Table 1.

Glossary of terms

Types of Genetic Variation
1. Single-nucleotide substitution: Describes any substitution of one nucleotide for another
 Variant terminology
  Rare: mutations
  Common: polymorphisms or SNPs. A subset of SNPs changes restriction endonuclease sites. Such polymorphisms are referred to as RFLPs
 Coding or noncoding
  Coding sequence variants may alter amino acids or lead to frameshifts in translation or premature protein termination. Coding sequence variants may also leave the amino acid encoded intact or alter gene regulation in subtle ways
  Noncoding variants may alter aspects of gene regulation and transcription (e.g., promoter activity, RNA splicing). Most noncoding variants have no identified functional effects but can be useful as genetic markers in mapping studies
Examples
  (1) APOL1 G1 variant is an allele composed of two different SNPs that alter amino acids
  (2) Many different disease-causing mutations in PKD1 alter the amino acid sequence by leading to an altered protein sequence
  (3) Common noncoding SNPs in UMOD have been found to be associated with altered risk of CKD
2. Insertions/deletions (indels): Refers to insertions or deletions of small stretches of DNA
 Examples
  (1) APOL1 G2 variant is a deletion of six nucleotides that removes two amino acids from the encoded APOL1 protein
  (2) Repeat sequences (also referred to as microsatellites and minisatellites) are tracts of DNA where short stretches of DNA are repeated multiple times (from 2 to 50 or more). These are a form of variation that was very useful in earlier genetic mapping studies because of their use as genetic markers. Rarely such repeat sequences are in coding sequence. Alterations in a microsatellite in the MUC1 gene coding sequence cause a form of autosomal dominant tubulointerstitial kidney disease
3. Structural variation: Refers to larger-scale changes or rearrangements in DNA, often visible by cytogenetic methods
 Examples
  A significant fraction of syndromic and nonsyndromic CAKUT is seen in association with structural variants
  • SNP, single-nucleotide polymorphism; CAKUT, congenital anomaly of the kidney and urinary tract.