Improving the resolution of canine genome-wide association studies using genotype imputation: A study of two breeds

Dog Biomedical Variant Database Consortium

Research output: Contribution to journalArticlepeer-review

Abstract

Genotype imputation using a reference panel that combines high-density array data and publicly available whole genome sequence consortium variant data is potentially a cost-effective method to increase the density of extant lower-density array datasets. In this study, three datasets (two Border Collie; one Italian Spinone) generated using a legacy array (Illumina CanineHD, 173 662 SNPs) were utilised to assess the feasibility and accuracy of this approach and to gather additional evidence for the efficacy of canine genotype imputation. The cosmopolitan reference panels used to impute genotypes comprised dogs of 158 breeds, mixed breed dogs, wolves and Chinese indigenous dogs, as well as breed-specific individuals genotyped using the Axiom Canine HD array. The two Border Collie reference panels comprised 808 individuals including 79 Border Collies and 426 326 or 426 332 SNPs; and the Italian Spinone reference panel comprised 807 individuals including 38 Italian Spinoni and 476 313 SNPs. A high accuracy for imputation was observed, with the lowest accuracy observed for one of the Border Collie datasets (mean R2 = 0.94) and the highest for the Italian Spinone dataset (mean R2 = 0.97). This study’s findings demonstrate that imputation of a legacy array study set using a reference panel comprising both breed-specific array data and multi-breed variant data derived from whole genomes is effective and accurate. The process of canine genotype imputation, using the valuable growing resource of publicly available canine genome variant datasets alongside breed-specific data, is described in detail to facilitate and encourage use of this technique in canine genetics.

Original languageEnglish (US)
Pages (from-to)703-713
Number of pages11
JournalAnimal Genetics
Volume52
Issue number5
DOIs
StatePublished - Oct 2021

Bibliographical note

Funding Information:
The Petplan Charitable Trust funded this study in the Border Collie (project number S18-688-726). Generation of datasets for the Italian Spinone were funded by the Italian Spinone Club of Great Britain. C.A.J., S.L.R., C.S.M. and E.C.S. are supported by the Kennel Club Charitable Trust. We thank the Oxford Genomics Centre at the Wellcome Centre for Human Genetics (funded by Wellcome Trust grant reference 203141/Z/16/Z) for the generation and initial processing of the Axiom array data. Illumina genotyping was conducted by GeneSeek (Neogen Genomics, Lincoln, NE, USA). We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC Hub grant G090074791070) for the whole genomes of 24 dogs. The sequencing of the whole genomes of four dogs was carried out by the University of Cambridge. The whole genomes of 157 other dogs were sequenced by Edinburgh Genomics Laboratories, University of Edinburgh. The whole genome sequencing of 82 of the dogs was part of the Give a Dog a Genome project. We also thank Natasha Olby for sharing whole genome data. We acknowledge all canine researchers who deposited dog whole genome sequencing data into public databases. We thank Dr Janine Lamb, University of Manchester, for critical review of the manuscript. We would like to thank all owners who provided samples from their dogs, whose data contributed to this study.

Funding Information:
The Petplan Charitable Trust funded this study in the Border Collie (project number S18‐688‐726). Generation of datasets for the Italian Spinone were funded by the Italian Spinone Club of Great Britain. C.A.J., S.L.R., C.S.M. and E.C.S. are supported by the Kennel Club Charitable Trust. We thank the Oxford Genomics Centre at the Wellcome Centre for Human Genetics (funded by Wellcome Trust grant reference 203141/Z/16/Z) for the generation and initial processing of the Axiom array data. Illumina genotyping was conducted by GeneSeek (Neogen Genomics, Lincoln, NE, USA). We thank the High‐Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC Hub grant G090074791070) for the whole genomes of 24 dogs. The sequencing of the whole genomes of four dogs was carried out by the University of Cambridge. The whole genomes of 157 other dogs were sequenced by Edinburgh Genomics Laboratories, University of Edinburgh. The whole genome sequencing of 82 of the dogs was part of the Give a Dog a Genome project. We also thank Natasha Olby for sharing whole genome data. We acknowledge all canine researchers who deposited dog whole genome sequencing data into public databases. We thank Dr Janine Lamb, University of Manchester, for critical review of the manuscript. We would like to thank all owners who provided samples from their dogs, whose data contributed to this study.

Publisher Copyright:
© 2021 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics

Keywords

  • Border Collie
  • Italian Spinone
  • genome-wide association study
  • imputation accuracy
  • whole genome sequencing

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