Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 10, Pages 3698-3703Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0510521103
Keywords
diabetes; functional genomics; insulin; laminin; RNA interference
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in most genome-wide linkage studies, implication of a causative disease gene often requires years of expanding the study to more families and finer mapping of the initially described region. Even after such efforts, unobtainable sample sizes can be required to make statistically meaningful conclusions about a single gene. Here we demonstrate that by adding a layer of functional biology to statistical genetic results, this process can be accelerated. The diabetes susceptibility locus (chromosome 18p11) was systematically dissected by using a cell-based secretion assay and RNA interference, and we identified laminin alpha 1 to have a role in pancreatic beta cell secretion. The screen was extended to identify laminin receptor 1 as a functional partner in regards to beta cell function. Our approach can potentially be widely used in the setting of high-throughput cellular screening of other loci to identify candidate genes.
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