The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

Evidence for 28 genetic disorders discovered by combining healthcare and research data

Evidence for 28 genetic disorders discovered by combining healthcare and research data
Evidence for 28 genetic disorders discovered by combining healthcare and research data

De novo mutations in protein-coding genes are a well-established cause of developmental disorders 1. However, genes known to be associated with developmental disorders account for only a minority of the observed excess of such de novo mutations 1,2. Here, to identify previously undescribed genes associated with developmental disorders, we integrate healthcare and research exome-sequence data from 31,058 parent–offspring trios of individuals with developmental disorders, and develop a simulation-based statistical test to identify gene-specific enrichment of de novo mutations. We identified 285 genes that were significantly associated with developmental disorders, including 28 that had not previously been robustly associated with developmental disorders. Although we detected more genes associated with developmental disorders, much of the excess of de novo mutations in protein-coding genes remains unaccounted for. Modelling suggests that more than 1,000 genes associated with developmental disorders have not yet been described, many of which are likely to be less penetrant than the currently known genes. Research access to clinical diagnostic datasets will be critical for completing the map of genes associated with developmental disorders. 

0028-0836
757–762
Kaplanis, Joanna
8eba5072-00a7-4938-9135-4e2201552ac4
Samocha, Kaitlin E.
3289b2d6-63cc-4470-a106-bd5bf6ada202
Wiel, Laurens
72015424-c55b-4500-98a5-941b13d60ec6
Lord, Jenny
e1909780-36cd-4705-b21e-4580038d4ec6
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Douglas, Andrew
2c789ec4-a222-43bc-a040-522ca64fea42
Foulds, Nicola
5e153e9f-caae-45f5-b6f0-943bd567558e
Lachlan, Katherine
175ce889-ede8-477e-93eb-afefc1af5dda
Temple, Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Wellesley, Diana
17cbd6c1-0efb-4df1-ae05-64a44987c9c0
Deciphering Developmental Disorders Study
et al.
Kaplanis, Joanna
8eba5072-00a7-4938-9135-4e2201552ac4
Samocha, Kaitlin E.
3289b2d6-63cc-4470-a106-bd5bf6ada202
Wiel, Laurens
72015424-c55b-4500-98a5-941b13d60ec6
Lord, Jenny
e1909780-36cd-4705-b21e-4580038d4ec6
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Douglas, Andrew
2c789ec4-a222-43bc-a040-522ca64fea42
Foulds, Nicola
5e153e9f-caae-45f5-b6f0-943bd567558e
Lachlan, Katherine
175ce889-ede8-477e-93eb-afefc1af5dda
Temple, Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Wellesley, Diana
17cbd6c1-0efb-4df1-ae05-64a44987c9c0

Kaplanis, Joanna, Samocha, Kaitlin E. and Wiel, Laurens , Deciphering Developmental Disorders Study and et al. (2020) Evidence for 28 genetic disorders discovered by combining healthcare and research data. Nature, 586 (7831), 757–762. (doi:10.1038/s41586-020-2832-5).

Record type: Article

Abstract

De novo mutations in protein-coding genes are a well-established cause of developmental disorders 1. However, genes known to be associated with developmental disorders account for only a minority of the observed excess of such de novo mutations 1,2. Here, to identify previously undescribed genes associated with developmental disorders, we integrate healthcare and research exome-sequence data from 31,058 parent–offspring trios of individuals with developmental disorders, and develop a simulation-based statistical test to identify gene-specific enrichment of de novo mutations. We identified 285 genes that were significantly associated with developmental disorders, including 28 that had not previously been robustly associated with developmental disorders. Although we detected more genes associated with developmental disorders, much of the excess of de novo mutations in protein-coding genes remains unaccounted for. Modelling suggests that more than 1,000 genes associated with developmental disorders have not yet been described, many of which are likely to be less penetrant than the currently known genes. Research access to clinical diagnostic datasets will be critical for completing the map of genes associated with developmental disorders. 

Text
maintext joint dnm textonly 140720 - Accepted Manuscript
Download (44kB)
Text
Kaplanis_et_al-2020-Nature - Version of Record
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 17 July 2020
e-pub ahead of print date: 14 October 2020
Published date: 14 October 2020

Identifiers

Local EPrints ID: 444844
URI: http://eprints.soton.ac.uk/id/eprint/444844
ISSN: 0028-0836
PURE UUID: 62536d10-e46d-43bd-b372-c6b479b8a9f5
ORCID for Jenny Lord: ORCID iD orcid.org/0000-0002-0539-9343
ORCID for Diana Baralle: ORCID iD orcid.org/0000-0003-3217-4833
ORCID for Andrew Douglas: ORCID iD orcid.org/0000-0001-5154-6714
ORCID for Karen Temple: ORCID iD orcid.org/0000-0002-6045-1781

Catalogue record

Date deposited: 06 Nov 2020 17:31
Last modified: 26 Nov 2021 05:39

Export record

Altmetrics

Contributors

Author: Joanna Kaplanis
Author: Kaitlin E. Samocha
Author: Laurens Wiel
Author: Jenny Lord ORCID iD
Author: Diana Baralle ORCID iD
Author: Andrew Douglas ORCID iD
Author: Nicola Foulds
Author: Katherine Lachlan
Author: Karen Temple ORCID iD
Author: Diana Wellesley
Corporate Author: Deciphering Developmental Disorders Study
Corporate Author: et al.

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×