Mechanisms and causality in molecular diseases.

TitleMechanisms and causality in molecular diseases.
Publication TypeJournal Article
Year of Publication2017
AuthorsKeenan, SE, Shvartsman, SY
JournalHist Philos Life Sci
Date Published2017 Oct 16
KeywordsAnemia, Sickle Cell, Genetic Diseases, Inborn, Genotype, Humans, Mutation, Phenotype, Signal Transduction

<p>How is a disease contracted, and how does it progress through the body? Answers to these questions are fundamental to understanding both basic biology and medicine. Advances in the biomedical sciences continue to provide more tools to address these fundamental questions and to uncover questions that have not been thought of before. Despite these major advances, we are still facing conceptual and technical challenges when learning about the etiology of disease, especially for genetic diseases. In this review, we illustrate this point by discussing the causal links between molecular mechanisms and systems-level phenotypes in molecular diseases. We begin with an examination of sickle cell anemia, and how mechanisms of the disease have been comprehended over the last century. While sickle cell anemia involves a mutation in a single protein in a single cell type, other diseases involve mutations in networks with many protein interactions and in diverse cell types. We introduce the challenges that result from these differences and illustrate the current obstacles by discussing the RASopathies, a recently discovered class of developmental syndromes that result from mutations in signaling networks. Methods to study mutant genotypes that lead to mutant phenotypes are discussed, particularly the use of model organisms and mutant proteins to study protein interactions that may be important for development of disease. These studies will point toward the future of diagnosing and treating genetic disease.</p>

Alternate JournalHist Philos Life Sci
PubMed ID29038918
PubMed Central IDPMC6445273
Grant ListR01 GM086537 / GM / NIGMS NIH HHS / United States