Article (Scientific journals)
High-resolution structural variants catalogue in a large-scale whole genome sequenced bovine family cohort data.
Lee, Young Lim; Bosse, Mirte; Takeda, Haruko et al.
2023In BMC Genomics, 24 (1), p. 225
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Keywords :
Cattle; Copy number variants; Linkage disequilibrium; Structural variants; Whole genome sequencing; eQTL; POPDC3 protein, human; Muscle Proteins; Cell Adhesion Molecules; Female; Humans; Animals; Genotype; DNA Copy Number Variations; Haplotypes; Polymorphism, Single Nucleotide; Muscle Proteins/genetics; Cell Adhesion Molecules/genetics; Genome; Genomics/methods; Genetics; Biotechnology
Abstract :
[en] [en] BACKGROUND: Structural variants (SVs) are chromosomal segments that differ between genomes, such as deletions, duplications, insertions, inversions and translocations. The genomics revolution enabled the discovery of sub-microscopic SVs via array and whole-genome sequencing (WGS) data, paving the way to unravel the functional impact of SVs. Recent human expression QTL mapping studies demonstrated that SVs play a disproportionally large role in altering gene expression, underlining the importance of including SVs in genetic analyses. Therefore, this study aimed to generate and explore a high-quality bovine SV catalogue exploiting a unique cattle family cohort data (total 266 samples, forming 127 trios). RESULTS: We curated 13,731 SVs segregating in the population, consisting of 12,201 deletions, 1,509 duplications, and 21 multi-allelic CNVs (> 50-bp). Of these, we validated a subset of copy number variants (CNVs) utilising a direct genotyping approach in an independent cohort, indicating that at least 62% of the CNVs are true variants, segregating in the population. Among gene-disrupting SVs, we prioritised two likely high impact duplications, encompassing ORM1 and POPDC3 genes, respectively. Liver expression QTL mapping results revealed that these duplications are likely causing altered gene expression, confirming the functional importance of SVs. Although most of the accurately genotyped CNVs are tagged by single nucleotide polymorphisms (SNPs) ascertained in WGS data, most CNVs were not captured by individual SNPs obtained from a 50K genotyping array. CONCLUSION: We generated a high-quality SV catalogue exploiting unique whole genome sequenced bovine family cohort data. Two high impact duplications upregulating the ORM1 and POPDC3 are putative candidates for postpartum feed intake and hoof health traits, thus warranting further investigation. Generally, CNVs were in low LD with SNPs on the 50K array. Hence, it remains crucial to incorporate CNVs via means other than tagging SNPs, such as investigation of tagging haplotypes, direct imputation of CNVs, or direct genotyping as done in the current study. The SV catalogue and the custom genotyping array generated in the current study will serve as valuable resources accelerating utilisation of full spectrum of genetic variants in bovine genomes.
Disciplines :
Genetics & genetic processes
Author, co-author :
Lee, Young Lim ;  Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA)
Bosse, Mirte;  Animal Breeding and Genomics, Wageningen University & Research, Wageningen, the Netherlands
Takeda, Haruko ;  Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA) > Génomique animale
Moreira, Gabriel Costa Monteiro;  Unit of Animal Genomics, Faculty of Veterinary Medicine, GIGA-R &, University of Liège, Liège, Belgium
Karim, Latifa ;  Université de Liège - ULiège > GIGA > GIGA Platform Genomics
Druet, Tom ;  Université de Liège - ULiège > Département des sciences de la vie
Oget-Ebrad, Claire;  Unit of Animal Genomics, Faculty of Veterinary Medicine, GIGA-R &, University of Liège, Liège, Belgium
Coppieters, Wouter ;  Université de Liège - ULiège > GIGA > GIGA Platform Genomics
Veerkamp, Roel F;  Animal Breeding and Genomics, Wageningen University & Research, Wageningen, the Netherlands
Groenen, Martien A M;  Animal Breeding and Genomics, Wageningen University & Research, Wageningen, the Netherlands
Georges, Michel  ;  Université de Liège - ULiège > GIGA > GIGA Innovation
Bouwman, Aniek C;  Animal Breeding and Genomics, Wageningen University & Research, Wageningen, the Netherlands
Charlier, Carole  ;  Université de Liège - ULiège > GIGA > GIGA Medical Genomics
More authors (3 more) Less
Language :
English
Title :
High-resolution structural variants catalogue in a large-scale whole genome sequenced bovine family cohort data.
Publication date :
01 May 2023
Journal title :
BMC Genomics
eISSN :
1471-2164
Publisher :
Springer Science and Business Media LLC, England
Volume :
24
Issue :
1
Pages :
225
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Seventh Framework Programme
H2020
Funders :
EZK - Ministerie van Economische Zaken en Klimaat [NL]
ERC - European Research Council [BE]
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