Cholesterol Deficiency

 

Gene: APOB (Apolipoprotein B)

Transmission: Autosomal dominant. Complete penetration for homozygous mutant animals, incomplete penetration for heterozygous carrier animals.

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease. Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with one copy of the mutation. One or both parents of an animal with the mutation have one or two copies of the mutation. Animals with one or two copies of the mutation can pass the mutation on to their offspring.

Mutation: Insertion of a 1.3 kb endogenous virus into the APOB gene; pGly135ValfsX10, exon 5, chromosome 11 bovine

Medical systems: Metabolic, digestive

Breed: Holstein

Age of onset of symptoms: symptoms are evident soon after birth.

Cholesterol deficiency is a genetic disease in cows that interferes with the transport of cholesterol in the body, especially by lipoproteins, resulting in lower blood cholesterol levels.

Homozygous mutant animals (with two copies of the mutation) have chronic diarrhea, severe weight loss, and usually die before 6 months of age. In contrast, cattle that are heterozygous carriers (have only one copy of the DNA) for the causative mutation will often show no decline in performance, even though their blood cholesterol level is lower. Some heterozygous animals, however, may show a decrease in reproductive performance.

The insertion of an endogenous retroviral element into an exon of the APOB gene prevents transcription of part of the gene, thus affecting lipid metabolism, transport, and absorption from the digestive tract. According to a study reported in 2016, the frequency of the mutation in the population of Holsteins in Germany was 6.7%.

 

References:
OMIA link: [1965-9913]

Gross JJ, Schwinn AC, Schmitz-Hsu F, et al. (2019) The APOB loss-of-function mutation of Holstein dairy cattle does not cause a deficiency of cholesterol but decreases the capacity for cholesterol transport in circulation. J Dairy Sci 102:10564-10572. [pubmed/31477289]

Häfliger IM, Hofstetter S, Mock T, et al. (2019) APOB-associated cholesterol deficiency in Holstein cattle is not a simple recessive disease. Anim Genet 50:372-375. [pubmed/31215050]

Duff JP, Passant S, Wessels M. (2016) Cholesterol deficiency causing calf illthrift and diarrhoea. Vet Rec 178:424-5, 2016.  [pubmed/27103694]

Menzi F, Besuchet-Schmutz N, Fragnière M, et al. (2016) A transposable element insertion in APOB causes cholesterol deficiency in Holstein cattle. Anim Genet. 47(2):253-7. [pubmed/26763170]

Schütz E, Wehrhahn C, Wanjek M, 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(4):e0154602. [pubmed/4851415]

 

Contributed by: Dr. Anaïs Fournier-Leclaire, Class of 2023, Faculté de médecine vétérinaire, Université de Montréal. (Translation DWS).