Duke University

Advanced Liquid Logic, Inc.

Vanderbilt University

Michael Hauser

Michael G Pollack

Vijay Srinivasan

Allen E Eckhardt

Zhishan Hua

Hon Lung Chu

Margaret A Pericak-Vance

Silke Schmidt

Eric Postel

Jonathan L Haines

Anita Agarwal

William K Scott

The invention is directed to a droplet actuator device and methods for integrating gel electrophoresis analysis with pre or post-analytical sample handling as well as other molecular analysis processes. Using digital microfluidics technology, the droplet actuator device and methods of the invention provide the ability to perform gel electrophoresis and liquid handling operations on a single integrated device. The integrated liquid handling operations may be used to prepare and deliver samples to the electrophoresis gel, capture and subsequently process products of the electrophoresis gel or perform additional assays on the same sample materials which are analyzed by gel electrophoresis. In one embodiment, one or more molecular assays, such as nucleic acid (e.g., DNA) quantification by real-time PCR, and one or more sample processing operations such as sample dilution is performed on a droplet actuator integrated with an electrophoresis gel. In one embodiment, an electrophoresis gel may be integrated on the top substrate of the droplet actuator.

Integrated droplet actuator for gel electrophoresis and molecular analysis

Integrated droplet actuator for gel; electrophoresis and molecular analysis

Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly whose etiology remains largely unknown. Previous studies identified chromosome 1q32 as harboring a susceptibility locus for AMD, but it was not identified. We identified a strongly associated haplotype in two independent data sets. DNA sequencing of the complement factor II gene (CFII) within this haplotype revealed a coding variant, Y402II, that significantly increases the risk for AMD with odds ratios between 2.45 and 5.57. This identifies Complement factor II as involved in pathogenesis of AMD. This single variant alone is so common that it likely explains 43 percent of AMD in older adults. In addition, we have replicated and refined previous reports implicating a coding change in LOC387715 as the second major AMD susceptibility allele. The effect of rs10490924 appears to be completely independent of the Y402H variant in the CFH gene. The joint effect of these two susceptibility genes is consistent with a multiplicative model, and together, they may explain as much as 65% of the PAR of AMD. In contrast, the effect of rs10490924 appears to be strongly modified by cigarette smoking. Smoking and LOC387715 together may explain as much as 34% of AMD. Our data indicate that variant genotypes at rs10490924 confer a substantially larger AMD risk to cigarette smokers than non-smokers. This observation is supported by traditional case-control modeling, by ordered subset linkage analysis (OSA) incorporating pack-years of cigarette smoking as a covariate, and by family-based association analysis using a more homogeneous set of families as defined by OSA.

Genetic variants increase the risk of age-related macular degeneration

Growing community of inventors

Durham, NC, United States of America

Michael Hauser