Abundancy of polymorphic CGG repeats in the human genome suggest a broad involvement in neurological disease

Sci Rep. 2021 Jan 28;11(1):2515. doi: 10.1038/s41598-021-82050-5.

Abstract

Expanded CGG-repeats have been linked to neurodevelopmental and neurodegenerative disorders, including the fragile X syndrome and fragile X-associated tremor/ataxia syndrome (FXTAS). We hypothesized that as of yet uncharacterised CGG-repeat expansions within the genome contribute to human disease. To catalogue the CGG-repeats, 544 human whole genomes were analyzed. In total, 6101 unique CGG-repeats were detected of which more than 93% were highly variable in repeat length. Repeats with a median size of 12 repeat units or more were always polymorphic but shorter repeats were often polymorphic, suggesting a potential intergenerational instability of the CGG region even for repeats units with a median length of four or less. 410 of the CGG repeats were associated with known neurodevelopmental disease genes or with strong candidate genes. Based on their frequency and genomic location, CGG repeats may thus be a currently overlooked cause of human disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Computational Biology / methods
  • Genetic Association Studies / methods
  • Genetic Predisposition to Disease*
  • Genome, Human*
  • Genomic Instability
  • Humans
  • Microsatellite Instability
  • Molecular Sequence Annotation
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / genetics*
  • Neurodevelopmental Disorders / genetics
  • Polymorphism, Genetic*
  • Trinucleotide Repeat Expansion*
  • Trinucleotide Repeats*