Retrotransposable elements and human disease.

Abstract

Nearly 50% of the human genome is composed of fossils from the remains of past transposable element duplication. Mobilization continues in the genomes of extant humans but is now restricted to retrotransposons, a class of mobile elements that move via a copy and paste mechanism. Currently active retrotransposable elements include Long INterspersed Elements (LINEs), Short INterspersed Elements (SINEs) and SVA (SINE/VNTR/Alu) elements. Retrotransposons are responsible for creating genetic variation and on occasion, disease-causing mutations, within the human genome. Approximately 0.27% of all human disease mutations are attributable to retrotransposable elements. Different mechanisms of genome alteration created by retrotransposable elements include insertional mutagenesis, recombination, retrotransposition-mediated and gene conversion-mediated deletion, and 3' transduction. Although researchers in the field of human genetics have discovered many mutational mechanisms for retrotransposable elements, their contribution to genetic variation within humans is still being resolved.