Epigenetic heredity of human height

Physiological Reports

Pasquale Simeone¹ 

[1] Unit of Cancer Pathology, Department of Neuroscience and Imaging and CeSI, University “G. d'Annunzio” Foundation, Chieti Scalo, Italy

关键词: Bioinformatics;    DNA methylation;    epigenetic regulation;    genome‐wide association studies;    meta‐analysis;   

DOI  :  10.14814/phy2.12047

来源: Wiley

【 摘 要 】

Abstract

Genome-wide SNP analyses have identified genomic variants associated with adult human height. However, these only explain a fraction of human height variation, suggesting that significant information might have been systematically missed by SNP sequencing analysis. A candidate for such non-SNP-linked information is DNA methylation. Regulation by DNA methylation requires the presence of CpG islands in the promoter region of candidate genes. Seventy two of 87 (82.8%), height-associated genes were indeed found to contain CpG islands upstream of the transcription start site (USC CpG island searcher; validation: UCSC Genome Browser), which were shown to correlate with gene regulation. Consistent with this, DNA hypermethylation modules were detected in 42 height-associated genes, versus 1.5% of control genes (P = 8.0199e⁻¹⁷), as were dynamic methylation changes and gene imprinting. Epigenetic heredity thus appears to be a determinant of adult human height. Major findings in mouse models and in human genetic diseases support this model. Modulation of DNA methylation are candidate to mediate environmental influence on epigenetic traits. This may help to explain progressive height changes over multiple generations, through trans-generational heredity of progressive DNA methylation patterns.

【 授权许可】

CC BY   
© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.