A minimal role for synonymous variation in human disease
Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved..
Synonymous mutations change the DNA sequence of a gene without affecting the amino acid sequence of the encoded protein. Although some synonymous mutations can affect RNA splicing, translational efficiency, and mRNA stability, studies in human genetics, mutagenesis screens, and other experiments and evolutionary analyses have repeatedly shown that most synonymous variants are neutral or only weakly deleterious, with some notable exceptions. Based on a recent study in yeast, there have been claims that synonymous mutations could be as important as nonsynonymous mutations in causing disease, assuming the yeast findings hold up and translate to humans. Here, we argue that there is insufficient evidence to overturn the large, coherent body of knowledge establishing the predominant neutrality of synonymous variants in the human genome.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:109 |
|---|---|
| Enthalten in: |
American journal of human genetics - 109(2022), 12 vom: 01. Dez., Seite 2105-2109 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Dhindsa, Ryan S [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 06.12.2022 Date Revised 02.06.2023 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.ajhg.2022.10.016 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM349725292 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM349725292 | ||
| 003 | DE-627 | ||
| 005 | 20231226043316.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ajhg.2022.10.016 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1165.xml |
| 035 | |a (DE-627)NLM349725292 | ||
| 035 | |a (NLM)36459978 | ||
| 035 | |a (PII)S0002-9297(22)00464-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Dhindsa, Ryan S |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A minimal role for synonymous variation in human disease |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.12.2022 | ||
| 500 | |a Date Revised 02.06.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Synonymous mutations change the DNA sequence of a gene without affecting the amino acid sequence of the encoded protein. Although some synonymous mutations can affect RNA splicing, translational efficiency, and mRNA stability, studies in human genetics, mutagenesis screens, and other experiments and evolutionary analyses have repeatedly shown that most synonymous variants are neutral or only weakly deleterious, with some notable exceptions. Based on a recent study in yeast, there have been claims that synonymous mutations could be as important as nonsynonymous mutations in causing disease, assuming the yeast findings hold up and translate to humans. Here, we argue that there is insufficient evidence to overturn the large, coherent body of knowledge establishing the predominant neutrality of synonymous variants in the human genome | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 700 | 1 | |a Wang, Quanli |e verfasserin |4 aut | |
| 700 | 1 | |a Vitsios, Dimitrios |e verfasserin |4 aut | |
| 700 | 1 | |a Burren, Oliver S |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Fengyuan |e verfasserin |4 aut | |
| 700 | 1 | |a DiCarlo, James E |e verfasserin |4 aut | |
| 700 | 1 | |a Kruglyak, Leonid |e verfasserin |4 aut | |
| 700 | 1 | |a MacArthur, Daniel G |e verfasserin |4 aut | |
| 700 | 1 | |a Hurles, Matthew E |e verfasserin |4 aut | |
| 700 | 1 | |a Petrovski, Slavé |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t American journal of human genetics |d 1949 |g 109(2022), 12 vom: 01. Dez., Seite 2105-2109 |w (DE-627)NLM000025461 |x 1537-6605 |7 nnns |
| 773 | 1 | 8 | |g volume:109 |g year:2022 |g number:12 |g day:01 |g month:12 |g pages:2105-2109 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ajhg.2022.10.016 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 109 |j 2022 |e 12 |b 01 |c 12 |h 2105-2109 | ||