Repository logo
 

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

Published version
Peer-reviewed

Change log

Authors

Annear, Dale J 
Vandeweyer, Geert 
Elinck, Ellen 
Sanchis-Juan, Alba 
French, Courtney E 

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.

Description

Funder: Marguerite-Marie Delacroix foundation


Funder: Fonds Wetenschappelijk Onderzoek - Vlaanderen (FWO)


Funder: NIHR BioResource


Funder: Rosetrees Trust, Newton Trust, National Institute for Health Research (NIHR) for the Cambridge Biomedical Research Centre


Funder: Methusalem-OEC grant – “GENOMED”

Keywords

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

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

11

Publisher

Springer Science and Business Media LLC