Haplotypes Impacting Fertility
What is a haplotype?
A haplotype is a stretch of chromosome or DNA that is transmitted as a unit from one generation to the next. In this case, we are talking about a set of single-nucleotide polymorphisms (SNPs) on a single chromosome that is inherited together. We often think about genes or SNPs as individual units but SNPs that are located next to each other on an individual chromosome are almost always inherited together as a unit.
What are homozygous and heterozygous?Cattle have two versions of each chromosome. One chromosome was inherited from the sire and one was inherited from the dam. The words homozygous and heterozygous are used to describe the DNA, genes or SNPs at specific points along the chromosome. Homozygous describes the situation when the DNA on each chromosome is identical. Heterozygous means the DNA on each chromosome is different at a specific site.
List of Carriers
With our growing knowledge about the bovine genome, experts have predicted for some time that we'd likely discover numerous cattle genetic defects. Human genetic researchers estimate that we each carry four or five genetic defects. It is reasonable to expect that these exist at a similar level in cattle. So, it should not be surprising that we are beginning to uncover some information about a number of new genetic conditions in the Holstein, Jersey and Brown Swiss breeds.
Recently, USDA announced the discovery of five haplotypes that appear to cause embryo loss when these haplotypes exist in the homozygous state. These were discovered by taking the full SNP50 genotype database of cows and bulls used for genomic evaluations and studying the frequency of the various haplotypes. For some haplotypes, USDA discovered no homozygous animals. Eleven of these existed at a high enough frequency in the heterozygous state that it should have been highly likely to find some homozygous individuals. USDA then studied these eleven haplotypes in more detail by analyzing conception results for the instances in their database when heterozygous sires were mated to daughters of heterozygous sires. USDA found reduced conception rates for five of the eleven haplotypes. For these five haplotypes, where USDA can't find homozygous individuals and observed reductions in conception rates in targeted matings, the findings suggest that some type of genetic defect resides in this stretch of chromosome, and results in a lethal outcome (abortions). Beginning in August for Holsteins, Jerseys and Brown Swiss, USDA will begin providing the carrier status of individual animals for these five haplotypes that impact fertility.
These genetic conditions have not been directly observed and we do not know the exact genetic or biological cause. Because of this, they've been given simple names of Holstein Haplotype 1 (HH1), Holstein Haplotype 2 (HH2), Holstein Haplotype 3 (HH3), Jersey Haplotype 1 (JH1) and Brown Swiss Haplotype 1 (BH1). These haplotypes appear to have a recessive mode of inheritance where animals with zero or one copy of the haplotype are completely normal. Those that inherit two copies of the haplotype are lost as embryos most likely early in gestation.
The impact these haplotypes have on fertility, which largely determines their economic impact, is dependent on their frequency in the population. The table below shows the frequency of each of these haplotypes and their corresponding impact on fertility. JH1 has the highest frequency and animals that are heterozygous for this haplotype could have conception rates that are reduced by 2.6 percentage points. HHI, HH2 and HH3 all have similar frequencies and their impact on fertility is less than 0.5 percentage points. It is important to realize that the negative impact of these haplotypes is already accounted for in the routinely published sire conception rate (SCR) evaluations and daughter pregnancy rate (DPR) genomic evaluations. So, if you are using these traits in selecting A.I. sires they are already avoiding or compensating for these new genetic conditions.
The Select Mating Service™ (SMS™) is an excellent tool for managing these genetic conditions, as well as for avoiding inbreeding which may result in recessive conditions. By using the SMS program, herds with at least one generation of pedigree information on their cows can include heterozygous bulls in their breeding program with less than a 1 percent chance of lost pregnancies from known genetic conditions. SMS herds that do a good job of complying with the recommended matings should continue to use the A.I. sires that best deliver the traits desired in their breeding program, regardless of their status for these new haplotypes.
All herds should avoid making inbred matings in their breeding programs. The main reason for doing this is to reduce the occurrences of recessive conditions. It is a good strategy for avoiding both the known and the unknown genetic conditions.
| Name | Source Ancestors | Haplotype Frequency | Impact on Conception Rate |
| HH1 | Pawnee Farm Arlinda Chief | 4.5% | -0.35% |
| HH2 | Willowholme Mark Anthony | 4.6% | -0.36% |
| HH3 | Glendell Arlinda Chief, Gray View Skyliner | 4.7% | -0.36% |
| JH1 | Observer Chocolate Soldier | 23.4% | -2.63% |
| BH1 | West Lawn Stretch Improver | 14.0% | -0.98% |
In Summary
- A number of haplotypes that impact fertility have been discovered by USDA.
- The research evidence for these new conditions is circumstantial, but they appear to have a recessive mode of inheritance and appear to cause embryo loss early in gestation 25 percent of the time when a heterozygous sire is mated to a heterozygous dam.
- The impact of these genetic conditions is already accounted for in genomic evaluations for DPR and in SCR evaluations for bulls with a substantial number of breedings.
- Following SMS mating recommendations is a good way to take advantage of the outstanding genetics found in sires that are heterozygous for these haplotypes without experiencing the pregnancy loss that they cause.
- Continued use of some heterozygous sires will provide a greater opportunity for higher overall genetic improvement. As industry programs gradually reduce the frequency of these haplotypes in the population, their impact will also be reduced.