| Title: |
The contribution of X-linked coding variation to severe developmental disorders. |
| Authors: |
Martin, Hilary C; Gardner, Eugene J; Samocha, Kaitlin E; Kaplanis, Joanna; Akawi, Nadia; Sifrim, Alejandro; Eberhardt, Ruth Y; Tavares, Ana Lisa Taylor; Neville, Matthew DC; Niemi, Mari EK; Gallone, Giuseppe; McRae, Jeremy; Deciphering Developmental Disorders Study; Wright, Caroline F; FitzPatrick, David R; Firth, Helen V; Hurles, Matthew E |
| Publisher Information: |
Springer Nature; //doi.org/10.1038/s41467-020-20852-3 |
| Publication Year: |
2021 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
Chromosomes; Human; Developmental Disabilities; Female; Genes; Recessive; X-Linked; Genetic Diseases; Genetic Variation; Humans; Inheritance Patterns; Male; Multifactorial Inheritance; Mutation; Phenotype; Sex Characteristics |
| Description: |
Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Electronic; application/pdf |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/318196 |
| DOI: |
10.17863/CAM.65313 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/318196; https://doi.org/10.17863/CAM.65313 |
| Rights: |
Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.1A8ECC7D |
| Database: |
BASE |