Alu element

About: Alu element is a research topic. Over the lifetime, 1826 publications have been published within this topic receiving 105845 citations. The topic is also known as: ALU elements.

An Alu element-based model of human genome instability

Abstract: The human genome is strewn with repetitive sequence. An early estimate derived from the draft human genome sequence placed this repetitive content at ~45%. More detailed recent analyses have advanced the idea that the human repetitive and repeat derived contribution to the genome may be closer to 66-69%. The most commonly repeated sequence in the human genome is the Alu element. Alus make up 10.6 percent of all human DNA and have expanded to over one million copies in the human genome reproducing through a copy and paste mechanism. New Alu germline insertions are estimated to occur at a rate of 1 in 20 human births. In addition to their insertional impact, Alus have also been associated with various forms of genomic sequence disruptions including inversions, rearrangements, translocations and deletions. Chimeric Alus are frequently located at the breakpoints of these various forms of structural variations. This observation has led to the putative conclusion that chimeric Alus primarily result from the non-allelic homologous recombination between Alu elements. However, little proof is available regarding the actual mechanism(s) that catalyze this activity. This dissertation reveals a newly recognized pattern among human Alu pairs that may provide additional insight into the mechanism(s) driving chimeric Alu formation. After adjusting for directional biases associated with clustering, Alu pairs in the same orientation (direct) outnumber Alu pairs in the opposite orientation (inverted pairs) by over two percent (p<0.05). If this imbalance was generated by deletions resulting from interactions between inverted Alu elements, many chimeric Alus may have formed from the homologous repair of these deletions. This dissertation characterizes the human Alu pair imbalance and constructs an Alu-based model of human genome instability. This model was used to compare the relative instabilities of 50 human deletion-prone cancer genes and 50 randomly chosen genes. Taken as separate groups, the 50 deletion-prone cancer genes were estimated to be 58% more unstable than the 50 randomly chosen genes. This approach to estimating human gene instability may lay the foundation for comparing genetic risks unique to specific individuals, families and people groups.

The implication of Alu cDNA in the pathogenesis of ARMD.

Abstract: Age-related macular degeneration (ARMD or AMD) is a progressive, sight-threatening disease. The pathogenesis of ARMD is complex, involving many factors, such as metabolic, functional, genetic, and environmental factors. Recently, long interspersed nuclear element-1 (L1)-mediated reverse transcription (RT) of Alu RNA into cytoplasmic Alu complementary DNA (cDNA) has been associated with retinal pigment epithelium (RPE) destruction. These findings provide a strong input for a new direction in the management of ARMD, as certain human immunodeficiency virus (HIV) drugs, such as nucleoside reverse transcriptase inhibitors (NRTIs), were found to suppress inflammation and protect cells of the retina.

A novel method for eliminating repeat sequence in genome and its use in genome chips

Abstract: The present invention discloses a method for amplification by polymerase chain reaction, in which an artificial chromosome or a large DNA fragment of 50-5000kb in length is used as a template, and an Alu-specific primer is used as a primer. Said Alu-specific primer binds specifically to 5'-terminus of an Alu sequence, and extends from 3' to 5' of the Alu sequence, alternatively, said primer binds specifically to 3'-terminus of an Alu sequence, and extends from 5' to 3' of the Alu sequence. The present invention also includes the use of said method in preparing of genome chips. The amplification products obtained by the present method can eliminate the Alu repeat sequence, so non-specific background signal of a genome chip prepared by said method can be decreased dramatically.

Identification and Characterization of New Alu Element Insertion in the BRCA1 Exon 14 Associated with Hereditary Breast and Ovarian Cancer.

Abstract: Hereditary breast and ovarian cancer syndrome (HBOC) is an autosomal dominant cancer predisposition syndrome characterized by an increased risk of breast and ovarian cancers. Germline pathogenic variants in BRCA1 are found in about 7–10% of all familial breast cancers and 10% of ovarian cancers. Alu elements are the most abundant mobile DNA element in the human genome and are known to affect the human genome by different mechanisms leading to human disease. We report here the detection, by next-generation sequencing (NGS) analysis coupled with a suitable bioinformatics pipeline, of an AluYb8 element in exon 14 of the BRCA1 gene in a family with HBOC history first classified as BRCA-negative by Sanger sequencing and first NGS analysis. The c.4475_c.4476insAluYb8 mutation impacts splicing and induces the skipping of exon 14. As a result, the produced mRNA contains a premature stop, leading to the production of a short and likely non-functional protein (pAla1453Glyfs*10). Overall, our study allowed us to identify a novel pathogenic variant in BRCA1 and showed the importance of bioinformatics tool improvement and versioning.