Genome‐wide association study for inhibin, luteinizing hormone, insulin‐like growth factor 1, testicular size and semen traits in bovine species

Abstract

SUMMARYThe fertility of young bulls impacts on reproduction rates, farm profit and the rate of genetic progress in beef herds. Cattle researchers and industry therefore routinely collect data on the reproductive performance of bulls. Genome-wide association studies were carried out to identify genomic regions and genes associated with reproductive traits measured during the pubertal development of Tropical Composite bulls, from 4 to 24 months of age. Data from 1 085 bulls were collected for seven traits: blood hormone levels of inhibin at 4 months (IN), luteinizing hormone following a gonadotropin releasing hormone challenge at 4 months (LH), insulin-like growth factor 1 at 6 months (IGF1), scrotal circumference at 12 months (SC), sperm motility at 18 months (MOT), percentage of normal spermatozoa at 24 months (PNS) and age at a scrotal circumference of 26 cm (AGE26, or pubertal age). Data from 729 068 single-nucleotide polymorphisms were used in the association analysis. Significant polymorphism associations were discovered for IN, IGF1, SC, AGE26 and PNS. Based on these associations, INHBE, INHBC and HELB are proposed as candidate genes for IN regulation. Polymorphisms associated with IGF1 mapped to the PLAG1 gene region, validating a reported quantitative trait locus on chromosome 14 for IGF1. The X chromosome contained most of the significant associations found for SC, AGE26 and PNS. These findings will contribute to the identification of diagnostic genetic markers and informed genomic selection strategies to assist breeding of cattle with improved fertility. Furthermore, this work provides evidence contributing to gene function annotation in the context of male fertility.

Emerging role of PLAG1 as a regulator of growth and reproduction

“…Interestingly, a number of GWASs have shown that sequence variants in the PLAG1 chromosomal region in cattle are associated not only with the growth-and reproduction-related traits discussed above but also with circulating IGF1 concentrations. The Q variant, which is associated with increased body size and higher PLAG1 expression, correlates to lower IGF1 levels in the blood and later onset of puberty (Fortes et al 2012a,b, 2013b, Hawken et al 2012. Other reproduction-related traits, such as plasma inhibin levels at 4 months of age, plasma luteinizing hormone (LH) levels following GnRH challenge at 4 months, and sperm quality, showed no obvious associations with the PLAG1 region (Fortes et al 2012b(Fortes et al , 2013b.…”

“…Bovine QQ genotypes, which show a higher expression of PLAG1, are significantly associated with lower circulating IGF1 levels in the animals (Fortes et al 2012a,b, 2013b, Hawken et al 2012. It is generally accepted that IGF1, be it of peripheral or central origin, affects the onset of puberty, which in endocrinological terms equates to the re-activation of the GnRH neurons after adolescence (DiVall et al 2010, Wolfe et al 2014.…”

“…While a role for PLAG1 in human fertility is yet to be established, GWASs have found links between puberty onset and PLAG1 (or chromosome 14) polymorphisms in cattle (Fortes et al 2012a,b, 2013a,b,c, Hawken et al 2012, Bolormaa et al 2015. A number of genetic markers for the onset of puberty mapped to the PLAG1-containing region on chromosome 14 in Brahman cows (determined as the age at which the first corpus luteum was detected) and bulls (determined as scrotal circumference or age at a scrotal circumference of 26 cm) (Fortes et al 2012a,b, 2013b, Hawken et al 2012.…”

“…The Q variant, which is associated with increased body size and higher PLAG1 expression, correlates to lower IGF1 levels in the blood and later onset of puberty (Fortes et al 2012a,b, 2013b, Hawken et al 2012. Other reproduction-related traits, such as plasma inhibin levels at 4 months of age, plasma luteinizing hormone (LH) levels following GnRH challenge at 4 months, and sperm quality, showed no obvious associations with the PLAG1 region (Fortes et al 2012b(Fortes et al , 2013b. Like always in the case of GWASs, one should bear in mind that the causality between detected polymorphisms and a phenotype cannot be deduced with certainty.…”

“…A number of genetic markers for the onset of puberty mapped to the PLAG1-containing region on chromosome 14 in Brahman cows (determined as the age at which the first corpus luteum was detected) and bulls (determined as scrotal circumference or age at a scrotal circumference of 26 cm) (Fortes et al 2012a,b, 2013b, Hawken et al 2012. Interestingly, a number of GWASs have shown that sequence variants in the PLAG1 chromosomal region in cattle are associated not only with the growth-and reproduction-related traits discussed above but also with circulating IGF1 concentrations.…”