Retrotransposons and Human Disease

Abstract

Retrotransposition is a ‘copy‐and‐paste’ mechanism whereby a retrotransposable element is copied from one genomic location and inserted into another genomic location, using a ribonucleic acid intermediate. The consequences of the retrotransposon‐associated alterations of the genomic landscape range from silent events to changes contributing to species‐specific and individual differences as well as a broad spectrum of diseases. Retrotransposon‐induced genetic variation can lead to inactivation or alteration of expression of critical genes via insertional mutagenesis, loss of genomic sequences through nonallelic homologous recombination or in association with de novo integration. In addition to these well‐recognised mutagenic events, some retroelements such as LINE‐1 can induce deoxyribonucleic acid double‐strand breaks that, if repaired unfaithfully, may lead to mutations. Moreover, retroelements have also contributed to generation of novel genes or functions through pseudogene formation, exonisation or shuffling of genetic material during retrotransposition. Thus, a complete understanding of their cumulative effect on any given genome or on genome evolution remains elusive. Key Concepts: Retroelements are currently active in the human genome, but only a limited number of functional loci are retrotranspositionally competent. Retrotransposition is a multistep process that requires LINE‐1 proteins and cellular factors. Human retrotransposons (LINE‐1, Alu and SVA) contribute to disease through several mechanisms. LINE‐1 ORF2 protein induces DNA double‐strand breaks, but their contribution to human disease is not yet characterised. LINE‐1 expression varies among germ line, normal somatic tissues and cancer. Retrotransposition can occur in the germ line, normal somatic tissues and cancer. There is variation in the rate of LINE‐1, Alu and SVA retrotransposition. The estimated frequency of LINE‐1‐, Alu‐ and SVA‐associated diseases is likely an underestimation of their contribution to human disease.

Sukkularetrotransposon movements in the human genome

“…Retrotransposons are a subclass of TEs [1]. They are dynamic elements in genomes and even cause genetic instability; they are classified as autonomous or non-autonomous based upon whether they encode proteins required for their retrotransposition or not [2][3][4].…”

“…The most abundant retrotransposons are the LINE-1 (L1) element, with 0.5 million copies, and the Alu element, with over 1.1 million copies. While LINE-1 elements are autonomous, Alu elements are non-autonomous [4]. In addition to the human genome, retrotransposons have been identified in many organisms, especially in the plant kingdom, particularly in cereal genomes such as barley, maize, wheat and rice.…”