Copy number variations of the extensively amplified Y-linked genes, HSFY and ZNF280BY, in cattle and their association with male reproductive traits in Holstein bulls

Abstract

BackgroundRecent transcriptomic analysis of the bovine Y chromosome revealed at least six multi-copy protein coding gene families, including TSPY, HSFY and ZNF280BY, on the male-specific region (MSY). Previous studies indicated that the copy number variations (CNVs) of the human and bovine TSPY were associated with male fertility in men and cattle. However, the relationship between CNVs of the bovine Y-linked HSFY and ZNF280BY gene families and bull fertility has not been investigated.ResultsWe investigated the copy number (CN) of the bovine HSFY and ZNF280BY in a total of 460 bulls from 15 breeds using a quantitative PCR approach. We observed CNVs for both gene families within and between cattle breeds. The median copy number (MCN) of HSFY among all bulls was 197, ranging from 21 to 308. The MCN of ZNF280BY was 236, varying from 28 to 380. Furthermore, bulls in the Bos taurus (BTA) lineage had a significantly higher MCN (202) of HSFY than bulls in the Bos indicus (BIN) lineage (178), while taurine bulls had a significantly lower MCN (231) of ZNF280BY than indicine bulls (284). In addition, the CN of ZNF280BY was positively correlated to that of HSFY on the BTAY. Association analysis revealed that the CNVs of both HSFY and ZNF280BY were correlated negatively with testis size, while positively with sire conception rate.ConclusionThe bovine HSFY and ZNF280BY gene families have extensively expanded on the Y chromosome during evolution. The CN of both gene families varies significantly among individuals and cattle breeds. These variations were associated with testis size and bull fertility in Holstein, suggesting that the CNVs of HSFY and ZNF280BY may serve as valuable makers for male fertility selection in cattle.

Association study and expression analysis of CYP4A11 gene copy number variation in Chinese cattle

“…Consistently, PLA2G2D was found to be located in CNVR 22, whose number of repeats can significantly reduce the mRNA levels of PLA2G2D and correspondingly cause growth retardation in Chinese cattle21. Yue et al 4142. studied Holstein bulls and found that the PRAMEY copy number is negatively correlated with scrotal circumference, relative scrotal circumference, percentage of normal sperm, and nonreturn rate, and the CNVs of both HSFY and ZNF280BY are negatively correlated with testis size and positively correlated with sire conception rate.…”

Androgen levels and apoptosis in the testis during postnatal development of finasteride-treated male rat offspring

“…Some of these genes are crucial for fertility: these include AZF1 (azoospermia factor 1), BPY2 (basic protein on the Y chromosome), DAZ1 (deleted in azoospermia), TSPY (testis specific protein), UTY (ubiquitously transcribed TPR gene on the Y chromosome), SRY (sex-determining region); Y chromosome also contains so-called male-specific regions associated with increased risk of cardiovascular disease or testis and prostate cancer [46][47][48]. Most of data associated with animals male reproductive traits came from studies on mouse, less from studies on rat or cattle [49][50][51]. Also in animals, some of Y-chromosomal genes are needed for proliferation of spermatogonial stem cell and normal sperm morphology [49], some of them could be functional in rat and non-functional in mouse [50] or are highly conserved in some mammalian species [52].…”

Expansion of theHSFYgene family in pig lineages

“…Cattle also have a documented expansion of HSFY (Hamilton et al 2011; Yue et al 2014), also with no apparent corresponding HSFX expansion on the X chromosome. This opened the possibility that the amplification predated the bovine/suid divergence, and was then maintained in each lineage.…”

“…Mammalian HSFY seems present in low but variable copy number across many species, with between two and eight copies in cats (Pearks Wilkerson et al 2008; Murphy et al 2006), at least one retroposed active copy in mice (Kinoshita et al 2006) and the two active copies in humans (Tessari et al 2004) plus several pseudogene copies, one of which is found on chromosome 22. In cattle, the gene family has amplified to at least 70 copies (Hamilton et al 2011; Yue et al 2014). Recent work suggests that the amplification in cattle occurred after their divergence with sheep, and so is likely an independent amplification to that in pigs (Chang et al 2013).…”