Genome-wide assessment and mapping of inbreeding depression identifies candidate genes associated with semen traits in Holstein bulls

Mohammad Ghoreishifar; Seyed Milad Vahedi; Siavash Salek Ardestani; Majid Khansefid; Jennie E Pryce

doi:10.1186/s12864-023-09298-1

Genome-wide assessment and mapping of inbreeding depression identifies candidate genes associated with semen traits in Holstein bulls

BMC Genomics. 2023 May 3;24(1):230. doi: 10.1186/s12864-023-09298-1.

Authors

Mohammad Ghoreishifar^#^{1

2}, Seyed Milad Vahedi^#³, Siavash Salek Ardestani⁴, Majid Khansefid^{5

6}, Jennie E Pryce^{5

6}

Affiliations

¹ Agriculture Victoria Research, AgriBio, Centre for AgriBioscience, 5 Ring Road, Bundoora, Victoria, 3083, Australia. mohammad.ghoreishifar@agriculture.vic.gov.au.
² School of Applied Systems Biology, La Trobe University, Bundoora, Victoria, 3083, Australia. mohammad.ghoreishifar@agriculture.vic.gov.au.
³ Department of Animal Science and Aquaculture, Dalhousie University, Truro, NS, B2N5E3, Canada.
⁴ Department of Animal Science, University of Zanjan, Zanjan, 4537138791, Iran.
⁵ Agriculture Victoria Research, AgriBio, Centre for AgriBioscience, 5 Ring Road, Bundoora, Victoria, 3083, Australia.
⁶ School of Applied Systems Biology, La Trobe University, Bundoora, Victoria, 3083, Australia.

^# Contributed equally.

Abstract

Background: The reduction in phenotypic performance of a population due to mating between close relatives is called inbreeding depression. The genetic background of inbreeding depression for semen traits is poorly understood. Thus, the objectives were to estimate the effect of inbreeding and to identify genomic regions underlying inbreeding depression of semen traits including ejaculate volume (EV), sperm concentration (SC), and sperm motility (SM). The dataset comprised ~ 330 K semen records from ~ 1.5 K Holstein bulls genotyped with 50 K single nucleotide polymorphism (SNP) BeadChip. Genomic inbreeding coefficients were estimated using runs of homozygosity (i.e., F_ROH > 1 Mb) and excess of SNP homozygosity (F_SNP). The effect of inbreeding was estimated by regressing phenotypes of semen traits on inbreeding coefficients. Associated variants with inbreeding depression were also detected by regressing phenotypes on ROH state of the variants.

Results: Significant inbreeding depression was observed for SC and SM (p < 0.01). A 1% increase in F_ROH reduced SM and SC by 0.28% and 0.42% of the population mean, respectively. By splitting F_ROH into different lengths, we found significant reduction in SC and SM due to longer ROH, which is indicative of more recent inbreeding. A genome-wide association study revealed two signals positioned on BTA 8 associated with inbreeding depression of SC (p < 0.00001; FDR < 0.02). Three candidate genes of GALNTL6, HMGB2, and ADAM29, located in these regions, have established and conserved connections with reproduction and/or male fertility. Moreover, six genomic regions on BTA 3, 9, 21 and 28 were associated with SM (p < 0.0001; FDR < 0.08). These genomic regions contained genes including PRMT6, SCAPER, EDC3, and LIN28B with established connections to spermatogenesis or fertility.

Conclusions: Inbreeding depression adversely affects SC and SM, with evidence that longer ROH, or more recent inbreeding, being especially detrimental. There are genomic regions associated with semen traits that seems to be especially sensitive to homozygosity, and evidence to support some from other studies. Breeding companies may wish to consider avoiding homozygosity in these regions for potential artificial insemination sires.

Keywords: Dairy cattle; Inbreeding depression; Male fertility; Runs of homozygosity (ROH); Sperm quality.

MeSH terms

Animals
Cattle / genetics
Genome-Wide Association Study
Genotype
Homozygote
Inbreeding
Inbreeding Depression*
Male
Phenotype
Polymorphism, Single Nucleotide
Semen*
Sperm Motility