Meiotic recombination, gene conversion and mutation
Sprache des Vortragstitels:
European Society of Human Genetics
Sprache des Tagungstitel:
During meiosis the maternal and paternal genetic material is exchanged in a highly regulated process known as meiotic recombination. Recombination is initiated by the formation of double strand-breaks (DSBs), and in most organisms it is clustered in narrow regions, called recombination hotspots. The repair of DSBs reshapes the nucleotide landscape at recombination hotspots and a high number of polymorphisms accumulate at hotspots over time. In humans and mice, these polymorphisms lead to changes in affinity of PRDM9, a meiosis-specific, trans-acting protein that recognizes DNA target motifs and activates recombination hotspots. We still do not fully understand the exact molecular mechanism driving the sequence erosion at hotspots, but it has important consequences in the outcome of recombination.
We have characterized the processes re-shaping the nucleotide sequences at recombination hotspots by screening a large number of single recombination molecules. We particularly focused on de novo mutations and gene conversion events, as well as the effect of poly-A repeats of different lengths.
The repair of DSBs can lead to a biased nucleotide composition at recombination hotspots by gene conversion, which is the non-reciprocal exchange of DNA stretches of one chromosome to the other and is often associated with a higher probability of transmitting one allele over the other. At recombination hotspots, the transmission of GC over AT variants are favoured resulting over time to a higher GC content at hotspots. Similarly, we observed that longer poly-A repeats are transmitted more often than shorter repeats resulting in an insertion biased gene conversion, albeit this depends on the nature of the repeat heterology.
Sprache der Kurzfassung:
Meiotic recombination, gene conversion and mutatiion
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