BIF 2019: Developing DNA Tests for Improved Fertility and Reduced Embryonic Loss in US Cattle Breeds

Jeremy Taylor
University of Missouri

Taylor is going to cover several things:

• GGP-F250
• Imputation
• Haplotype diversity
• Embryonic Lethals

The GGP-F250 is a very unique assay compared to other SNP panels. All of the other available assays (SNP panels) use common variants. The GGP-F250 has many rare variants, most of which are located in genes or other functional elements.

Why is rare variation important? Most of the variation in mammalian genomes, including the genomes of cattle, contain rare variation. Most of the DNA differences between different individuals are rare variants. We can't tag this rare variation with the common variants included in most SNP panels. To accurately measure genetic differences (and predict EPDs), we have to account for rare variation.

Imputation is the process of:
1. Sorting DNA variants onto each chromosome (phasing)
2. Filling in missing genotypes

We can impute from 50,000 SNPs to 700,000 SNPs to 15 million variants. But, we can't do this accurately for rare variants. However, when we include the GGP-F250 assay into this process, we can now accurately impute rare variants.

Why are imputed rare variants important? Taylor's students just re-analyzed the feed efficiency project samples. The heritability is highest when we include rare variants in the analysis. This is also seen when analyzing Bovine Respiratory Disease as well. When looking at genomic predictions (EPDs) for BRD, the predictions are more accurate when using rare variants.

Taylor then discussed genomic diversity. Genomic diversity is affected 1) by the number of DNA variants and 2) the number of combinations of these DNA variants (haplotypes, strings of variants inherited as a unit). However, we also have to account for the frequency of the different haplotypes. If 90% of the population has one haplotype, then there isn't very much diversity.

When we look at haplotype diversity weighted by frequency, Angus has the fewest number of haplotypes, followed by Brangus, Simmental, Santa Gertrudis, and Beefmaster.

In Brangus, we have selected them to be more like Angus than Brahman. There is more Angus ancestry in Brangus than expected by pedigree. Some examples of this is selection for polled and black.

As Taylor looked at haplotype diversity, he could also look for haplotypes that are never inherited in two copies. These haplotypes carry DNA variants that are embryonic lethals. Taylor repeated this analysis with varrying number of SNPs per haplotype. Taylor finds there are 122 regions in the Angus genome that possibly carry embryonic lethals. Seventy-six (76) of these regions contain genes that are know to be essential for life. These 76 regions are likely responsible for 5% of embryos lost in U.S. registered Angus.