A transposable element insertion in APOB causes cholesterol deficiency in Holstein cattle

Area of Science:

• Genetics
• Animal Science
• Molecular Biology

Background:

• Autosomal recessive inherited cholesterol deficiency impacts Holstein cattle calf rearing.
• Affected calves exhibit diarrhea, hypocholesterolemia, and high mortality rates.
• Identifying the causative mutation is crucial for breeding programs.

Purpose of the Study:

• To identify the causative genetic mutation for cholesterol deficiency in Holstein cattle.
• To understand the molecular mechanism of the identified mutation.
• To develop a diagnostic tool for genetic selection.

Main Methods:

• Whole genome sequencing of affected and carrier cattle.
• Analysis of pedigree and inbreeding status.
• RNA sequencing of affected calf liver transcriptome.

Main Results:

• A single structural variant, a 1.3kb insertion of a transposable LTR element (ERV2-1) in the APOB gene, was identified.
• This insertion causes truncated transcripts and aberrant splicing, leading to a loss of function.
• The mutation is homozygous in affected calves and heterozygous in carriers.

Conclusions:

• The identified APOB gene mutation is the cause of cholesterol deficiency in Holstein cattle.
• This finding provides a direct gene test for selection against the deleterious mutation.
• Understanding this genetic defect aids in improving cattle breeding and health.