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Haplotype & genomic reliability updates

Based on new findings from the Council on Dairy Cattle Breeding (CDCB), one new haplotype will be added, and two others removed, starting with December 2018 proofs. Alta Bull Search and Alta GPS will be programmed according to this new information.

A new Holstein haplotype, HH6, was recently identified in France, and is currently found in about 0.5% of animals in the US Holstein population. Mating two HH6 carriers is expected to yield a 7%-11% drop in conception rate.

Further research into the JH2 haplotype in Jerseys and the BH1 haplotype in Brown Swiss showed no significant fertility losses on matings between carriers. This, paired with the fact that researchers could find no causative mutation on these two haplotypes, means they will no longer be reported.

Gene test advancements

In addition to new and discontinued haplotypes, the reported haplotypes are also gaining accuracy. PEAK Geneticist, Doug Bjelland, compares the improved accuracy of haplotypes to locating a house on a map. The previous way of recognizing haplotypes essentially showed us which street a house is located on. Now, because of gene test advancements for causative mutations to determine haplotypes, we know exactly where on that street a house is located.

Upgraded genomic reliability

Improved genomic accuracy also extends beyond the gene test. Researchers are now using an 80k SNP chip. This means they are using nearly 80,000 markers on the genome, up from the previous 60,000 used since 2014.

The additional markers, combined with a new reference genome, give genomic predictions about a 1% – 2% improvement in reliability.

What does this mean for you?

We want to keep you up-to-date on the newest genetic findings. Updates on haplotypes and genomic accuracy are one part of that. Because the haplotype updates will be accounted for within the AltaGPS program, you can have confidence that potential carriers of two bulls will not be mated together. That means your clients are protected from any potential fertility losses that could result in mating two carriers of any given haplotype.

Improved genomic accuracy should give you, and your clients, even more confidence that genomics and genetics continue to advance at more rapid rate. It’s as important now as it ever has been, to ensure your clients select genetics according to their customized genetic plan so the progress they make aligns with their current situation and future goals.

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Haplotypes vs. genetic mutations

With August proofs, we saw a new and unique situation with two Alta sires: newly released sexed-only 11HO12240 AltaMILESTONE and G-STAR sire, 11HO11740 AltaFACET.

AltaMILESTONE’s initial genomic test told us he was free from the HH5 haplotype. However, the more extensive gene test for the causative mutation told us he is, in fact, an HH5-carrier. Similarly, AltaFACET was initially coded as free from the HH3 haplotype, but a later gene test revealed he is an HH3-carrier.

Traditionally, haplotypes are identified when animals have the same extended sequence of about 100 SNPs. Because we know there is more to this than the currently identified haplotypes, researchers are working to identify the exact causative mutations that cause early embryonic death1,2. This causative mutation is located in between two of the 100 SNPs used in the haplotype identification, but prior to finding the true causative mutation the exact location was unknown.

Over time, crossover events that occur in the DNA during sperm and egg creation can breakup and reassemble parts of an animal’s genome. That’s why we often see so much diversity in the progeny from a single mating pair.

These crossover events can also breakup that sequence of the 100 SNPs that we traditionally use to identify the haplotypes. If this happens, an animal could still have the causative mutation, but only have 40 of the 100 SNPs that would identify them as a haplotype carrier.

As researchers continue to identify the causative mutations for negative haplotypes, the specific gene tests will eventually replace the current haplotype tests used by the CDCB.

Although crossover events frequently happen in gamete formation, this process rarely occurs within the lethal haplotypes. In fact, these are the first instances of inconsistent haplotype results for Alta marketed sires.

For full disclosure, it’s important to remember that AltaMILESTONE (HH5) and AltaFACET (HH3) both have the causative mutation for their respective haplotypes and will therefore be labeled as carriers on Alta’s proof materials and website.

 

1Shutz et al. 2016. The Holstein Friesian Lethal Haplotype 5 (HH5) Results from a Complete Deletion of TBF1M and Cholesterol Deficiency (CDH) from an ERV-(LTR) Insertion into the Coding Region of APOB. PLoS ONE 11:e0154602.

2McClure et al. 2014. Bovine Exome Sequence Analysis and Targeted SNP Genotyping of Recessive Fertility Defects BH1, HH2, and HH3 Reveal a Putative Causative Mutation in SMC2 for HH3. PLoS One 9(3):e92769.

 

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