Regan, John F.Kamitaki, NolanLegler, TinaCooper, SamanthaKlitgord, NielsKarlin-Neumann, GeorgeWong, CatherineHodges, ShawnKoehler, RyanTzonev, SvilenMcCarroll, Steven2015-04-012015Regan, J. F., N. Kamitaki, T. Legler, S. Cooper, N. Klitgord, G. Karlin-Neumann, C. Wong, et al. 2015. “A Rapid Molecular Approach for Chromosomal Phasing.” PLoS ONE 10 (3): e0118270. doi:10.1371/journal.pone.0118270. http://dx.doi.org/10.1371/journal.pone.0118270.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:14351057Determining the chromosomal phase of pairs of sequence variants – the arrangement of specific alleles as haplotypes – is a routine challenge in molecular genetics. Here we describe Drop-Phase, a molecular method for quickly ascertaining the phase of pairs of DNA sequence variants (separated by 1-200 kb) without cloning or manual single-molecule dilution. In each Drop-Phase reaction, genomic DNA segments are isolated in tens of thousands of nanoliter-sized droplets together with allele-specific fluorescence probes, in a single reaction well. Physically linked alleles partition into the same droplets, revealing their chromosomal phase in the co-distribution of fluorophores across droplets. We demonstrated the accuracy of this method by phasing members of trios (revealing 100% concordance with inheritance information), and demonstrate a common clinical application by phasing CFTR alleles at genomic distances of 11–116 kb in the genomes of cystic fibrosis patients. Drop-Phase is rapid (requiring less than 4 hours), scalable (to hundreds of samples), and effective at long genomic distances (200 kb).en-USJournal Article2015-04-0110.1371/journal.pone.0118270