ABSTRACT The transposition of mobile DNA elements has contributed to nearly half of the human genome and influenced human evolution. Members of the retrotransposable elements are still altering the human genome through their active retrotransposition and a number of these insertions have led directly to disease. They can also impact on genomic function by introducing regulatory domains potentially altering the epigenetic landscape and transcriptome. SINE-VNTR-Alus (SVAs) are the youngest of the retrotransposons and are unique to the hominids with many of the SVAs human specific. We might envisage that such human specific domains could be involved in altering expression patterns that would underpin human traits associated with, for example, higher order cognitive function. SVAs are a composite element consisting of a hexamer CCCTCT repeat, Alu-like sequence, a guanine-cytosine (GC) rich variable number tandem repeat (VNTR), a short interspersed element and poly A-tail. The structure and sequence of an SVA indicate its potential regulatory properties which include splice sites, multiple cytosine-guanine dinucleotides for methylation and runs of guanines with potential for G-quadruplex DNA formation. The differential regulation of gene expression, the response of an individual to his/her environment and predisposition to disease can all be affected by the genotype of an individual at a specific locus. SVAs have generated genetic differences between individuals whether through their presence or absence or the difference in the repeat copy number of their VNTRs, which could be a source of genetic variation that is important in modulating human behaviour and mental health. It is the ability of SVA insertions, both in the germline and in somatic cells, to affect gene expression and their contribution to genetic variation of an individual that is the focus of this review. Amongst the genes highlighted in this review are those involved in Parkinson’s disease containing SVAs within their genomic locus.
View Full Article
|