Drosophila experiments help inform study of Menkes disease

Zlatic SA, Vrailas-Mortimer A, Gokhale A, Carey LJ, Scott E, Burch R, McCall MM, Rudin-Rush S, Davis JB, Hartwig C, Werner E, Li L, Petris M, Faundez V. Rare Disease Mechanisms Identified by Genealogical Proteomics of Copper Homeostasis Mutant Pedigrees. Cell Syst. 2018 Jan 30. pii: S2405-4712(18)30008-5. PMID: 29397366.

From the abstract: "Rare neurological diseases shed light onto universal neurobiological processes. However, molecular mechanisms connecting genetic defects to their disease phenotypes are elusive. Here, we obtain mechanistic information by comparing proteomes of cells from individuals with rare disorders with proteomes from their disease-free consanguineous relatives. ... We found connections between copper dyshomeostasis and the UCHL1/PARK5 pathway of Parkinson disease, which we validated with mitochondrial respiration and Drosophila genetics assays. We propose that our genealogical "omics" strategy can be broadly applied to identify mechanisms linking a genomic locus to its phenotypes."