LoFtool : a gene intolerance score based on loss-of-function variants in 60 706 individuals
Fadista, João LU ; Oskolkov, Nikolay LU ; Hansson, Ola LU
and Groop, Leif
LU
(2017)
In Bioinformatics
33(4).
p.471-474
- Abstract
MOTIVATION: Depletion of loss-of-function (LoF) mutations may provide a rank of genic functional intolerance and consequently susceptibility to disease.
RESULTS: Here we have studied LoF mutations in 60 706 unrelated individuals and show that the most intolerant quartile of ranked genes is enriched in rare and early onset diseases and explains 87% of de novo haploinsufficient OMIM mutations, 17% more than any other gene scoring tool. We detected particular enrichment in expression of the depleted LoF genes in brain (odds ratio = 1.5; P-value = 4.2e-07). By searching for de novo haploinsufficient mutations putatively associated with neurodevelopmental disorders in four recent studies, we were able to explain 81% of them. Taken... (More)
MOTIVATION: Depletion of loss-of-function (LoF) mutations may provide a rank of genic functional intolerance and consequently susceptibility to disease.
RESULTS: Here we have studied LoF mutations in 60 706 unrelated individuals and show that the most intolerant quartile of ranked genes is enriched in rare and early onset diseases and explains 87% of de novo haploinsufficient OMIM mutations, 17% more than any other gene scoring tool. We detected particular enrichment in expression of the depleted LoF genes in brain (odds ratio = 1.5; P-value = 4.2e-07). By searching for de novo haploinsufficient mutations putatively associated with neurodevelopmental disorders in four recent studies, we were able to explain 81% of them. Taken together, this study provides a novel gene intolerance ranking system, called LoFtool, which may help in ranking genes of interest based on their LoF intolerance and tissue expression.
AVAILABILITY AND IMPLEMENTATION: The LoFtool gene scores are available in the Supplementary data CONTACT: joaofadista@gmail.comSupplementary information: Supplementary data are available at Bioinformatics online.
(Less)
- author
- Fadista, João
LU
; Oskolkov, Nikolay
LU
; Hansson, Ola
LU
and Groop, Leif
LU
- organization
- publishing date
- 2017
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Bioinformatics
- volume
- 33
- issue
- 4
- pages
- 471 - 474
- publisher
- Oxford University Press
- external identifiers
-
- wos:000397264100001
- scopus:85020046273
- pmid:27563026
- ISSN
- 1367-4803
- DOI
- 10.1093/bioinformatics/btv602
- language
- English
- LU publication?
- yes
- id
- 7d3207be-0efd-4339-bd31-33c871c79a67
- date added to LUP
- 2016-11-14 17:06:27
- date last changed
- 2025-02-23 20:41:12
@article{7d3207be-0efd-4339-bd31-33c871c79a67,
abstract = {{<p>MOTIVATION: Depletion of loss-of-function (LoF) mutations may provide a rank of genic functional intolerance and consequently susceptibility to disease.</p><p>RESULTS: Here we have studied LoF mutations in 60 706 unrelated individuals and show that the most intolerant quartile of ranked genes is enriched in rare and early onset diseases and explains 87% of de novo haploinsufficient OMIM mutations, 17% more than any other gene scoring tool. We detected particular enrichment in expression of the depleted LoF genes in brain (odds ratio = 1.5; P-value = 4.2e-07). By searching for de novo haploinsufficient mutations putatively associated with neurodevelopmental disorders in four recent studies, we were able to explain 81% of them. Taken together, this study provides a novel gene intolerance ranking system, called LoFtool, which may help in ranking genes of interest based on their LoF intolerance and tissue expression.</p><p>AVAILABILITY AND IMPLEMENTATION: The LoFtool gene scores are available in the Supplementary data CONTACT: joaofadista@gmail.comSupplementary information: Supplementary data are available at Bioinformatics online.</p>}},
author = {{Fadista, João and Oskolkov, Nikolay and Hansson, Ola and Groop, Leif}},
issn = {{1367-4803}},
language = {{eng}},
number = {{4}},
pages = {{471--474}},
publisher = {{Oxford University Press}},
series = {{Bioinformatics}},
title = {{LoFtool : a gene intolerance score based on loss-of-function variants in 60 706 individuals}},
url = {{http://dx.doi.org/10.1093/bioinformatics/btv602}},
doi = {{10.1093/bioinformatics/btv602}},
volume = {{33}},
year = {{2017}},
}