Poster abstracts

Poster number 34 submitted by Mallory Havens

An intronic mutation in the Polycystic Kidney Disease gene, PKD1, that affects splicing and microRNA processing

Mallory A. Havens (Department of Cell Biology and Anatomy, Chicago Medical School at Rosalind Franklin University), Jennifer Akamine (Department of Cell Biology and Anatomy, Chicago Medical School at Rosalind Franklin University), Paige M. Keasler (Department of Biology at Lake Forest College), Michelle L. Hastings (Department of Cell Biology and Anatomy, Chicago Medical School at Rosalind Franklin University)

Abstract:
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common genetic disorders, affecting 1 in 500-1000 people. The disease is characterized by cyst formation on the kidneys that can lead to renal failure. The phenotypic severity of the disease varies among patients and the source of this variation is not well understood. ADPKD is caused by mutations in either the PKD1 or PKD2 gene. Our lab is characterizing a disease-associated C to T point mutation in the polypyrimidine tract of intron 45 of PKD1. Intron 45 is a mirtron—an intron that gives rise to a microRNA (miR-1225) in a splicing-dependent manner. The mutation in intron 45 may disrupt intron splicing and/or microRNA processing and targeting. Mir-1225 is predicted to target genes involved in several diseases including idiopathic kidney stones, Dent’s disease and Prader-Willi syndrome. Alterations in mir-1225 expression or activity could be a determinant of phenotypic severity in ADPKD. We find that the point mutation in intron 45 of PKD1/mir-1225 partially inhibits splicing and also leads to a reduction in mir-1225 abundance. We are currently investigating the relationship between splicing and mir-1225 expression and testing whether mir-1225 expression is altered in ADPKD patients. Understanding the consequences of this point mutation can help to elucidate the disease mechanism and potentially explain some of the variability in phenotypic severity. Furthermore, our characterization could help guide therapeutic development for disease treatment.

Keywords: MicroRNA, Polycystic Kidney Disease, splicing