The Role of Mobile Genetic Elements in the Bovine Genome

A lethal hypolipidemia with autosomal recessive mode of inheritance was recently described in Holstein Friesian Cattle.  The corresponding locus was assigned to a 2.6 Mb interval (BTA11:74.5-77.1Mb) by autozygosity mapping (Kipp et al., 2015).   We herein show that the causative mutation corresponds to the sense insertion of a ~7kb full-length bos Taurus endogenous retroviral element (BoERV) in exon 5 of the Apolipoprotein B gene (APOB), resulting in complete transcriptional termination downstream to the insertion point.

We developed the ‘LocaTER’ (Localization of Transposable Endogenous Retroviral elements) bioinformatics pipeline to identify and characterize more than 1,000 ERV insertion sites that are polymorphic in modern cattle breeds.  Underrepresentation and shifts towards lower allelic frequencies of genic (vs intergenic) sense (vs antisense) insertions testifies of their capacity to cause deleterious phenotypic effects.

We took advantage of the large ‘Damona’ whole genome sequence dataset of > 750 individuals - designed for the detection of de novo mutation - to pinpoint and validate five de novo germ-line ERV transposition events, including three genic sense insertions in GARBQ, CHST11 and CYTIP.  We estimated the average transposition rate at one event per ~50 gametes with indication of a ~4-fold higher transposition rate in males than in females. 

Intriguingly, three of the four male transposition events occurred in the germ-line of a single bull.  Moreover, two of these three de novo insertions were transmitted by the same sperm cell.  Such a striking - animal-specific - burst of de novo events may be related to interindividual variation in the genomic defense mechanisms that control the strength of repression of ERV in the germ-line.