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

Animal Genetics
F MenziCord Drögemüller

Abstract

Cholesterol deficiency, a new autosomal recessive inherited genetic defect in Holstein cattle, has been recently reported to have an influence on the rearing success of calves. The affected animals show unresponsive diarrhea accompanied by hypocholesterolemia and usually die within the first weeks or months of life. Here, we show that whole genome sequencing combined with the knowledge about the pedigree and inbreeding status of a livestock population facilitates the identification of the causative mutation. We resequenced the entire genomes of an affected calf and a healthy partially inbred male carrying one copy of the critical 2.24-Mb chromosome 11 segment in its ancestral state and one copy of the same segment with the cholesterol deficiency mutation. We detected a single structural variant, homozygous in the affected case and heterozygous in the non-affected carrier male. The genetic makeup of this key animal provides extremely strong support for the causality of this mutation. The mutation represents a 1.3kb insertion of a transposable LTR element (ERV2-1) in the coding sequence of the APOB gene, which leads to truncated transcripts and aberrant splicing. This finding was further supported by RNA sequencing of the liver t...Continue Reading

References

Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
Mar 20, 2015·PloS One·Alicja PacholewskaVidhya Jagannathan

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Citations

Jun 10, 2016·Journal of Veterinary Internal Medicine·T MockN Regenscheit
Jul 11, 2016·Journal of Dairy Science·J B ColeP M VanRaden
Nov 20, 2016·Annual Review of Animal Biosciences·Michael J MyersPhillip G Turfle
Jan 17, 2017·Polish Journal of Veterinary Sciences·S Kamiński, A Ruść
Dec 27, 2016·Frontiers in Veterinary Science·Eduardo Casas, Marcus E Kehrli
Jun 20, 2019·Animal Genetics·Irene Monika HäfligerCord Drögemüller
Mar 11, 2019·Journal of Dairy Science·J E LombardJ Maas
May 16, 2021·Veterinary Medicine and Science·Md Yousuf Ali KhanYi Zhang

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Methods Mentioned

BETA
PCR
electrophoresis
genotyping

Software Mentioned

igv
genomics viewer

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Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.