Correlation Between Sequence Features Of Chromosomal Rearrangement And Chromosome Structure

During the study of chromosomal rearrangements, there are3important model: RandomBreakage Model, that is, rearrangement breakpoints are independently and uniformlydistributed. Fragile Breakage Model, which assumes the existence of fragile regions ingenomes and postulates that the breakpoints occur mainly within these relatively short fragileregions (hot spots of rearrangements); Intergenic Breakage Model, which is the current modelof structural genome evolution, considers that evolutionary rearrangement breakages happenwith a uniform propensity along the genome but are selected against in genes, their regulatoryregions and in-between. Moreover, Chromosomal rearrangements and copy number variants(CNVs) play key roles in genome evolution and genetic disease; however, the molecularmechanisms underlying these types of structural genomic variation are not fully understood.The availability of complete genome sequences provides, for the first time, an idealopportunity to analyze the relationship between structural genomic variation (chromosomalrearrangement and CNV) and recombination on a genome-wide level. The aims of this studywere therefore threefold:(1) through bioinformatics, we can accurately get the coordinate ofchromosomal rearrangement and copy number variation, and then we can also get thesequence of them;(2) to analyze the sequence of EBRs, confirm it position in the genome andfind if any sequence feature in this region;(3) to test the hypothesis that there is anassociation between CNV, chromosomal rearrangements, and recombination by correlatingdata from (1) and (2) with recombination rate data from a high-resolution genetic linkagemap.We applied this methodology between the genome of human and those of ten sequencedeutherian mammals which allowed us to delineate evolutionary breakpoint regions along thehuman genome with a finer resolution than obtained before. We investigated the distributionof these breakpoints with respect to genome organisation into domains of different activity. Inagreement with the Intergenic Breakage Model, we observed that breakpoints areunder-represented in genes. Surprisingly however, the density of breakpoints in small intergenes (1per Mb) appears significantly higher than in gene deserts (0.1per Mb).Moreover, we found a highly significant association of both chromosomal rearrangements andCNVs with elevated recombination rates.Chromosomal breakpoints are preferentially intergenic, which is not uniformlydistributed. It offten appear in the small intergene, lie close to the gene. Chromosomalrearrangement tend to happen in region of high transcriptional activity and replicationinitialize. So we could modify the old model, or propose a new model to describe thisphenomenon. In addition, we found that the genomic positions of both chromosomalbreakpoints and CNVs correlate to regions of high genetic recombination.