Meta-Analysis of Heifer Traits Identified Reproductive Pathways in <i>Bos indicus</i> Cattle
Fertility traits measured early in life define the reproductive potential of heifers. Knowledge of genetics and biology can help devise genomic selection methods to improve heifer fertility. In this study, we used ~2400 Brahman cattle to perform GWAS and multi-trait meta-analysis to determine genomi...
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2021-05-01
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Muhammad S. Tahir Laercio R. Porto-Neto Cedric Gondro Olasege B. Shittu Kimberley Wockner Andre W. L. Tan Hugo R. Smith Gabriela C. Gouveia Jagish Kour Marina R. S. Fortes |
spellingShingle |
Muhammad S. Tahir Laercio R. Porto-Neto Cedric Gondro Olasege B. Shittu Kimberley Wockner Andre W. L. Tan Hugo R. Smith Gabriela C. Gouveia Jagish Kour Marina R. S. Fortes Meta-Analysis of Heifer Traits Identified Reproductive Pathways in <i>Bos indicus</i> Cattle Genes GWAS meta-analysis gene ontology <i>Bos indicus</i> Brahman cattle fertility |
author_facet |
Muhammad S. Tahir Laercio R. Porto-Neto Cedric Gondro Olasege B. Shittu Kimberley Wockner Andre W. L. Tan Hugo R. Smith Gabriela C. Gouveia Jagish Kour Marina R. S. Fortes |
author_sort |
Muhammad S. Tahir |
title |
Meta-Analysis of Heifer Traits Identified Reproductive Pathways in <i>Bos indicus</i> Cattle |
title_short |
Meta-Analysis of Heifer Traits Identified Reproductive Pathways in <i>Bos indicus</i> Cattle |
title_full |
Meta-Analysis of Heifer Traits Identified Reproductive Pathways in <i>Bos indicus</i> Cattle |
title_fullStr |
Meta-Analysis of Heifer Traits Identified Reproductive Pathways in <i>Bos indicus</i> Cattle |
title_full_unstemmed |
Meta-Analysis of Heifer Traits Identified Reproductive Pathways in <i>Bos indicus</i> Cattle |
title_sort |
meta-analysis of heifer traits identified reproductive pathways in <i>bos indicus</i> cattle |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2021-05-01 |
description |
Fertility traits measured early in life define the reproductive potential of heifers. Knowledge of genetics and biology can help devise genomic selection methods to improve heifer fertility. In this study, we used ~2400 Brahman cattle to perform GWAS and multi-trait meta-analysis to determine genomic regions associated with heifer fertility. Heifer traits measured were pregnancy at first mating opportunity (PREG1, a binary trait), first conception score (FCS, score 1 to 3) and rebreeding score (REB, score 1 to 3.5). The heritability estimates were 0.17 (0.03) for PREG1, 0.11 (0.05) for FCS and 0.28 (0.05) for REB. The three traits were highly genetically correlated (0.75–0.83) as expected. Meta-analysis was performed using SNP effects estimated for each of the three traits, adjusted for standard error. We identified 1359 significant SNPs (<i>p</i>-value < 9.9 × 10<sup>−6</sup> at FDR < 0.0001) in the multi-trait meta-analysis. Genomic regions of 0.5 Mb around each significant SNP from the meta-analysis were annotated to create a list of 2560 positional candidate genes. The most significant SNP was in the vicinity of a genomic region on chromosome 8, encompassing the genes <i>SLC44A1</i>, <i>FSD1L</i>, <i>FKTN</i>, <i>TAL2</i> and <i>TMEM38B</i>. The genomic region in humans that contains homologs of these genes is associated with age at puberty in girls. Top significant SNPs pointed to additional fertility-related genes, again within a 0.5 Mb region, including <i>ESR2</i>, <i>ITPR1</i>, <i>GNG2, RGS9BP, ANKRD27</i>, <i>TDRD12</i>, <i>GRM1, MTHFD1, PTGDR</i> and <i>NTNG1.</i> Functional pathway enrichment analysis resulted in many positional candidate genes relating to known fertility pathways, including GnRH signaling, estrogen signaling, progesterone mediated oocyte maturation, cAMP signaling, calcium signaling, glutamatergic signaling, focal adhesion, PI3K-AKT signaling and ovarian steroidogenesis pathway. The comparison of results from this study with previous transcriptomics and proteomics studies on puberty of the same cattle breed (Brahman) but in a different population identified 392 genes in common from which some genes—<i>BRAF, GABRA2, GABR1B, GAD1, FSHR, CNGA3, PDE10A, SNAP25, ESR2, GRIA2, ORAI1, EGFR, CHRNA5, VDAC2, ACVR2B, ORAI3, CYP11A1, GRIN2A, ATP2B3, CAMK2A, PLA2G, CAMK2D and MAPK3</i>—are also part of the above-mentioned pathways. The biological functions of the positional candidate genes and their annotation to known pathways allowed integrating the results into a bigger picture of molecular mechanisms related to puberty in the hypothalamus–pituitary–ovarian axis. A reasonable number of genes, common between previous puberty studies and this study on early reproductive traits, corroborates the proposed molecular mechanisms. This study identified the polymorphism associated with early reproductive traits, and candidate genes that provided a visualization of the proposed mechanisms, coordinating the hypothalamic, pituitary, and ovarian functions for reproductive performance in Brahman cattle. |
topic |
GWAS meta-analysis gene ontology <i>Bos indicus</i> Brahman cattle fertility |
url |
https://www.mdpi.com/2073-4425/12/5/768 |
work_keys_str_mv |
AT muhammadstahir metaanalysisofheifertraitsidentifiedreproductivepathwaysinibosindicusicattle AT laerciorportoneto metaanalysisofheifertraitsidentifiedreproductivepathwaysinibosindicusicattle AT cedricgondro metaanalysisofheifertraitsidentifiedreproductivepathwaysinibosindicusicattle AT olasegebshittu metaanalysisofheifertraitsidentifiedreproductivepathwaysinibosindicusicattle AT kimberleywockner metaanalysisofheifertraitsidentifiedreproductivepathwaysinibosindicusicattle AT andrewltan metaanalysisofheifertraitsidentifiedreproductivepathwaysinibosindicusicattle AT hugorsmith metaanalysisofheifertraitsidentifiedreproductivepathwaysinibosindicusicattle AT gabrielacgouveia metaanalysisofheifertraitsidentifiedreproductivepathwaysinibosindicusicattle AT jagishkour metaanalysisofheifertraitsidentifiedreproductivepathwaysinibosindicusicattle AT marinarsfortes metaanalysisofheifertraitsidentifiedreproductivepathwaysinibosindicusicattle |
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doaj-b8571f0692a3495893c93ce7273af6692021-06-01T00:21:53ZengMDPI AGGenes2073-44252021-05-011276876810.3390/genes12050768Meta-Analysis of Heifer Traits Identified Reproductive Pathways in <i>Bos indicus</i> CattleMuhammad S. Tahir0Laercio R. Porto-Neto1Cedric Gondro2Olasege B. Shittu3Kimberley Wockner4Andre W. L. Tan5Hugo R. Smith6Gabriela C. Gouveia7Jagish Kour8Marina R. S. Fortes9School of Chemistry and Molecular Bioscience, The University of Queensland Australia, Brisbane, QLD 4072, AustraliaCommonwealth Scientific and Industrial Research Organization, Brisbane, QLD 4072, AustraliaDepartment of Animal Science, Michigan State University, East Lansing, MI 48824, USASchool of Chemistry and Molecular Bioscience, The University of Queensland Australia, Brisbane, QLD 4072, AustraliaSchool of Chemistry and Molecular Bioscience, The University of Queensland Australia, Brisbane, QLD 4072, AustraliaSchool of Chemistry and Molecular Bioscience, The University of Queensland Australia, Brisbane, QLD 4072, AustraliaSchool of Chemistry and Molecular Bioscience, The University of Queensland Australia, Brisbane, QLD 4072, AustraliaAnimal Science Department, Veterinary School, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilSchool of Chemistry and Molecular Bioscience, The University of Queensland Australia, Brisbane, QLD 4072, AustraliaSchool of Chemistry and Molecular Bioscience, The University of Queensland Australia, Brisbane, QLD 4072, AustraliaFertility traits measured early in life define the reproductive potential of heifers. Knowledge of genetics and biology can help devise genomic selection methods to improve heifer fertility. In this study, we used ~2400 Brahman cattle to perform GWAS and multi-trait meta-analysis to determine genomic regions associated with heifer fertility. Heifer traits measured were pregnancy at first mating opportunity (PREG1, a binary trait), first conception score (FCS, score 1 to 3) and rebreeding score (REB, score 1 to 3.5). The heritability estimates were 0.17 (0.03) for PREG1, 0.11 (0.05) for FCS and 0.28 (0.05) for REB. The three traits were highly genetically correlated (0.75–0.83) as expected. Meta-analysis was performed using SNP effects estimated for each of the three traits, adjusted for standard error. We identified 1359 significant SNPs (<i>p</i>-value < 9.9 × 10<sup>−6</sup> at FDR < 0.0001) in the multi-trait meta-analysis. Genomic regions of 0.5 Mb around each significant SNP from the meta-analysis were annotated to create a list of 2560 positional candidate genes. The most significant SNP was in the vicinity of a genomic region on chromosome 8, encompassing the genes <i>SLC44A1</i>, <i>FSD1L</i>, <i>FKTN</i>, <i>TAL2</i> and <i>TMEM38B</i>. The genomic region in humans that contains homologs of these genes is associated with age at puberty in girls. Top significant SNPs pointed to additional fertility-related genes, again within a 0.5 Mb region, including <i>ESR2</i>, <i>ITPR1</i>, <i>GNG2, RGS9BP, ANKRD27</i>, <i>TDRD12</i>, <i>GRM1, MTHFD1, PTGDR</i> and <i>NTNG1.</i> Functional pathway enrichment analysis resulted in many positional candidate genes relating to known fertility pathways, including GnRH signaling, estrogen signaling, progesterone mediated oocyte maturation, cAMP signaling, calcium signaling, glutamatergic signaling, focal adhesion, PI3K-AKT signaling and ovarian steroidogenesis pathway. The comparison of results from this study with previous transcriptomics and proteomics studies on puberty of the same cattle breed (Brahman) but in a different population identified 392 genes in common from which some genes—<i>BRAF, GABRA2, GABR1B, GAD1, FSHR, CNGA3, PDE10A, SNAP25, ESR2, GRIA2, ORAI1, EGFR, CHRNA5, VDAC2, ACVR2B, ORAI3, CYP11A1, GRIN2A, ATP2B3, CAMK2A, PLA2G, CAMK2D and MAPK3</i>—are also part of the above-mentioned pathways. The biological functions of the positional candidate genes and their annotation to known pathways allowed integrating the results into a bigger picture of molecular mechanisms related to puberty in the hypothalamus–pituitary–ovarian axis. A reasonable number of genes, common between previous puberty studies and this study on early reproductive traits, corroborates the proposed molecular mechanisms. This study identified the polymorphism associated with early reproductive traits, and candidate genes that provided a visualization of the proposed mechanisms, coordinating the hypothalamic, pituitary, and ovarian functions for reproductive performance in Brahman cattle.https://www.mdpi.com/2073-4425/12/5/768GWASmeta-analysisgene ontology<i>Bos indicus</i>Brahman cattlefertility |