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Combining multi-OMICs information to identify key-regulator genes for pleiotropic effect on fertility and production traits in beef cattle.

ABSTRACT: The identification of biological processes related to the regulation of complex traits is a difficult task. Commonly, complex traits are regulated through a multitude of genes contributing each to a small part of the total genetic variance. Additionally, some loci can simultaneously regulate several complex traits, a phenomenon defined as pleiotropy. The lack of understanding on the biological processes responsible for the regulation of these traits results in the decrease of selection efficiency and the selection of undesirable hitchhiking effects. The identification of pleiotropic key-regulator genes can assist in developing important tools for investigating biological processes underlying complex traits. A multi-breed and multi-OMICs approach was applied to study the pleiotropic effects of key-regulator genes using three independent beef cattle populations evaluated for fertility traits. A pleiotropic map for 32 traits related to growth, feed efficiency, carcass and meat quality, and reproduction was used to identify genes shared among the different populations and breeds in pleiotropic regions. Furthermore, data-mining analyses were performed using the Cattle QTL database (CattleQTLdb) to identify the QTL category annotated in the regions around the genes shared among breeds. This approach allowed the identification of a main gene network (composed of 38 genes) shared among breeds. This gene network was significantly associated with thyroid activity, among other biological processes, and displayed a high regulatory potential. In addition, it was possible to identify genes with pleiotropic effects related to crucial biological processes that regulate economically relevant traits associated with fertility, production and health, such as MYC, PPARG, GSK3B, TG and IYD genes. These genes will be further investigated to better understand the biological processes involved in the expression of complex traits and assist in the identification of functional variants associated with undesirable phenotypes, such as decreased fertility, poor feed efficiency and negative energetic balance.

SUBMITTER: Fonseca PAS

PROVIDER: S-EPMC6193631 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Combining multi-OMICs information to identify key-regulator genes for pleiotropic effect on fertility and production traits in beef cattle.

Fonseca Pablo Augusto de Souza PAS Id-Lahoucine Samir S Reverter Antonio A Medrano Juan F JF Fortes Marina S MS Casellas Joaquim J Miglior Filippo F Brito Luiz L Carvalho Maria Raquel S MRS Schenkel Flávio S FS Nguyen Loan T LT Porto-Neto Laercio R LR Thomas Milton G MG Cánovas Angela A

PloS one 20181018 10

The identification of biological processes related to the regulation of complex traits is a difficult task. Commonly, complex traits are regulated through a multitude of genes contributing each to a small part of the total genetic variance. Additionally, some loci can simultaneously regulate several complex traits, a phenomenon defined as pleiotropy. The lack of understanding on the biological processes responsible for the regulation of these traits results in the decrease of selection efficienc ...[more]

PMID: 30335783

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Project description:Carcass and meat quality are two important attributes for the beef industry because they drive profitability and consumer demand. These traits are of even greater importance in crossbred cattle used in subtropical and tropical regions for their superior adaptability because they tend to underperform compared to their purebred counterparts. Many of these traits are challenging and expensive to measure and unavailable until late in life or after the animal is harvested, hence unrealistic to improve through traditional phenotypic selection, but perfect candidates for genomic selection. Before genomic selection can be implemented in crossbred populations, it is important to explore if pleiotropic effects exist between carcass and meat quality traits. Therefore, the objective of this study was to identify genomic regions with pleiotropic effects on carcass and meat quality traits in a multibreed Angus-Brahman population that included purebred and crossbred animals. Data included phenotypes for 10 carcass and meat quality traits from 2,384 steers, of which 1,038 were genotyped with the GGP Bovine F-250. Single-trait genome-wide association studies were first used to investigate the relevance of direct additive genetic effects on each carcass, sensory and visual meat quality traits. A second analysis for each trait included all other phenotypes as covariates to correct for direct causal effects from identified genomic regions with pure direct effects on the trait under analysis. Five genomic windows on chromosomes BTA5, BTA7, BTA18, and BTA29 explained more than 1% of additive genetic variance of two or more traits. Moreover, three suggestive pleiotropic regions were identified on BTA10 and BTA19. The 317 genes uncovered in pleiotropic regions included anchoring and cytoskeletal proteins, key players in cell growth, muscle development, lipid metabolism and fat deposition, and important factors in muscle proteolysis. A functional analysis of these genes revealed GO terms directly related to carcass quality, meat quality, and tenderness in beef cattle, including calcium-related processes, cell signaling, and modulation of cell-cell adhesion. These results contribute with novel information about the complex genetic architecture and pleiotropic effects of carcass and meat quality traits in crossbred beef cattle.

Project description:BACKGROUND:In livestock, deleterious recessive alleles can result in reduced economic performance of homozygous individuals in multiple ways, e.g. early embryonic death, death soon after birth, or semi-lethality with incomplete penetrance causing reduced viability. While death is an easy phenotype to score, reduced viability is not as easy to identify. However, it can sometimes be observed as reduced conception rates, longer calving intervals, or lower survival for live born animals. METHODS:In this paper, we searched for haplotypes that carry putatively recessive lethal or semi-lethal alleles in 132,725 genotyped Irish beef cattle from five breeds: Aberdeen Angus, Charolais, Hereford, Limousin, and Simmental. We phased the genotypes in sliding windows along the genome and used five tests to identify haplotypes with absence of or reduced homozygosity. Then, we associated the identified haplotypes with 44,351 insemination records that indicated early embryonic death, and postnatal survival records. Finally, we assessed haplotype pleiotropy by estimating substitution effects on estimates of breeding value for 15 economically important traits in beef production. RESULTS:We found support for one haplotype that carries a putatively recessive lethal (chromosome 16 in Simmental) and two haplotypes that carry semi-lethal alleles (chromosome 14 in Aberdeen Angus and chromosome 19 in Charolais), with population frequencies of 8.8, 15.2, and 14.4%, respectively. These three haplotypes showed pleiotropic effects on economically important traits for beef production. Their allele substitution effects are €2.30, €3.42, and €1.47 for the terminal index and €1.03, -?€3.11, and -?€0.88 for the replacement index, where the standard deviations for the terminal index are €22.52, €18.65, and €22.70 and for the replacement index they are €31.35, €29.82, and €35.79. We identified ZFAT as the candidate gene for semi-lethality in Aberdeen Angus, several candidate genes for the lethal Simmental haplotype, and no candidate genes for the semi-lethal Charolais haplotype. CONCLUSIONS:We analysed genotype, reproduction, survival, and production data to detect haplotypes that carry putatively recessive lethal or semi-lethal alleles in Irish beef cattle and identified one lethal and two semi-lethal haplotypes, which have pleiotropic effects on economically important traits in beef production.

Dataset Information

Combining multi-OMICs information to identify key-regulator genes for pleiotropic effect on fertility and production traits in beef cattle.

Publications

Combining multi-OMICs information to identify key-regulator genes for pleiotropic effect on fertility and production traits in beef cattle.

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