Gain-of-Function Claims for Type-2-Diabetes-Associated Coding Variants in SLC16A11 Are Not Supported by the Experimental Data
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1-s2.0-S2211124719311982-main.pdf
Description
Published version
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852.73 KB
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Adobe PDF
Checksum (MD5)
95f01b1a2768004b6ab5f56880a711cf
Author(s)
Lander, Eric S.
Date Issued
October 2019
Journal
Cell reports
Publisher
Elsevier BV
Citation
Hoch, Eitan et al. “Gain-of-Function Claims for Type-2-Diabetes-Associated Coding Variants in SLC16A11 Are Not Supported by the Experimental Data.” Cell reports 29 (2019): 778-780 © 2019 The Author(s)
Version
Final published version
Abstract
Human genetic variants inSLC16A11are associatedwith increased risk of type 2 diabetes (T2D). We pre-viously identified two distinct mechanisms throughwhich co-inherited T2D-risk coding and non-codingvariants disruptSLC16A11expression and activity,thus implicating reduced SLC16A11 function as thedisease-relevant direction of effect. In a recent pub-lication,Zhao et al. (2019a)argue that humanSLC16A11 coding variants confer gain of function,basing their conclusions on phenotypic changesobserved following overexpression of mutant murineSlc16a11. However, data necessary to demonstrategain-of-function activity are not reported. Further-more, several fundamental flaws in their experi-mental system—including inaccurate modeling ofthe human variant haplotype and expression condi-tions that are not physiologically relevant—preventconclusions about T2D-risk variant effects on humanphysiology. This Matters Arising paper is in response toZhao et al. (2019a), published inCell Reports. Seealso the response byZhao et al. (2019b)in this issueofCell Reports.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2019.09.021
