Large differences in proportions of harmful and benign amino acid substitutions between proteins and diseases
Schaafsma, Gerard C.P. LU
and Vihinen, Mauno
LU
(2017)
In Human Mutation
38(7).
p.839-848
- Abstract
Genes and proteins are known to have differences in their sensitivity to alterations. Despite numerous sequencing studies, proportions of harmful and harmless substitutions are not known for proteins and groups of proteins. To address this question, we predicted the outcome for all possible single amino acid substitutions (AASs) in nine representative protein groups by using the PON-P2 method. The effects on 996 proteins were studied and vast differences were noticed. Proteins in the cancer group harbor the largest proportion of harmful variants (42.1%), whereas the non-disease group of proteins not known to have a disease association and not involved in the housekeeping functions had the lowest number of harmful variants (4.2%).... (More)
Genes and proteins are known to have differences in their sensitivity to alterations. Despite numerous sequencing studies, proportions of harmful and harmless substitutions are not known for proteins and groups of proteins. To address this question, we predicted the outcome for all possible single amino acid substitutions (AASs) in nine representative protein groups by using the PON-P2 method. The effects on 996 proteins were studied and vast differences were noticed. Proteins in the cancer group harbor the largest proportion of harmful variants (42.1%), whereas the non-disease group of proteins not known to have a disease association and not involved in the housekeeping functions had the lowest number of harmful variants (4.2%). Differences in the proportions of the harmful and benign variants are wide within each group, but they still show clear differences between the groups. Frequently appearing protein domains show a wide spectrum of variant frequencies, whereas no major protein structural class-specific differences were noticed. AAS types in the original and variant residues showed distinctive patterns, which are shared by all the protein groups. The observations are relevant for understanding genetic bases of diseases, variation interpretation, and for the development of methods for that purpose.
(Less)
- author
- Schaafsma, Gerard C.P.
LU
and Vihinen, Mauno
LU
- organization
- publishing date
- 2017
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Disease groups, Pathogenicity, Proteins, Sensitivity, Variation
- in
- Human Mutation
- volume
- 38
- issue
- 7
- pages
- 839 - 848
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:28444810
- wos:000403352100009
- scopus:85019655452
- ISSN
- 1059-7794
- DOI
- 10.1002/humu.23236
- language
- English
- LU publication?
- yes
- id
- 49b034a2-b7f3-4add-9665-afcafd0637fd
- date added to LUP
- 2017-06-16 14:23:45
- date last changed
- 2024-01-13 23:11:48
@article{49b034a2-b7f3-4add-9665-afcafd0637fd,
abstract = {{<p>Genes and proteins are known to have differences in their sensitivity to alterations. Despite numerous sequencing studies, proportions of harmful and harmless substitutions are not known for proteins and groups of proteins. To address this question, we predicted the outcome for all possible single amino acid substitutions (AASs) in nine representative protein groups by using the PON-P2 method. The effects on 996 proteins were studied and vast differences were noticed. Proteins in the cancer group harbor the largest proportion of harmful variants (42.1%), whereas the non-disease group of proteins not known to have a disease association and not involved in the housekeeping functions had the lowest number of harmful variants (4.2%). Differences in the proportions of the harmful and benign variants are wide within each group, but they still show clear differences between the groups. Frequently appearing protein domains show a wide spectrum of variant frequencies, whereas no major protein structural class-specific differences were noticed. AAS types in the original and variant residues showed distinctive patterns, which are shared by all the protein groups. The observations are relevant for understanding genetic bases of diseases, variation interpretation, and for the development of methods for that purpose.</p>}},
author = {{Schaafsma, Gerard C.P. and Vihinen, Mauno}},
issn = {{1059-7794}},
keywords = {{Disease groups; Pathogenicity; Proteins; Sensitivity; Variation}},
language = {{eng}},
number = {{7}},
pages = {{839--848}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Human Mutation}},
title = {{Large differences in proportions of harmful and benign amino acid substitutions between proteins and diseases}},
url = {{http://dx.doi.org/10.1002/humu.23236}},
doi = {{10.1002/humu.23236}},
volume = {{38}},
year = {{2017}},
}