PGI's research objective is to utilize genes we have identified in our unique lines of mice selectively bred for reproductive longevity (RL) that have a major effect on this trait. These selected lines reproduce up to 86% longer than the control lines and live through 100% more pregnancies. (Click here for more information on the colony.)

 Whole Genome Scan of PGI Lines for RL-Associated Genes

PGI used single nucleotide polymorphisms (SNPs - ‘mutations’) in a whole genome scan (WGS) of its mouse lines to identify the genes associated with reproductive longevity (RL).  Animals (703 samples) genotyped using a custom-designed panel of 8470 SNPs provided for the following contrasts:

• between the control line and selected line S1
• between the control line and selected line S2
• between high- and low-ranking animals from C x S line crosses

Click here for more information.

Development of  Breeding Markers for 

Genetic Improvement of Agricultural Species

PGI's gene discovery program in mice has provided a number of candidate genes from which a set of SNPs can be developed for validation in livestock. In partnership with the livestock breeding industry, PGI is using industry data and samples from which species-specific SNPs can be developed for use in marker-phenotype association analyses. Once identified, SNPs that show a high degree of association with RL will be combined in a breeding marker panel for each target species. This test will enable identification of genetically superior animals for this very important trait (click here for details), which is not easily manipulated using conventional breeding procedures.

A Breeding Marker Panel for Herd Life of Holstein Dairy Cattle

PGI has launched a program to develop markers for Holstein cattle for fertility and reproductive longevity. The first phase of this project has involved the development of cattle markers for 25 candidate genes for these traits and first stage validation of these markers. The second phase will involve further validation of SNPs (markers) for the genes that emerge from the initial phase. Those markers with a significant impact on fertility and RL will be combined in a commercial marker panel.

Cows and heifers can be tested with this panel in order to improve the herd replacement strategy and improve fertility and lower herd replacement rates. An increase of average herd life of the dairy cow of only one month boosts profitability per cow per year by $30-$60.

The Phase 1 Project

All of the genetic markers for 25 genes have been detected and validated (through sequencing) using pools of DNA samples from extreme animals. For each identified marker, an allele frequency for groups of ‘high/good’ animals and for groups of ‘low/poor’ animals (Semex bulls) were obtained. Eight high and low sire pools (~50 animals per pool) were created based on direct sire fertility or daughter fertility, herd life or milk production.

Gene variants (identified by the SNP markers) with high frequencies in the high/good pools and low frequencies in the low/poor pools were defined as the promising favorable gene variants. PGI has identified which of the 25 genes studied are the most relevant, which segments within these genes are the most important and which genetic markers within these segments are the most promising. (Click here for more details on the Phase 1 project)

The Phase 2 Project

In this phase, we will focus on the favorable gene variants using the most promising markers (384) from the most promising genes. Data and DNA samples from about 4,000 individual bulls and cows will be used to study the associations between these 384 most promising markers and all of the relevant fertility, longevity and production traits. The results of this association study will be used to assemble a commercial marker panel. With this panel it will be possible to identify calves, cows and bulls with high genetic value for fertility and herd life without a negative impact on production traits.

The Benefit of  PGI’s Marker Panel to the Holstein Dairy Farmer

The Problem Selection for milk production, inbreeding, increasing herd size and, in some cases, poorer environment (management, summer heat stress, etc) has resulted in a decline in fertility (non-return (NR) rates) and an increase in replacement rates.

The Solution The development of genetic markers for fertility and reproductive longevity creates an opportunity to reverse the negative genetic trend for these traits. PGI has an animal model for reproductive longevity (RL). Thirty generations of selection for RL has doubled the number of cycles per female mouse in 2 selection lines (10 litters on average) as compared to the control line (5 litters on average). Using this model, PGI has identified genes that control RL. PGI also has access to genes (including STAT5A) that impact fertility (embryo survival, NR rates) in cattle through a collaboration with the University of Wisconsin.

The Product  PGI’s commercial panel to predict fertility and stayability can be used in bull testing and selection programs and on cows by commercial producers.  The objective for commercial producers is to improve the effectiveness of the herd replacement strategy and to increase NR rates and average herd life. A marketing organization will sell the marker test, integrating it into a service to producers supporting their herd replacement strategy. The test panel will also be made available to cattle breeding organizations though a license agreement.

For additional information on the Holstein project, click here to view our PowerPoint presentation ‘Solving the Problem of High Replacement Rates in Dairy Herds’

Role for PGI Genes in Drug Discovery

PGI has initiated research to elucidate the underlying biochemical mechanisms by which its RL genes influence reproduction, as a basis for developing additional strategies to improve reproductive performance and related characteristics. We invite those interested in participating in this program to contact us at info@performancegenomics.ca. Preliminary physiological profiling studies of fundamental aspects of reproduction of both male and female PGI mice have provided evidence corroborating the difference in RL performance in biological terms. Also, both reproducing and non-reproducing mice of the selected lines are less prone to weight gain with advancing age. (Click here for details on these studies.)