Aug 11, 2014

A survey of rare epigenetic variation in 23,116 human genomes identifies disease-relevant epivariations and novel CGG expansions

bioRxiv
Xu ZhangAndrew J Sharp

Abstract

There is growing recognition that epivariations, most often recognized as promoter hypermethylation events that lead to gene silencing, are associated with a number of human diseases. However, little information exists on the prevalence and distribution of rare epigenetic variation in the human population. In order to address this, we performed a survey of methylation profiles from 23,116 individuals using the Illumina 450k array. Using a robust outlier approach, we identified 4,452 unique autosomal epivariations, including potentially inactivating promoter methylation events at 384 genes linked to human disease. For example, we observed promoter hypermethylation of BRCA1 and LDLR at population frequencies of ~1 in 3,000 and ~1 in 6,000 respectively, suggesting that epivariations may underlie a fraction of human disease which would be missed by purely sequence-based approaches. Using expression data, we confirmed that many epivariations are associated with outlier gene expression. Analysis of SNV data and monozygous twin pairs suggests that approximately two thirds of epivariations segregate in the population secondary to underlying sequence mutations, while one third are likely sproradic events that occur post-zygotically. We ...Continue Reading

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Mentioned in this Paper

Biological Markers
Embryo
Lig4
Genome
Genes
CRISPR-Cas Systems
Gene Editing
RGLG4 protein, Arabidopsis
Cell Culture Techniques
Drosophila

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