Smith, A.J.P., et al. PloS Genet. 8, e1002908 (2012).
The majority of genetic variation falls outside of coding sequences, in regions where it can be especially challenging to predict whether a given variant has functional consequences for the cell. To find functional clues, Smith et al. use formaldehyde-assisted isolation of regulatory elements (FAIRE), which involves cross-linking DNA to histones and then enriching for histone-depleted regions that are likely to be involved in transcription. Their strategy scans for distorted allele ratios at heterozygous loci between FAIRE-enriched and unenriched control samples. Using lymphoblastoid cell lines and commercial chips for genotyping cardiovascular genes, the researchers discovered a variant with a highly distorted allelic ratio that suggests an effect on gene regulation. They confirmed that the allele is associated with plasma cholesterol levels.
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Functional variants from chromatin changes. Nat Methods 9, 945 (2012). https://doi.org/10.1038/nmeth.2201
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DOI: https://doi.org/10.1038/nmeth.2201