Roles and Implications of Palindromic DNA in Alzheimer's Disease: A Systematic Review and Computational Analysis

Abstract

AbstractBackgroundA palindrome in DNA is a sequence consisting of two adjacent identical or highly similar inverted repeats. Palindromes are distributed throughout the genome and play important roles in gene expression and regulation. Palindromic mutations are linked to many disease states, such as neuronal disorders, mental retardation, and various cancers.MethodA systematic review was conducted in which existing literature on the palindromic DNA within disease‐associated loci of AD is synthesised. Subsequent computational analysis of DNA palindromes within promoters, introns, and exons were characterised and discussed.ResultStudies included in the review identified palindromes and palindrome‐altering in the causative genes associated with AD, which may influence the fine tuning of APP and PSEN gene expression and/or alternative splicing of the transcript, leading to their different susceptibilities to beta‐amyloidosis. Results of computational analysis suggested roles in transcription factor binding and regulatory control within promoters, alongside implications for vulnerability of palindromic regions to genomic variation within introns. Mutations in intronic regions may introduce novel regulatory activity and affect splice sites. Comparisons with the mice genome showed differential tolerance of longer unstable palindromic sequences.ConclusionOverall, the results from this study serve as a resource of identified AD‐associated palindromic sequences, which could affect various cellular processes leading to gene dysregulation and AD pathogenesis. Further research is warranted to enlighten their roles in the specific disease mechanism.