Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds

Robert J. Schaefer; Mikkel Schubert; Ernest Bailey; Danika L. Bannasch; Eric Barrey; Gila Kahila Bar-Gal; Gottfried Brem; Samantha A. Brooks; Ottmar Distl; Ruedi Fries; Carrie J. Finno; Vinzenz Gerber; Bianca Haase; Vidhya Jagannathan; Ted Kalbfleisch; Tosso Leeb; Gabriella Lindgren; Maria Susana Lopes; Núria Mach; Artur da Câmara Machado; James N. MacLeod; Annette McCoy; Julia Metzger; Cecilia Penedo; Sagi Polani; Stefan Rieder; Imke Tammen; Jens Tetens; Georg Thaller; Andrea Verini-Supplizi; Claire M. Wade; Barbara Wallner; Ludovic Orlando; James R. Mickelson; Molly E. McCue

doi:10.1186/s12864-017-3943-8

Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds

Robert J. Schaefer, Mikkel Schubert, Ernest Bailey, Danika L. Bannasch, Eric Barrey, Gila Kahila Bar-Gal, Gottfried Brem, Samantha A. Brooks, Ottmar Distl, Ruedi Fries, Carrie J. Finno, Vinzenz Gerber, Bianca Haase, Vidhya Jagannathan, Ted Kalbfleisch, Tosso Leeb, Gabriella Lindgren, Maria Susana Lopes, Núria Mach, Artur da Câmara MachadoJames N. MacLeod, Annette McCoy, Julia Metzger, Cecilia Penedo, Sagi Polani, Stefan Rieder, Imke Tammen, Jens Tetens, Georg Thaller, Andrea Verini-Supplizi, Claire M. Wade, Barbara Wallner, Ludovic Orlando, James R. Mickelson, Molly E. McCue^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

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.

Original language	American English
Article number	565
Journal	BMC Genomics
Volume	18
Issue number	1
DOIs	https://doi.org/10.1186/s12864-017-3943-8
State	Published - 27 Jul 2017

Bibliographical note

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). Funding sources played no role in the design of this study or the collection, analysis, and the interpretation of data and in writing the manuscript.

Publisher Copyright:
© 2017 The Author(s).

Keywords

Equine genomics
Linkage disequilibrium
SNP chip
SNP discovery
SNP informativeness
SNP validation
SNP-tagging
Variant recalibration
Whole genome sequence

Access to Document

10.1186/s12864-017-3943-8

Cite this

Schaefer, R. J., Schubert, M., Bailey, E., Bannasch, D. L., Barrey, E., Bar-Gal, G. K., Brem, G., Brooks, S. A., Distl, O., Fries, R., Finno, C. J., Gerber, V., Haase, B., Jagannathan, V., Kalbfleisch, T., Leeb, T., Lindgren, G., Lopes, M. S., Mach, N., ... McCue, M. E. (2017). Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds. BMC Genomics, 18(1), Article 565. https://doi.org/10.1186/s12864-017-3943-8

@article{ab27d671432b4c2bb2d05d60df66e60c,

title = "Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds",

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.",

keywords = "Equine genomics, Linkage disequilibrium, SNP chip, SNP discovery, SNP informativeness, SNP validation, SNP-tagging, Variant recalibration, Whole genome sequence",

author = "Schaefer, {Robert J.} and Mikkel Schubert and Ernest Bailey and Bannasch, {Danika L.} and Eric Barrey and Bar-Gal, {Gila Kahila} and Gottfried Brem and Brooks, {Samantha A.} and Ottmar Distl and Ruedi Fries and Finno, {Carrie J.} and Vinzenz Gerber and Bianca Haase and Vidhya Jagannathan and Ted Kalbfleisch and Tosso Leeb and Gabriella Lindgren and Lopes, {Maria Susana} and N{\'u}ria Mach and {da C{\^a}mara Machado}, Artur and MacLeod, {James N.} and Annette McCoy and Julia Metzger and Cecilia Penedo and Sagi Polani and Stefan Rieder and Imke Tammen and Jens Tetens and Georg Thaller and Andrea Verini-Supplizi and Wade, {Claire M.} and Barbara Wallner and Ludovic Orlando and Mickelson, {James R.} and McCue, {Molly E.}",

note = "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{\textquoteright}Excellence Chaires d{\textquoteright}attractivit{\'e}, Universit{\'e} 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). Funding sources played no role in the design of this study or the collection, analysis, and the interpretation of data and in writing the manuscript. Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = jul,

day = "27",

doi = "10.1186/s12864-017-3943-8",

language = "American English",

volume = "18",

journal = "BMC Genomics",

issn = "1471-2164",

publisher = "BioMed Central Ltd.",

number = "1",

}

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, vol. 18, no. 1, 565. https://doi.org/10.1186/s12864-017-3943-8

TY - JOUR

T1 - Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds

AU - Schaefer, Robert J.

AU - Schubert, Mikkel

AU - Bailey, Ernest

AU - Bannasch, Danika L.

AU - Barrey, Eric

AU - Bar-Gal, Gila Kahila

AU - Brem, Gottfried

AU - Brooks, Samantha A.

AU - Distl, Ottmar

AU - Fries, Ruedi

AU - Finno, Carrie J.

AU - Gerber, Vinzenz

AU - Haase, Bianca

AU - Jagannathan, Vidhya

AU - Kalbfleisch, Ted

AU - Leeb, Tosso

AU - Lindgren, Gabriella

AU - Lopes, Maria Susana

AU - Mach, Núria

AU - da Câmara Machado, Artur

AU - MacLeod, James N.

AU - McCoy, Annette

AU - Metzger, Julia

AU - Penedo, Cecilia

AU - Polani, Sagi

AU - Rieder, Stefan

AU - Tammen, Imke

AU - Tetens, Jens

AU - Thaller, Georg

AU - Verini-Supplizi, Andrea

AU - Wade, Claire M.

AU - Wallner, Barbara

AU - Orlando, Ludovic

AU - Mickelson, James R.

AU - McCue, Molly E.

N1 - 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). Funding sources played no role in the design of this study or the collection, analysis, and the interpretation of data and in writing the manuscript. Publisher Copyright: © 2017 The Author(s).

PY - 2017/7/27

Y1 - 2017/7/27

N2 - 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.

AB - 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.

KW - Equine genomics

KW - Linkage disequilibrium

KW - SNP chip

KW - SNP discovery

KW - SNP informativeness

KW - SNP validation

KW - SNP-tagging

KW - Variant recalibration

KW - Whole genome sequence

UR - http://www.scopus.com/inward/record.url?scp=85026226414&partnerID=8YFLogxK

U2 - 10.1186/s12864-017-3943-8

DO - 10.1186/s12864-017-3943-8

M3 - Article

C2 - 28750625

AN - SCOPUS:85026226414

SN - 1471-2164

VL - 18

JO - BMC Genomics

JF - BMC Genomics

IS - 1

M1 - 565

ER -

Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this