INDELs

Indels are insertions or deletions of bases in DNA or RNA sequences. They range from a single base pair to thousands of base pairs, though small indels (typically one to a few tens of base pairs) are the most common. Indels differ from single nucleotide polymorphisms (SNPs), which involve base substitutions without any insertion or deletion. In protein-coding regions, the effect of an indel depends on its length: if the number of bases added or removed is not a multiple of three, a frameshift usually alters downstream amino acids and often introduces a premature stop; if the length is a multiple of three, the indel changes the amino acid sequence without shifting the reading frame.

Indels arise through several molecular mechanisms, including replication slippage, unequal crossing over during meiosis, retrotransposon activity, and mistakes in DNA repair such as non-homologous end joining or microhomology-mediated end joining. They occur throughout the genome with varying density. Small indels frequently occur in noncoding regions and can affect regulatory elements, while larger indels are often classified as structural variants.

In population genetics, indels contribute to genetic diversity and can be neutral, deleterious, or subject to selection. Many indels are associated with human disease when they disrupt coding sequences or regulatory regions. Detection relies on sequencing and sequence alignment that accommodate gaps; accuracy has benefited from longer-read sequencing technologies and specialized indel-calling approaches, which help distinguish true indels from sequencing or alignment artifacts.