Abstract
In meiosis, the exchange of DNA between chromosomes by homologous recombination is a critical step that ensures proper chromosome segregation and increases genetic diversity. Products of recombination include reciprocal exchanges, known as crossovers, and non-reciprocal gene conversions or non-crossovers. The mechanisms underlying meiotic recombination remain elusive, largely because of the difficulty of analyzing large numbers of recombination events by traditional genetic methods. These traditional methods are increasingly being superseded by high-throughput techniques capable of surveying meiotic recombination on a genome-wide basis. Next-generation sequencing or microarray hybridization is used to genotype thousands of polymorphic markers in the progeny of hybrid yeast strains. New computational tools are needed to perform this genotyping and to find and analyze recombination events. We have developed a suite of programs, ReCombine, for using short sequence reads from next-generation sequencing experiments to genotype yeast meiotic progeny. Upon genotyping, the program CrossOver, a component of ReCombine, then detects recombination products and classifies them into categories based on the features found at each location and their distribution among the various chromatids. CrossOver is also capable of analyzing segregation data from microarray experiments or other sources. This package of programs is designed to allow even researchers without computational expertise to use high-throughput, whole-genome methods to study the molecular mechanisms of meiotic recombination.
Highlights
In sexually reproducing organisms, meiosis is the specialized type of cell division that produces haploid gametes from diploid cells
Our laboratory uses the S96 strain, which is a close relative of the common laboratory strain S288c, and YJM789, a strain originally isolated from the lung of an AIDS patient [19]
Both strains have been fully sequenced by traditional methods, and their sequences differ by 0.6%, with the differences consisting of,60,000 single-nucleotide single-nucleotide polymorphisms (SNPs) and,6,000 indels [20]
Summary
Meiosis is the specialized type of cell division that produces haploid gametes (eggs and sperm, in humans) from diploid cells. During the first meiotic division, pairs of homologous chromosomes become physically linked, and DNA is exchanged between chromosomes by homologous recombination. This exchange of DNA can either be reciprocal, leading to a crossover (CO), or non-reciprocal, giving rise to a non-crossover (NCO) or gene conversion (GC). Errors in recombination can give rise to aneuploid gametes (containing too many or too few chromosomes), or to deleterious chromosomal rearrangements. Such errors are common causes of infertility and birth defects in humans [2]
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