A reference catalog of DNA palindromes in the human genome and their variations in 1000 Genomes

摘要

A palindrome in DNA is like a palindrome in language, but when read backwards, it is a complement of the forward sequence; effectively, the two halves of a sequence complement each other from its midpoint like in a double strand of DNA. Palindromes are distributed throughout the human genome and play significant roles in gene expression and regulation. Palindromic mutations are linked to many human diseases, such as neuronal disorders, mental retardation, and various cancers. In this work, we computed and analyzed the palindromic sequences in the human genome and studied their conservation in personal genomes using 1000 Genomes data. We found that ~30% of the palindromes exhibit variation, some of which are caused by rare variants. The analysis of disease/trait-associated single-nucleotide polymorphisms in palindromic regions showed that disease-associated risk variants are 14 times more likely to be present in palindromic regions than in other regions. The catalog of palindromes in the reference genome and 1000 Genomes is being made available here with details on their variations in each individual genome to serve as a resource for future and retrospective whole-genome studies identifying statistically significant palindrome variations associated with diseases or traits and their roles in disease mechanisms. A toolkit to detect DNA patterns has pinpointed millions of palindromes within the human genome, which could further the understanding of their association with disease. Madhavi K. Ganapathiraju of the University of Pittsburgh and colleagues used their Biological Language Modelling Toolkit to mine the human reference genome and the genomes of 2504 individuals from the 1000 Genomes project for palindromes: DNA sequences with two complementary halves, where folding at the midpoint leads to complementary base pairs lining up with each other. They identified their locations and lengths and looked for known disease-associated genetic variants, called single nucleotide polymorphisms, within them. They found links to diseases such as diabetes, obesity, Alzheimer’s disease, Crohn’s disease, and some cancers. The data was compiled into the Catalog of Palindromic Sequences to serve as a resource for investigating palindromic variations associated with disease.