Genome-wide association analysis of heifer livability and early first calving in Holstein cattle

Abstract Background The survival and fertility of heifers are critical factors for the success of dairy farms. The mortality of heifers poses a significant challenge to the management and profitability of the dairy industry. In dairy farming, achieving early first calving of heifers is also essentia...

Full description

Bibliographic Details
Main Authors: Yahui Gao, Alexis Marceau, Victoria Iqbal, Jose Antonio Torres-Vázquez, Mahesh Neupane, Jicai Jiang, George E. Liu, Li Ma
Format: Article
Language:English
Published: BMC 2023-10-01
Series:BMC Genomics
Subjects:
Online Access:https://doi.org/10.1186/s12864-023-09736-0
_version_ 1797453842260951040
author Yahui Gao
Alexis Marceau
Victoria Iqbal
Jose Antonio Torres-Vázquez
Mahesh Neupane
Jicai Jiang
George E. Liu
Li Ma
author_facet Yahui Gao
Alexis Marceau
Victoria Iqbal
Jose Antonio Torres-Vázquez
Mahesh Neupane
Jicai Jiang
George E. Liu
Li Ma
author_sort Yahui Gao
collection DOAJ
description Abstract Background The survival and fertility of heifers are critical factors for the success of dairy farms. The mortality of heifers poses a significant challenge to the management and profitability of the dairy industry. In dairy farming, achieving early first calving of heifers is also essential for optimal productivity and sustainability. Recently, Council on Dairy Cattle Breeding (CDCB) and USDA have developed new evaluations of heifer health and fertility traits. However, the genetic basis of these traits has yet to be thoroughly studied. Results Leveraging the extensive U.S dairy genomic database maintained at CDCB, we conducted large-scale GWAS analyses of two heifer traits, livability and early first calving. Despite the large sample size, we found no major QTL for heifer livability. However, we identified a major QTL in the bovine MHC region associated with early first calving. Our GO analysis based on nearby genes detected 91 significant GO terms with a large proportion related to the immune system. This QTL in the MHC region was also confirmed in the analysis of 27 K bull with imputed sequence variants. Since these traits have few major QTL, we evaluated the genome-wide distribution of GWAS signals across different functional genomics categories. For heifer livability, we observed significant enrichment in promotor and enhancer-related regions. For early calving, we found more associations in active TSS, active Elements, and Insulator. We also identified significant enrichment of CDS and conserved variants in the GWAS results of both traits. By linking GWAS results and transcriptome data from the CattleGTEx project via TWAS, we detected four and 23 significant gene-trait association pairs for heifer livability and early calving, respectively. Interestingly, we discovered six genes for early calving in the Bovine MHC region, including two genes in lymph node tissue and one gene each in blood, adipose, hypothalamus, and leukocyte. Conclusion Our large-scale GWAS analyses of two heifer traits identified a major QTL in the bovine MHC region for early first calving. Additional functional enrichment and TWAS analyses confirmed the MHC QTL with relevant biological evidence. Our results revealed the complex genetic basis of heifer health and fertility traits and indicated a potential connection between the immune system and reproduction in cattle.
first_indexed 2024-03-09T15:28:43Z
format Article
id doaj.art-df7cf82b2a1841999d8f02f410be00e3
institution Directory Open Access Journal
issn 1471-2164
language English
last_indexed 2024-03-09T15:28:43Z
publishDate 2023-10-01
publisher BMC
record_format Article
series BMC Genomics
spelling doaj.art-df7cf82b2a1841999d8f02f410be00e32023-11-26T12:25:34ZengBMCBMC Genomics1471-21642023-10-012411910.1186/s12864-023-09736-0Genome-wide association analysis of heifer livability and early first calving in Holstein cattleYahui Gao0Alexis Marceau1Victoria Iqbal2Jose Antonio Torres-Vázquez3Mahesh Neupane4Jicai Jiang5George E. Liu6Li Ma7Department of Animal and Avian Sciences, University of MarylandDepartment of Animal and Avian Sciences, University of MarylandDepartment of Animal and Avian Sciences, University of MarylandDepartment of Animal and Avian Sciences, University of MarylandAnimal Genomics and Improvement Laboratory, BARC, USDA-ARSDepartment of Animal Science, North Carolina State UniversityAnimal Genomics and Improvement Laboratory, BARC, USDA-ARSDepartment of Animal and Avian Sciences, University of MarylandAbstract Background The survival and fertility of heifers are critical factors for the success of dairy farms. The mortality of heifers poses a significant challenge to the management and profitability of the dairy industry. In dairy farming, achieving early first calving of heifers is also essential for optimal productivity and sustainability. Recently, Council on Dairy Cattle Breeding (CDCB) and USDA have developed new evaluations of heifer health and fertility traits. However, the genetic basis of these traits has yet to be thoroughly studied. Results Leveraging the extensive U.S dairy genomic database maintained at CDCB, we conducted large-scale GWAS analyses of two heifer traits, livability and early first calving. Despite the large sample size, we found no major QTL for heifer livability. However, we identified a major QTL in the bovine MHC region associated with early first calving. Our GO analysis based on nearby genes detected 91 significant GO terms with a large proportion related to the immune system. This QTL in the MHC region was also confirmed in the analysis of 27 K bull with imputed sequence variants. Since these traits have few major QTL, we evaluated the genome-wide distribution of GWAS signals across different functional genomics categories. For heifer livability, we observed significant enrichment in promotor and enhancer-related regions. For early calving, we found more associations in active TSS, active Elements, and Insulator. We also identified significant enrichment of CDS and conserved variants in the GWAS results of both traits. By linking GWAS results and transcriptome data from the CattleGTEx project via TWAS, we detected four and 23 significant gene-trait association pairs for heifer livability and early calving, respectively. Interestingly, we discovered six genes for early calving in the Bovine MHC region, including two genes in lymph node tissue and one gene each in blood, adipose, hypothalamus, and leukocyte. Conclusion Our large-scale GWAS analyses of two heifer traits identified a major QTL in the bovine MHC region for early first calving. Additional functional enrichment and TWAS analyses confirmed the MHC QTL with relevant biological evidence. Our results revealed the complex genetic basis of heifer health and fertility traits and indicated a potential connection between the immune system and reproduction in cattle.https://doi.org/10.1186/s12864-023-09736-0Dairy CattleHeiferFertilityDiseaseGWASTWAS
spellingShingle Yahui Gao
Alexis Marceau
Victoria Iqbal
Jose Antonio Torres-Vázquez
Mahesh Neupane
Jicai Jiang
George E. Liu
Li Ma
Genome-wide association analysis of heifer livability and early first calving in Holstein cattle
BMC Genomics
Dairy Cattle
Heifer
Fertility
Disease
GWAS
TWAS
title Genome-wide association analysis of heifer livability and early first calving in Holstein cattle
title_full Genome-wide association analysis of heifer livability and early first calving in Holstein cattle
title_fullStr Genome-wide association analysis of heifer livability and early first calving in Holstein cattle
title_full_unstemmed Genome-wide association analysis of heifer livability and early first calving in Holstein cattle
title_short Genome-wide association analysis of heifer livability and early first calving in Holstein cattle
title_sort genome wide association analysis of heifer livability and early first calving in holstein cattle
topic Dairy Cattle
Heifer
Fertility
Disease
GWAS
TWAS
url https://doi.org/10.1186/s12864-023-09736-0
work_keys_str_mv AT yahuigao genomewideassociationanalysisofheiferlivabilityandearlyfirstcalvinginholsteincattle
AT alexismarceau genomewideassociationanalysisofheiferlivabilityandearlyfirstcalvinginholsteincattle
AT victoriaiqbal genomewideassociationanalysisofheiferlivabilityandearlyfirstcalvinginholsteincattle
AT joseantoniotorresvazquez genomewideassociationanalysisofheiferlivabilityandearlyfirstcalvinginholsteincattle
AT maheshneupane genomewideassociationanalysisofheiferlivabilityandearlyfirstcalvinginholsteincattle
AT jicaijiang genomewideassociationanalysisofheiferlivabilityandearlyfirstcalvinginholsteincattle
AT georgeeliu genomewideassociationanalysisofheiferlivabilityandearlyfirstcalvinginholsteincattle
AT lima genomewideassociationanalysisofheiferlivabilityandearlyfirstcalvinginholsteincattle