Patterns of loss of heterozygosity (LOH).

Abstract

<p>As described in the text, diploids were derived from two sequence-diverged haploids. The diploids were homozygous for the ochre suppressible <i>ade2–1</i> mutation and heterozygous for the ochre suppressor <i>SUP4-o</i> tRNA (shown as a triangle) near the left end of chromosome V or the right end of IV. Zero, one, and two copies of <i>SUP4-o</i> in the diploid produce red, pink or white colonies, respectively. The black and red lines indicate the homolog derived from the haploids YJM789 and W303–1A, respectively. The boxed chromosomes on the right side of the Fig represent recombinant products. Next to these products, we show the patterns of heterozygous markers and homozygous markers (identified by SNP arrays) as lines. Chromosome regions that are heterozygous, homozygous for W303–1A-derived SNPs, or homozygous for YJM789-derived SNPs are represented by green, red, and black segments, respectively. D1 and D2 indicate the LOH patterns in the two daughter cells that contain the recombinant products. A. Simple crossover. When the red and white sectors are examined by SNP arrays, for this type of recombination event, D1 and D2 are identical in the positions of the transition between heterozygous and homozygous SNPs. This result is expected for a crossover without an associated gene conversion. B. Crossover with a 3:1 conversion tract. In this example, when the red and white sectors are examined, the transition positions between heterozygous and homozygous SNPs are not identical. In the region that is boxed in blue, considering both sectors, three of the chromosomes have “red” SNPs and only one has “black” SNPs. C. Crossover with a 4:0 conversion. In this red/white sectored colony, there is a region adjacent to the crossover in which all four chromosomes have the “red” SNP. We interpret this pattern as resulting from the repair of two sister chromatids that are broken at the same position. It is likely that these events are a consequence of a DSB in an unreplicated chromosome that is subsequently replicated. Repair of one of the broken chromatids is associated with a conversion and a crossover, whereas the second chromatid is repaired by a conversion event unassociated with a crossover. D. BIR event. A DSB on the black chromatid is repaired by a BIR event that duplicates sequences from the red chromatid. Note that this event can be detected on any of the chromosomes, not just the one marked with the <i>SUP4-o</i> gene. E. Conversion event unassociated with a crossover. As noted in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005026#pgen.1005026.g002" target="_blank">Fig. 2D</a>, because of the high frequency of LOH events in UV-treated cells we can detect classes A to E as unselected events.</p

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