| Title: | The contribution of X-linked coding variation to severe developmental disorders |
| Journal: | Nature Communications |
| Published: | 27 Jan 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33504798/ |
| DOI: | https://doi.org/10.1038/s41467-020-20852-3 |
| URL: | https://www.nature.com/articles/s41467-020-20852-3.pdf |
| Citations: | 38 (18 in last 2 years) as of 8 Aug 2024 |
Publication 7336
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Abstract
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.14 Keywords
- Chromosomes, Human, X
- Developmental Disabilities
- Female
- Genes, Recessive
- Genes, X-Linked
- Genetic Diseases, X-Linked
- Genetic Variation
- Humans
- Inheritance Patterns
- Male
- Multifactorial Inheritance
- Mutation
- Phenotype
- Sex Characteristics
16 Authors
- Hilary C. Martin
- Eugene J. Gardner
- Kaitlin E. Samocha
- Joanna Kaplanis
- Nadia Akawi
- Alejandro Sifrim
- Ruth Y. Eberhardt
- Ana Lisa Taylor Tavares
- Matthew D. C. Neville
- Mari E. K. Niemi
- Giuseppe Gallone
- Jeremy McRae
- Caroline F. Wright
- David R. FitzPatrick
- Helen V. Firth
- Matthew E. Hurles
1 Application
| Application ID | Title |
|---|---|
| 44165 | Investigating incomplete penetrance and the genetic architectures of human traits and diseases |
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