Contemporary, yeast-based approaches to understanding human genetic variation

Abstract

Determining how genetic variation contributes to human health and disease is a critical challenge. As one of the most genetically tractable model organisms, yeast has played a central role in meeting this challenge. The advent of new technologies, including high-throughput DNA sequencing and synthesis, proteomics, and computational methods, has vastly increased the power of yeast-based approaches to determine the consequences of human genetic variation. Recent successes include systematic exploration of the effects of gene dosage, large-scale analysis of the effect of coding variation on gene function, and the use of humanized yeast to model disease. By virtue of its manipulability, small genome size, and genetic tractability, yeast is poised to help us understand human genetic variation.

The laboratory domestication of Caenorhabditis elegans

“…Many different species have these attributes. For example, the single-cell eukaryote Saccharomyces cerevisiae (baker’s yeast) is immensely powerful as a genetic model organism for conserved cellular processes [1] and for quantitative genetics using large populations [2]. The fruit fly Drosophila melanogaster contributed extensively to our understanding of signal-transduction pathways and developmental patterning [3].…”

Yeast and other lower eukaryotic organisms for studies of Vps13 proteins in health and disease

“…Due to the high evolutionary conservation of fundamental cellular processes within eukaryotes, the yeast S. cerevisiae has become a potent model organism to study the intricacies of human diseases, including neurodegenerative disorders . Furthermore, yeast is suitable for high‐throughput screening approaches to identify drugs that may be effective for the treatment of human disorders …”

“…Due to the high evolutionary conservation of fundamental cellular processes within eukaryotes, the yeast S. cerevisiae has become a potent model organism to study the intricacies of human diseases, including neurodegenerative disorders. [43][44][45][46][47][48][49][50] Furthermore, yeast is suitable for high-throughput screening approaches to identify drugs that may be effective for the treatment of human disorders. 51,52 S. cerevisiae possess a single intron-less VPS13 (YLL040C) gene encoding a Vps13 protein, which may execute many of the activities performed by different hVps13 proteins.…”

Yeast Cells Expressing the Human Mitochondrial DNA Polymerase Reveal Correlations between Polymerase Fidelity and Human Disease Progression

“…The "humanized" yeast system, with the yeast genes replaced by their human orthologs, has been developed to rapidly examine the pathology of human genetic variation, thanks to the powerful genetic tools available for yeast (32)(33)(34)(35). Here, we begin addressing important questions by developing "humanized" yeast expressing human mitochondrial DNA polymerase genes with wild-type and mutant alleles.…”