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

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

doi:10.1101/112979

Cited by 11 publications

(14 citation statements)

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“…A recent study designed two chips for genotype imputation: MNEc670k, consisting of ~670k SNPs, and MNEc2M, a next‐generation HD SNP chip (~2 million SNPs). Genotype imputation accuracy from the MNEc670k SNP set to the MNEc2M SNP set ranged between 96.6% and 99.4% in the fifteen breeds tested (Schaefer et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…After these two medium‐density (MD) chips, a high‐density (HD) commercial chip, the Affymetrix Axiom Equine genotyping array (670k), was developed by the selection of 670,806 SNPs amongst the 2 million SNPs of an experimental chip designed from multiple breeds by the international consortium. This chip consisted of 626,710 new SNP markers and 44,096 SNPs already present on both MD chips (Schaefer et al., ). Currently, the Affymetrix Axiom Equine genotyping array and the Illumina Equine SNP70 BeadChip are the two commercial chips available.…”

Section: Introductionmentioning

confidence: 99%

“…And recently, Schaefer et al. () assessed imputation accuracy from the HD chip (670k) to a set of 2 million SNPs selected by them. However, none of the studies investigated the accuracy of the genotype imputation from medium‐ to high‐density chip genotypes.…”

Section: Introductionmentioning

confidence: 99%

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Genotype imputation accuracy in multiple equine breeds from medium‐ to high‐density genotypes

Chassier

Barrey

Robert

et al. 2018

J Animal Breeding Genetics

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Genotype imputation is now a key component of genomic analyses as it increases the density of available genotypes within a population. However, many factors can influence imputation accuracy. The aim of this study was to assess and compare the accuracy of imputation of high‐density genotypes (Affymetrix Axiom Equine genotyping array, 670,806 SNPs) from two moderate‐density genotypes (Illumina Equine SNP50 BeadChip, 54,602 SNPs and Illumina Equine SNP70 BeadChip, 65,157 SNPs), using single‐breed or multiple‐breed reference sets. Genotypes were available from five groups of horse breeds: Arab (AR, 1,207 horses), Trotteur Français (TF, 979 horses), Selle Français (SF, 1,979 horses), Anglo‐Arab (AA, 229 horses) and various foreign sport horses (FH, 209 horses). The proportions of horses genotyped with the high‐density (HD) chip in each breed group were 10% in AA, 15% in AR and FH, 30% in TF and 57% in SF. A validation set consisting of one‐third of the horses genotyped with the HD chip was formed and their genotypes deleted. Two imputation strategies were compared, one in which the reference population consisted only of horses from the same breed group as in the validation set, and another with horses from all breed groups. For the first strategy, concordance rates (CRs) ranged from 97.8% (AR) to 99.0% (TF) and correlations (r²) from 0.94 (AR) to 0.99 (TF). For the second strategy, CR ranged from 97.4% (AR) to 98.9% (TF) and r² from 0.93 (AR) to 0.99 (TF). Overall, the results show a small advantage of within‐breed imputation compared with multi‐breed imputation. Adding horses from different breed groups to the reference population does not improve the accuracy of imputation. Imputation provides an accurate means of combining data sets from different genotyping platforms, now necessary with the increasing use of the recently developed Affymetrix Axiom Equine genotyping array.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genotype imputation accuracy in multiple equine breeds from medium‐ to high‐density genotypes

Chassier

Barrey

Robert

et al. 2018

J Animal Breeding Genetics

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“…The 55 EPL samples genotyped on the Axiom™ Equine 670K SNP Genotyping Array [71] included 24 male and 51 female EPL conceptuses from Thoroughbred, Warmblood, and unknown breed pregnancies, with a spread of mare ages and gestational ages. Mare ages ranged from 3 to 21 years old.…”

Section: Methodsmentioning

confidence: 99%

Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse

Shilton

Kahler

Davis

et al. 2020

Preprint

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Chromosome abnormalities are well documented in human spontaneous abortion studies, yet rarely reported in domesticated animals. Rodent models have previously been used to study the effects of maternal ageing on oocyte quality and ultimately aneuploidy, however the differing endocrine profiles, oocyte characteristics and the polytocous nature of rodents are limitations for translation into human medicine. Early Pregnancy Loss (EPL) occurs in 5-10% of confirmed equine pregnancies and has no diagnosis in over 80% of cases. Aneuploidy has never been described in equine pregnancy loss, thus the objectives of this study were to quantify the frequency and characteristics of aneuploidy associated with equine EPL. EPL conceptuses were submitted from clinical cases of spontaneous pregnancy loss (14-65 days of gestation) between 2013 and 2018. Age matched control conceptuses were obtained from terminated clinically normal pregnancies (CNP). Aneuploidy was detected in 12/55 EPLs (21.8%), 0/10 CNP, 0/5 healthy term chorioallantois, and 0/5 healthy adult mares via genotyping. Whole genome sequencing (30X) and ddPCR validated results. Aneuploidies involved 10/32 equine chromosomes, consisting of nine trisomies and three monosomies. Autosomal aneuploidies were detected in both placental and fetal compartments in all samples tested. Aneuploid types (7/9) were mostly unique to EPL, supporting their embryonic/fetal lethality. Presenting the first evidence of aneuploidies in failed equine pregnancies not only provides the initial step in identifying genetic causes for these early losses, but also offers the horse as a new model for studying naturally occurring aneuploidy. We also demonstrate that SNP arrays provide a simple, cost effective way to screen aneuploidies across a large population.Author SummaryThe first 8 weeks of pregnancy is a critical time in both humans and horses, as the majority of pregnancy losses occur during this period. Despite such high prevalence, many cases do not have a known cause. Abnormal chromosome number (aneuploidy) is the most common finding in human pregnancy loss studies, but to date no equivalent study has been performed in domesticated animals, including the horse. We studied the genetics of naturally occurring pregnancy losses from Thoroughbred horses and found a similar level of aneuploidy to that observed in women. As humans and horses share similarities in their reproductive biology (ageing eggs, increased pregnancy loss in older mothers, similar key hormones), we suggest that by comparing the genetics of these two species, greater advances in identifying causes of aneuploidy pregnancy can be reached. Thoroughbred horses also tend to be more inbred than humans, facilitating the identification of mutations that increase the chance of aneuploidy, and this knowledge could potentially be applied in human medicine, as well as in species conservation.

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“…This assembly was generated using the best genomic sequencing and assembly technologies available at the time, namely: Sanger sequencing, bacterial artificial chromosome (BAC) end pairs, radiation hybrid (RH) mapping, and fluorescence in situ hybridization (FISH) mapping. Since then, many researchers have used this reference genome to study the genetics of various traits in horses [3][4][5][6][7][8][9] , as well as their health [10][11][12][13] and evolution [14][15][16][17] . However, EquCab2 contains numerous gaps in scaffolds as well as sequences unassigned to chromosomes, and genomic DNA resequencing 18 and gene annotation 19 studies have found inconsistencies in this genome.…”

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confidence: 99%

EquCab3, an Updated Reference Genome for the Domestic Horse

Kalbfleisch¹,

Rice²,

DePriest³

et al. 2018

Preprint

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EquCab2, a high-quality reference genome for the domestic horse, was released in 2007.Since then, it has served as the foundation for nearly all genomic work done in equids. Recent advances in genomic sequencing technology and computational assembly methods have allowed scientists to improve reference assemblies of large animal and plant genomes in terms of contiguity and composition. In 2014, the equine genomics research community began a project to improve the reference sequence for the horse, building upon the solid foundation of EquCab2 and incorporating new short-read data, long-read data, and proximity ligation data. The result, EquCab3, is presented here. The count of non-N bases in the incorporated chromosomes is improved from 2.33Gb in EquCab2 to 2.41Gb from EquCab3. Contiguity has also been improved nearly 40-fold with a contig N50 of 4.5Mb and scaffold contiguity enhanced to where all but one of the 32 chromosomes is comprised of a single scaffold.

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

Abstract: Background

Cited by 11 publications

References 46 publications

Genotype imputation accuracy in multiple equine breeds from medium‐ to high‐density genotypes

Genotype imputation accuracy in multiple equine breeds from medium‐ to high‐density genotypes

Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse

EquCab3, an Updated Reference Genome for the Domestic Horse

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