Article

Two-stage genome-wide association study identifies integrin beta 5 as having potential role in bull fertility.

Department of Animal and Dairy Sciences, Mississippi State University, Mississippi State, MS 39762, USA.
BMC Genomics (Impact Factor: 4.04). 05/2009; 10:176. DOI: 10.1186/1471-2164-10-176
Source: PubMed

ABSTRACT Fertility is one of the most critical factors controlling biological and financial performance of animal production systems and genetic improvement of lines. The objective of this study was to identify molecular defects in the sperm that are responsible for uncompensable fertility in Holstein bulls. We performed a comprehensive genome wide analysis of single nucleotide polymorphisms (SNP) for bull fertility followed by a second-stage replication in additional bulls for a restricted set of markers.
In the Phase I association study, we genotyped the genomic sperm DNA of 10 low-fertility and 10 high-fertility bulls using Bovine SNP Gene Chips containing approximately 10,000 random SNP markers. In these animals, 8,207 markers were found to be polymorphic, 97 of which were significantly associated with fertility (p < 0.01). In the Phase II study, we tested the four most significant SNP from the Phase I study in 101 low-fertility and 100 high-fertility bulls, with two SNPs (rs29024867 and rs41257187) significantly replicated. Rs29024867 corresponds to a nucleotide change of C --> G 2,190 bp 3' of the collagen type I alpha 2 gene on chromosome 4, while the rs41257187 (C --> T) is in the coding region of integrin beta 5 gene on chromosome 1. The SNP rs41257187 induces a synonymous (Proline --> Proline), suggesting disequilibrium with the true causative locus (i), but we found that the incubation of bull spermatozoa with integrin beta 5 antibodies significantly decreased the ability to fertilize oocytes. Our findings suggest that the bovine sperm integrin beta 5 protein plays a role during fertilization and could serve as a positional or functional marker of bull fertility.
We have identified molecular markers associated with bull fertility and established that at least one of the genes harboring such variation has a role in fertility. The findings are important in understanding mechanisms of uncompensatory infertility in bulls, and in other male mammals. The findings set the stage for more hypothesis-driven research aimed at discovering the role of variation in the genome that affect fertility and that can be used to identify molecular mechanisms of development.

0 Bookmarks
 · 
132 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sub-fertility is one of the most common problems observed in crossbred males, but the etiology remains unknown in most of the cases. Although proteomic differences in the spermatozoa and seminal plasma between breeds have been investigated, the possible differences at the sperm precursor cells and supporting/nourishing cells have not been studied. The present study reports the differential proteomic profile of spermatogenic and Sertoli cells in crossbred and purebred bulls. Testis was removed by unilateral castration of 12 peri-pubertal bulls (10 months age), four each from crossbred (Holstein Friesian × Tharparkar), exotic purebred [Holstein Friesian (HF)] and indigenous purebred [Tharparkar (TP)] bulls. Spermatogenic and Sertoli cells were isolated and subjected to proteomic analysis. Protein extracts from the Sertoli and spermatogenic cells of each breed were analyzed with 2-dimensional difference gel electrophoresis (2D-DIGE) and analyzed with Decyder™ software. Compared to HF, 26 protein spots were over expressed and 14 protein spots were under expressed in spermatogenic cells of crossbred bulls. Similarly, 7 protein spots were over expressed and 15 protein spots were under expressed in the spermatogenic cells of TP bulls compared to that of crossbred bulls. Out of 12 selected protein spots identified through mass spectrometry, Phosphatidyl ethanolamine binding protein was found to be over expressed in the spermatogenic cells of crossbred bulls compared to TP bulls. The protein, gamma actin was found to be over expressed in the Sertoli cells of HF bulls, whereas Speedy Protein-A was found to be over expressed in Sertoli cells of crossbred bulls. It may be concluded that certain proteomic level differences exist in sperm precursor cells and nourishing cells between breeds, which might be associated with differences in the fertility among these breeds.
    Frontiers in Cell and Developmental Biology 05/2014; 2(24). DOI:10.3389/fcell.2014.00024
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study was to screen the whole bull genome to identify markers and candidate genes underlying poor sperm motility. The analyzed data set originates from the Polish Holstein-Friesian bull population and consists of 41 case and 279 control bulls (selected from 1581 bulls). The most distinguishing trait of case group was very poor sperm motility (average 25.61%) when compared to control samples (average 72.95%). Each bull was genotyped using the Illumina BovineSNP50 BeadChip. Genome-wide association analysis was performed with the use of GoldenHelix SVS7 software. An additive model with a Cohran–Armitage test, Correlation/Trend adjusted by Bonferroni test were used to estimate the effect of Single Nucleotide Polymorphism (SNP) marker for poor sperm motility. Markers (n = 34) reached genome-wide significance. The most significant SNP were located on chromosome 24 (rs110876480), 5 (rs110827324 and rs29011704), and 1 (rs110596818), in the close vicinity of melanocortin 4 receptor (MC4R), PDZ domain containing ring finger 4 (PDZRN4) and ethanolamine kinase 1 (ETNK1), olfactory receptor 5K3-like (LOC785875) genes, respectively. For five other candidate genes located close to significant markers (in distance of ca. 1 Mb), namely alkaline phosphatase, liver/bone/kidney (ALPL), tripartite motif containing 36 (TRIM36), 3-hydroxyisobutyrate dehygrogenase (HIBADH), kelch-like 1 (KLHL1), protein kinase C, beta (PRKCB), their potential role in sperm motility was confirmed in the earlier studies. Five additional candidate genes, cystic fibrosis transmembrane conductance regulator (CFTR), insulin-like growth factor 1 receptor (IGF1R), steroid-5-alpha-reductase, alpha polypeptide 2 (SRD5A2), cation channel, sperm associated 1 (CATSPER1) calpain 1, (mu/I) large subunit (CAPN1) were suggested to be significantly associated with sperm motility or semen biochemistry. Results of the present study indicate there is a genetic complexity of poor sperm motility but also indicate there might be a causal polymorphism useful in marker-assisted selection. Identifying genomic regions associated with poor sperm motility may be very important for early recognition of a young sire as unsuitable for effective semen production in artificial insemination centers.
    Animal reproduction science 05/2014; 146(3-4). DOI:10.1016/j.anireprosci.2014.01.012 · 1.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the past decade, there have been many advances in whole-genome sequencing in domestic animals, as well as the development of "next-generation" sequencing technologies and high-throughput genotyping platforms. Consequently, these advances have led to the creation of the high-density SNP array as a state-of-the-art tool for genetics and genomics analyses of domestic animals. The emergence and utilization of SNP arrays will have significant impacts not only on the scale, speed, and expense of SNP genotyping, but also on theoretical and applied studies of quantitative genetics, population genetics and molecular evolution. The most promising applications in agriculture could be genome-wide association studies (GWAS) and genomic selection for the improvement of economically important traits. However, some challenges still face these applications, such as incorporating linkage disequilibrium (LD) information from HapMap projects, data storage, and especially appropriate statistical analyses on the high-dimensional, structured genomics data. More efforts are still needed to make better use of the high-density SNP arrays in both academic studies and industrial applications.
    Asian Australasian Journal of Animal Sciences 07/2010; 23(7). DOI:10.5713/ajas.2010.r.03 · 0.56 Impact Factor

Full-text (2 Sources)

Download
37 Downloads
Available from
May 20, 2014