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The majority of SNPs (94%, 128/136) present in the 17q21 asthma-risk haploblock are located in intronic or intergenic non-coding sequences (non-coding SNPs, ncSNPs) whose cell-specific cis-regulatory potential has not been fully characterized (Fig. 1a,b); as a result, the specific cell type that is most affected by the 17q21 asthma-risk variants is largely unknown.
Detecting DNA fragments that preferentially interact together on the basis of their proximity in the three-dimensional (3D) space was first used in 1993 (Ref. 135) and subsequently improved and expanded in 2002 (Ref. 136) to form the basis of all chromosome conformation capture (3C) technologies, including Hi-C (a high-throughput derivative of 3C)13. The first step of most 3C-based methods involves the formaldehyde crosslinking of cells.
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