The challenges and importance of structural variation detection in livestock

Abstract

Recent studies in humans and other model organisms have demonstrated that structural variants (SVs) comprise a substantial proportion of variation among individuals of each species. Many of these variants have been linked to debilitating diseases in humans, thereby cementing the importance of refining methods for their detection. Despite progress in the field, reliable detection of SVs still remains a problem even for human subjects. Many of the underlying problems that make SVs difficult to detect in humans are amplified in livestock species, whose lower quality genome assemblies and incomplete gene annotation can often give rise to false positive SV discoveries. Regardless of the challenges, SV detection is just as important for livestock researchers as it is for human researchers, given that several productive traits and diseases have been linked to copy number variations (CNVs) in cattle, sheep, and pig. Already, there is evidence that many beneficial SVs have been artificially selected in livestock such as a duplication of the agouti signaling protein gene that causes white coat color in sheep. In this review, we will list current SV and CNV discoveries in livestock and discuss the problems that hinder routine discovery and tracking of these polymorphisms. We will also discuss the impacts of selective breeding on CNV and SV frequencies and mention how SV genotyping could be used in the future to improve genetic selection.

Genetics of Parkinson’s Disease: The Role of Copy Number Variations

“…NHEJ is more often associated with deletions and chromosomal translocations. However, complicated DNA intermediates have been proposed as origin mechanisms for duplications as well [26]. The third mechanism proposed to trigger non-recurrent genomic rearrangements is fork stalling and template switching (FoSTeS) [27].…”

“…Such template switching may occur several times before the replica-tion process gets back to its original template, resulting in complex rearrangements ( Figure 3) [25]. The pausing and stalling of the DNA replication machinery are common at certain nucleotide motifs and repetitive DNA sequences; however, such events can also occur due to chemical changes in DNA structure as DNA lesions or DNA alkylization [26]. CNVs generated by FoSTeS mainly originate during the S phase of the cell cycle as a consequence of DNA repair mechanisms.…”

“…CNVs generated by FoSTeS mainly originate during the S phase of the cell cycle as a consequence of DNA repair mechanisms. It should be noted that the CNVs created through FoSTeS are difficult to be distinguished from those generated by micro-homology-mediated breakpoint-induced repair (MMBIR), a mechanism of end-joining that relies on small-scale homology of DNA sequence at the ends of DSBs [26]. After the original stalling of the replication fork (dark blue lines), the lagging strand disengages and anneals to a second fork (green lines), followed by extension of the now 'primed' second fork and DNA synthesis.…”

Multi-Locus Genotyping of Cattle Genomes on the Bases of the Region Homology to Retrotransposons

“…To increase the efficiency of marking genomic domains the polymorphism of which could be used to solve problems of genomic selection, a new generation of markers resulting from the study on polymorphisms based on the short (less than 400 base pairs, bp) DNA fragments copy number variability (CNV) and their genomic distribution [8][9][10] is involved in SNPs. Nevertheless, these two approaches (SNP and CNV) to bovine genome multi-locus genotyping turned out not to provide unequivocal results.…”

“…There are a lot of published experimental data showing that the distribution of microsatellites (and of their inverted repeats in particular) is closely related to the transpositions of retrotransposons [7][8][9][10]. The areas of localization of retrotransposons such as LINE were also found to be frequently involved in recombination and polymorphisms associated for CNV markers [15][16][17][18].…”