Evidence for and Localization of Proposed Causative Variants in Cattle and Pig Genomes

Overview

Journal Genet Sel Evol

Publisher Biomed Central

Specialties Biology
Genetics

Date 2021 Aug 31

PMID 34461824

Citations 13

Authors

Martin Johnsson

Melissa K Jungnickel

Affiliations

Soon will be listed here.

Abstract

Background: This paper reviews the localization of published potential causative variants in contemporary pig and cattle reference genomes, and the evidence for their causality. In spite of the difficulties inherent to the identification of causative variants from genetic mapping and genome-wide association studies, researchers in animal genetics have proposed putative causative variants for several traits relevant to livestock breeding.

Results: For this review, we read the literature that supports potential causative variants in 13 genes (ABCG2, DGAT1, GHR, IGF2, MC4R, MSTN, NR6A1, PHGK1, PRKAG3, PLRL, RYR1, SYNGR2 and VRTN) in cattle and pigs, and localized them in contemporary reference genomes. We review the evidence for their causality, by aiming to separate the evidence for the locus, the proposed causative gene and the proposed causative variant, and report the bioinformatic searches and tactics needed to localize the sequence variants in the cattle or pig genome.

Conclusions: Taken together, there is usually good evidence for the association at the locus level, some evidence for a specific causative gene at eight of the loci, and some experimental evidence for a specific causative variant at six of the loci. We recommend that researchers who report new potential causative variants use referenced coordinate systems, show local sequence context, and submit variants to repositories.

Citing Articles

Sequence-based GWAS in 180,000 German Holstein cattle reveals new candidate variants for milk production traits.

Krizanac A, Reimer C, Heise J, Liu Z, Pryce J, Bennewitz J Genet Sel Evol. 2025; 57(1):3.

PMID: 39905301 PMC: 11796172. DOI: 10.1186/s12711-025-00951-9.

Bioinformatic approach to identifying causative missense polymorphisms in animal genomes.

Peka M, Balatsky V BMC Genomics. 2024; 25(1):1226.

PMID: 39701989 PMC: 11660588. DOI: 10.1186/s12864-024-11126-z.

Single nucleotide polymorphism profile for quantitative trait nucleotide in populations with small effective size and its impact on mapping and genomic predictions.

Pocrnic I, Lourenco D, Misztal I Genetics. 2024; 227(4).

PMID: 38913695 PMC: 11304960. DOI: 10.1093/genetics/iyae103.

A DIO2 missense mutation and its impact on fetal response to PRRSV infection.

Ko H, Pasternak J, Mulligan M, Hamonic G, Ramesh N, MacPhee D BMC Vet Res. 2024; 20(1):255.

PMID: 38867209 PMC: 11167750. DOI: 10.1186/s12917-024-04099-4.

Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle.

Tang Y, Zhang J, Li W, Liu X, Chen S, Mi S BMC Genomics. 2024; 25(1):445.

PMID: 38711039 PMC: 11075310. DOI: 10.1186/s12864-024-10346-7.

References

Velez-Irizarry D, Casiro S, Daza K, Bates R, Raney N, Steibel J . Genetic control of longissimus dorsi muscle gene expression variation and joint analysis with phenotypic quantitative trait loci in pigs. BMC Genomics. 2019; 20(1):3. PMC: 6319002. DOI: 10.1186/s12864-018-5386-2. View

de Koning D, Harlizius B, Rattink A, Groenen M, Brascamp E, van Arendonk J . Detection and characterization of quantitative trait loci for meat quality traits in pigs. J Anim Sci. 2002; 79(11):2812-9. DOI: 10.2527/2001.79112812x. View

Raven L, Cocks B, Hayes B . Multibreed genome wide association can improve precision of mapping causative variants underlying milk production in dairy cattle. BMC Genomics. 2014; 15:62. PMC: 3905911. DOI: 10.1186/1471-2164-15-62. View

Otero J, Miguel V, Gonzalez-Lobato L, Garcia-Villalba R, Espin J, Prieto J . Effect of bovine ABCG2 polymorphism Y581S SNP on secretion into milk of enterolactone, riboflavin and uric acid. Animal. 2015; 10(2):238-47. DOI: 10.1017/S1751731115002141. View

McPherron A, Lawler A, Lee S . Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997; 387(6628):83-90. DOI: 10.1038/387083a0. View

Grobet L, Martin L, Poncelet D, Pirottin D, Brouwers B, Riquet J . A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genet. 1997; 17(1):71-4. DOI: 10.1038/ng0997-71. View

Renaville R, Hammadi M, Portetelle D . Role of the somatotropic axis in the mammalian metabolism. Domest Anim Endocrinol. 2002; 23(1-2):351-60. DOI: 10.1016/s0739-7240(02)00170-4. View

Duan Y, Zhang H, Zhang Z, Gao J, Yang J, Wu Z . VRTN is Required for the Development of Thoracic Vertebrae in Mammals. Int J Biol Sci. 2018; 14(6):667-681. PMC: 6001657. DOI: 10.7150/ijbs.23815. View

Verardo L, Sevon-Aimonen M, Serenius T, Hietakangas V, Uimari P . Whole-genome association analysis of pork meat pH revealed three significant regions and several potential genes in Finnish Yorkshire pigs. BMC Genet. 2017; 18(1):13. PMC: 5307873. DOI: 10.1186/s12863-017-0482-x. View

10.

Flori L, Fritz S, Jaffrezic F, Boussaha M, Gut I, Heath S . The genome response to artificial selection: a case study in dairy cattle. PLoS One. 2009; 4(8):e6595. PMC: 2722727. DOI: 10.1371/journal.pone.0006595. View

11.

Littlejohn M, Henty K, Tiplady K, Johnson T, Harland C, Lopdell T . Functionally reciprocal mutations of the prolactin signalling pathway define hairy and slick cattle. Nat Commun. 2014; 5:5861. PMC: 4284646. DOI: 10.1038/ncomms6861. View

12.

Lenffer J, Nicholas F, Castle K, Rao A, Gregory S, Poidinger M . OMIA (Online Mendelian Inheritance in Animals): an enhanced platform and integration into the Entrez search interface at NCBI. Nucleic Acids Res. 2005; 34(Database issue):D599-601. PMC: 1347514. DOI: 10.1093/nar/gkj152. View

13.

Randhawa I, Khatkar M, Thomson P, Raadsma H . A Meta-Assembly of Selection Signatures in Cattle. PLoS One. 2016; 11(4):e0153013. PMC: 4821596. DOI: 10.1371/journal.pone.0153013. View

14.

Nezer C, Moreau L, Brouwers B, Coppieters W, Detilleux J, Hanset R . An imprinted QTL with major effect on muscle mass and fat deposition maps to the IGF2 locus in pigs. Nat Genet. 1999; 21(2):155-6. DOI: 10.1038/5935. View

15.

Wang K, Tang X, Xie Z, Zou X, Li M, Yuan H . CRISPR/Cas9-mediated knockout of myostatin in Chinese indigenous Erhualian pigs. Transgenic Res. 2017; 26(6):799-805. DOI: 10.1007/s11248-017-0044-z. View

16.

Lopdell T, Tiplady K, Struchalin M, Johnson T, Keehan M, Sherlock R . DNA and RNA-sequence based GWAS highlights membrane-transport genes as key modulators of milk lactose content. BMC Genomics. 2017; 18(1):968. PMC: 5731188. DOI: 10.1186/s12864-017-4320-3. View

17.

Xiang R, van den Berg I, MacLeod I, Hayes B, Prowse-Wilkins C, Wang M . Quantifying the contribution of sequence variants with regulatory and evolutionary significance to 34 bovine complex traits. Proc Natl Acad Sci U S A. 2019; 116(39):19398-19408. PMC: 6765237. DOI: 10.1073/pnas.1904159116. View

18.

Chavez A, Scheiman J, Vora S, Pruitt B, Tuttle M, Iyer E . Highly efficient Cas9-mediated transcriptional programming. Nat Methods. 2015; 12(4):326-8. PMC: 4393883. DOI: 10.1038/nmeth.3312. View

19.

Tait-Burkard C, Doeschl-Wilson A, McGrew M, Archibald A, Sang H, Houston R . Livestock 2.0 - genome editing for fitter, healthier, and more productive farmed animals. Genome Biol. 2018; 19(1):204. PMC: 6258497. DOI: 10.1186/s13059-018-1583-1. View

20.

Foissac S, Djebali S, Munyard K, Vialaneix N, Rau A, Muret K . Multi-species annotation of transcriptome and chromatin structure in domesticated animals. BMC Biol. 2019; 17(1):108. PMC: 6936065. DOI: 10.1186/s12915-019-0726-5. View