Multitrait meta-analysis identified genomic regions associated with sexual precocity in tropical beef cattle1

Abstract

Multitrait meta-analyses are a strategy to produce more accurate genome-wide association studies, especially for complex phenotypes. We carried out a meta-analysis study for traits related to sexual precocity in tropical beef cattle (Nellore and Brahman) aiming to identify important genomic regions affecting these traits. The traits included in the analyses were age at first calving (AFC), early pregnancy (EP), age at first corpus luteum (AGECL), first postpartum anoestrus interval (PPAI), and scrotal circumference (SC). The traits AFC, EP, and SCN were measured in Nellore cattle, while AGECL, PPAI, and SCB were measured in Brahman cattle. Meta-analysis resulted in 108 significant single-nucleotide polymorphisms (SNPs), at an empirical threshold P-value of 1.39 × 10-5 (false discovery rate [FDR] < 0.05). Within 0.5 Mb of the significant SNP, candidate genes were annotated and analyzed for functional enrichment. Most of the closest genes to the SNP with higher significance in each chromosome have been associated with important roles in reproductive function. They are TSC22D2, KLF7, ARHGAP29, 7SK, MAP3K5, TLE3, WDR5, TAF3, TMEM68, PPP1R15B, NR2F2, GALR1, SUFU, and KCNU1. We did not observe any significant SNP in BTA5, BTA12, BTA17, BTA18, BTA19, BTA20, BTA22, BTA23, BTA25, and BTA28. Although the majority of significant SNPs are in BTA14, it was identified significant associations in multiple chromosomes (19 out of 29 autosomes), which is consistent with the postulation that reproductive traits are complex polygenic phenotypes. Five proposed association regions harbor the majority of the significant SNP (76%) and were distributed over four chromosomes (P < 1.39 × 10-5, FDR < 0.05): BTA2 (5.55%) from 95 to 96 Mb, BTA4 (5.55%) from 94.1 to 94.8 Mb, BTA14 (59.26%) from 24 to 25 Mb and 29 to 30 Mb, and BTA21 (5.55%) from 6.7 Mb to 11.4 Mb. These regions harbored key genes related to reproductive function. Moreover, these genes were enriched for functional groups associated with immune response, maternal-fetal tolerance, pregnancy maintenance, embryo development, fertility, and response to stress. Further studies including other breeds and precocity traits could confirm the importance of these regions and identify new candidate regions for sexual precocity in beef cattle.

Fifteen Shades of Grey: Combined Analysis of Genome-Wide SNP Data in Steppe and Mediterranean Grey Cattle Sheds New Light on the Molecular Basis of Coat Color

“…Such a large geographic distribution may be consistent with known ancient migration and admixture events during dispersal of cattle out of the domestication center [17,18,20,[55][56][57][58][59][60][61] as well as more recent historical migrations between Asia and Europe and in the Mediterranean [27,62], although admixture phenomena among wild taurine and zebuine progenitors may not be ruled out. Interestingly, we found that several of the candidate genes on BTA14 (XKR4, TMEM68, TGS1, LYN, CHCHD7, SDR16C5, PENK, TOX, RPS20, PLAG1) had been previously reported to harbor signals of selection/association in taurine/zebuine composite populations or zebuine breeds [63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. This evidence possibly supports the speculation that pigment-related gene variants and phenotypes in grey taurine cattle may represent a heritage of zebuine origin, despite the fact that, for PLAG1, an allele with major effects on body size, weight, and reproduction has been shown to be a >1000 year-old-derived allele that increased rapidly in frequency in Northwestern European B. taurus between the 16th and 18th centuries, and that was hence introgressed, towards the 19th and 20th centuries, into non-European B. taurus and Bos indicus breeds likely to increase the stature of modern cattle [79,80].…”

Genome-wide scan highlights the role of candidate genes on phenotypic plasticity for age at first calving in Nellore heifers

“…Genomic regions on BTA14 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) were identified by Fortes et al 74 harboring genes with shared effects on growth, carcass and reproductive traits, and showed a putative functional mutation. In the same region, Melo et al 55 identified genes with pleiotropic effect in reproductive traits in Nellore and Brahman cattle.…”

“…The major impact of OPRK1 in Nellore AFC is highlighted by the important biological process on negative regulation of LH secretion, which had been pointed out as a potential candidate in Brahman 53 and Nellore 54 cattle puberty. The TMEM68 gene was identified to be associated with many reproductive traits in Nellore and Brahman 55 and showed up-regulation in heifer blastocyst 56 , and is likely involved in energy metabolism and lipid turnover 57 . In addition, the sexual precocity is associated with physiological events linking major metabolic factors for the attainment of puberty 49 .…”

Whole‐genome sequence analysis reveals candidate genomic footprints and genes associated with reproductive traits in Thoroughbred horse

“…7SK is a small nuclear ribonucleoprotein-coding gene (snRNA), which plays a role in DNA transcription. Previous studies have found associations of the 7SK variants with traits related to fertility and sexual precocity in bull and cattle, respectively (Melo et al, 2018;Suchocki & Szyda, 2015). Also, it has been demonstrated that this candidate gene has an important role on the control of primordial germ cell proliferation of mouse embryos (Okamura et al, 2012).…”

“…It has been known that the frequency of double ovulation in Thoroughbred mares are more than other horse breeds (Miller & Woods, 1988;Perkins & Grimmett, 2001). Litter size Feng et al, 2011;Hanrahan et al, 2004;Nicol et al, 2009;Tang et al, 2013;Zhang et al, 2008) BRINP3 30 ENSECAG00000019926 Embryonic development (Cochran, Cole, Null, & Hansen, 2013;Obando, 2017) GRID1 1 ENSECAG00000021446 Pubertal timing (Yang et al, 2016) F ST and Pi (top 1%) SMG9 10 ENSECAG00000007334 Calving interval in dairy cattle (Machado et al, 2014) 7SK snRNA -Fertility and sexual precocity (Melo et al, 2018;Suchocki & Szyda, 2015) CSMD1 27 ENSECAG00000024680 Infertility (Lee et al, 2019) Overall, the lower reproductive performance of the Thoroughbred compared with that of the other breeds has allowed us to map candidate genes responsible for reproductive traits in horse and pave the way for better understanding of molecular basis of horse reproduction variability. In conclusion, using next-generation sequencing analysis, we identified some candidate genes under selection for reproduction performance in Thoroughbred horses.…”