# Variation in Follicle-Stimulating Hormone Receptor Expression Is Associated with the Twinning Rate QTL Located on Bovine Chromosome 11 in Holstein Cattle

## TL;DR

This study finds that higher expression of the follicle-stimulating hormone receptor gene in Holstein cows is linked to increased twin births.

## Contribution

The study identifies differential gene expression, not coding variants, as the mechanism linking a chromosome 11 QTL to twinning rates in Holstein cattle.

## Key findings

- FSHR gene expression is significantly associated with the twinning rate QTL genotype.
- Increased FSHR expression correlates with higher twinning rates in Holstein cows.
- LHCGR gene expression is not significantly linked to the twinning rate QTL.

## Abstract

Multiple gene mapping studies have reported evidence for a gene contributing to twin births in Holstein dairy cattle on bovine chromosome 11. The identified region contains two genes which encode receptors for reproductive hormones that play critical roles in supporting development of follicles and eggs in the ovary. These gene mapping studies found no association with variants in the genes’ coding sequence and twinning rate, leading to the hypothesis that the effect is due to a difference in the expression of one of these genes. This study tested that hypothesis and found evidence that the follicle-stimulating hormone receptor gene has an elevated expression in conjunction with an increased twinning rate.

Twin births in dairy cattle present challenges for producers, resulting in increased prevalence of health issues for both cows and calves, thereby impacting profitability. Genome-wide association study (GWAS) analyses of the twinning rate in Holstein cattle have reported the most significant genomic association with twinning rate in a region containing two strong candidate genes: follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Coding-sequence variants of these genes were not associated with the twinning rate, suggesting that one of the two genes is differentially expressed in association with the twinning rate. Granulosa cells were collected from 38 Holstein cows that were selected to provide similar representation of genotypes for the twinning rate quantitative trait locus (QTL). RNA was extracted from granulosa cells and gene expression was assessed by quantitative PCR with data analyzed by the ΔΔCT method. Association of gene expression with QTL genotype was tested by the Kruskal–Wallis test with the QTL genotype based on the SNP most significantly associated with twinning rate. QTL genotype was significantly associated (p = 1.88 × 10−8) with the expression of FSHR but was not associated with LHCGR expression (p = 0.18). The increased FSHR expression was associated with an increasing copy number of the G allele and thus an increased twinning rate.