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♦ Haplotype for Cholesterol Deficiency
♦ Haplotype for Cholesterol Deficiency

Researchers Discover Holstein Haplotype for Cholesterol Deficiency

Announced at the July 2015 Interbull annual meeting was evidence from Germany’s data collection center of a new genetic condition in Holsteins. This new haplotype has been labeled as “Haplotype for Cholesterol Deficiency” or HCD. USDA-AGIL (Animal Genomics and Improvement Laboratory) confirmed the findings on this genetic defect.

• How is HCD expressed by offspring?
HCD is not expressed in the same manner as other lethal recessives or haplotypes affecting fertility, which are associated with early embryonic death. Instead, calves that are homozygous for HCD - those that inherit the undesirable gene from both parents - are born alive. The homozygous calves have a disorder in cholesterol metabolism, which results in weight loss, loss of appetite, physical weakness, and chronic scours that do not respond to therapeutic treatments. This significantly affects calf vitality and survival, and most homozygous animals die within the first 6 months of life, with few living to 2 years of age.

What family lines and ancestors have been identified as HCD carriers?
Researchers have traced the defective haplotype to the Holstein bull Maughlin Storm, born in 1991. Storm is the oldest common genotyped sire that carries the defect and is therefore, considered the founder animal. Storm’s most notable descendant is Braedale Goldwyn.

Determining carrier status for HCD has, however, proven to be complicated. The Holstein bull Willowholme Mark Anthony, born in 1975, possesses the same haplotype as Storm, but Mark Anthony does not carry the specific undesirable lethal gene. The pedigrees of Mark Anthony and Storm both trace back to Fairlea Royal Mark. (Royal Mark is the sire of Mark Anthony and the maternal great-grandsire of Storm.) It is thought a mutation occurred in the three generations between Royal Mark and Storm. That mutation caused the genetic defect to be evident in Storm but not Mark Anthony.

Mark Anthony must possess a non-lethal version of the haplotype because the following bulls received his haplotype through their maternal lines, and homozygous HCD calves descending from these bulls live normal lives: Comestar Leader, Comestar Lee, Comestar Lheros and Comestar Outside.

How is HCD carrier status determined?
Storm and Mark Anthony possess the same haplotype (a haplotype is a set of closely linked genes present on one chromosome which tend to be inherited together), but only Storm possesses the specific undesirable gene. Therefore HCD status is easy to determine for animals with only Storm in their pedigree; it is more difficult to determine status if both Storm and Mark Anthony appear in the pedigree. Several organizations are cooperating to improve the precision of tracing HCD.

How are bull labels to be interpreted?
The U.S., Canada, Italy and Great Britain have proposed the following five codes and descriptions for reporting HCD: 0=Non-Carrier, 1=Carrier: (confirmed with pedigree), 2=Homozygous: (confirmed on both sides of pedigree), 3= Suspect carrier: (haplotype origin could not be confirmed from pedigree), 4=Suspect homozygous: (probable carrier and may be homozygous; origin of haplotypes could not be confirmed from pedigree). With continued research, the ability to reduce the categories and determine status with greater certainty will improve.

How will Genex provide bulls’ HCD status?
The list of active Genex bulls that are HCD carriers or suspected carriers is available here. Also available are lists of all active Genex sires by NAAB stud code with their HCD status. In the future, HCD carriers or suspect status will also be noted on the individual sire web pages.

What are the next steps in examining the impact of HCD?
At this point, researchers have not determined the precise DNA section responsible for the observed cholesterol deficiency; however it is on Chromosome 11. It is unknown whether HCD is caused by a simple mutation, deletion, other structural change in DNA or if one or more genes are involved.

Futhermore, as researchers gain a better understanding of the condition’s economic impact, HCD could be upgraded from haplotype status to an undesirable genetic recessive (calf losses have more economic impact than haplotypes that cause early embryonic loss).

Should knowledge of HCD change breeding strategies?
Animals considered heterozygous for HCD appear normal. But if a carrier is mated to another carrier, it is expected that one in four progeny would inherit two copies of the HCD haplotype and show phenotypic signs (calf mortality or decreased vitality). The approach of attempting to eradicate every animal with HCD is not recommended at this time as there is much to learn about the economic impact. Dairy cattle geneticists recommend avoiding recessive defects by using sound science and mating programs.

What other haplotypes have already been discovered?
The other Holstein haplotypes - often referred to as haplotypes affecting fertility - are known as HH1, HH2, HH3, HH4 and HH5. The Jersey breed has haplotypes 1 and 2 (JH1, JH2), Brown Swiss have BH1 and BH2, and Ayrshires have only AH1. More specific information about these previously discovered haplotypes can also be found at