Journal article
Analysis of the ACTN3 heterozygous genotype suggests that α-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashion
MW Hogarth, FC Garton, PJ Houweling, T Tukiainen, M Lek, DG Macarthur, JT Seto, KGR Quinlan, N Yang, SI Head, KN North
Human Molecular Genetics | Published : 2016
DOI: 10.1093/hmg/ddv613
Abstract
A common null polymorphism (R577X) in ACTN3 causes α-actinin-3 deficiency in ~18% of the global population. There is no associated disease phenotype, but α-actinin-3 deficiency is detrimental to sprint and power performance in both elite athletes and the general population. However, despite considerable investigation to date, the functional consequences of heterozygosity for ACTN3 are unclear. A subset of studies have shown an intermediate phenotype in 577RX individuals, suggesting dosedependency of α-actinin-3, while others have shown no difference between 577RR and RX genotypes. Here, we investigate the effects of α-actinin-3 expression level by comparing the muscle phenotypes of Actn3+/- ..
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Awarded by National Institutes of Health
Funding Acknowledgements
This project was funded by grants from the National Health and Medical Research Council of Australia (1002033 and 1062500). The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health. The work by TT and DGM was partially funded by the GTEx Laboratory, Data Analysis, and Coordinating Center (LDACC) contract (HHSN268201000029C) to The Broad Institute, Inc. The work by M.L. and D.G.M. was partially funded by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health, under award R01GM104371. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.