Aug 13, 2015

A computational approach to estimating nondisjunction frequency in Saccharomyces cerevisiae

BioRxiv : the Preprint Server for Biology
Daniel Chu, Sean M Burgess

Abstract

Errors segregating homologous chromosomes during meiosis result in the formation of aneuploid gametes and are the largest contributing factor to birth defects and spontaneous abortions in humans. Saccharomyces cerevisiae has long served as a model organism for studying the gene network supporting normal chromosome segregation. Current methods of measuring homolog nondisjunction frequencies are laborious and involve dissecting thousands of tetrads to detect missegregation of individually marked chromosomes. Here we describe a holistic computational approach to determine the relative contributions of meiosis I nondisjunction and random spore death in mutants with reduced spore viability. These values are based on best-fit distributions of 4, 3, 2, 1, and 0 viable-spore tetrads to observed distributions in mutant and wild-type strains. We show proof-of-principle using published data sets that the calculated average meiosis I nondisjunction frequency closely matches empirically determined values. This analysis also points to meiosis I nondisjunction as an intrinsic component of spore inviability in wild-type strains. We uncover two classes of mutants that show distinct relationships between nondisjunction death and random spore dea...Continue Reading

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Mentioned in this Paper

RAD21
Saccharomyces cerevisiae allergenic extract
Cessation of Life
Nondisjunction
Mutant Proteins
Birth
Spores, Fungal
G-Quadruplexes
Drug Interactions
Germ Cells

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