at Urbana-Champaign
Julia Metzger, University of Veterinary Medicine, Germany
Cecilia Penedo, University of California - Davis
Sagi Polani, The Hebrew University, Israel
Stefan Rieder, Agroscope, Switzerland
Imke Tammen, University of Sydney, Australia
Jens Tetens, University of Kiell, Germany
Georg Thaller, University of Kiell, Germany
Andrea Verini-Supplizi, University of Perugia, Italy

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

Document Type

Article

Publication Date

7-27-2017

Notes/Citation Information

Published in BMC Genomics, v. 18, 565, p. 1-18.

© The Author(s). 2017

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Due to the large number of authors, only the first 30 and the authors affiliated with the University of Kentucky are listed in the author section above. For the complete list of authors, please download this article.

Digital Object Identifier (DOI)

https://doi.org/10.1186/s12864-017-3943-8

Funding Information

Support for the generation of whole genome sequence came from the following sources:

• USDA NIFA project 2012-67,015-19,432 and Minnesota Agricultural Experiment Station Multistate project MIN-62-090.
• The National Animal Genome Project (NRSP8) through the equine genome coordinator: USDA-NRSP8 (2013-2018) horse-technical-committee coordinator funds.
• The Danish Council for Independent Research, Natural Sciences (Grant 4002-00152B); the Danish National Research Foundation (Grant DNRF94); Initiative d’Excellence Chaires d’attractivité, Université de Toulouse (OURASI), and; the European Research Council (ERC-CoG-2015-681,605).
• The Bavarian Ministry State Ministry for Food and Agriculture, and Forestry (A/13/39).
• The Laboratory of Molecular Evolution, The Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Israel) for contributing pure-bred Arabian whole-genomes on behalf of The Israel Science Foundation (ISF) grant #1365/10.
• The Swedish Research Council Formas (221-2013-1661) and the Swedish Research Council VR (621-2012-4666).

Related Content

Whole genome sequences are available in the following NCBI BioProjects: PRJEB14779, PRJNA273402, and PRJEB10098. Additional sequences have are restricted in availability due to pre-existing material transfer agreements and can be requested by contacting the contributing investigator in Additional file 1: Table S1. Genotypes for horses on the MNec2M array will be released upon publication. Genome positions for all 23 million discovered SNPs have been submitted to dbSNP as well as the European Variation Archive.

Repository Citation

Schaefer, Robert J.; Schubert, Mikkel; Bailey, Ernest F.; Bannasch, Danika L.; Barrey, Eric; Bar-Gal, Gila Kahila; Brem, Gottfried; Brooks, Samantha A.; Distl, Ottmar; Fries, Ruedi; Finno, Carrie J.; Gerber, Vinzenz; Haase, Bianca; Jagannathan, Vidhya; Kalbfleisch, Ted; Leeb, Tosso; Lindgren, Gabriella; Lopes, Maria Susana; Mach, Núria; da Câmara Machado, Artur; Macleod, James N.; McCoy, Annette; Metzger, Julia; Penedo, Cecilia; Polani, Sagi; Rieder, Stefan; Tammen, Imke; Tetens, Jens; Thaller, Georg; and Verini-Supplizi, Andrea, "Developing a 670k Genotyping Array to Tag ~2M SNPs Across 24 Horse Breeds" (2017). Maxwell H. Gluck Equine Research Center Faculty Publications. 14.
https://uknowledge.uky.edu/gerc_facpub/14