Meiotic recombination hot spots and cold spots

Abstract

Meiotic recombination events are distributed unevenly throughout eukaryotic genomes. This inhomogeneity leads to distortions of genetic maps that can hinder the ability of geneticists to identify genes by map-based techniques. Various lines of evidence, particularly from studies of yeast, indicate that the distribution of recombination events might reflect, at least in part, global features of chromosome structure, such as the distribution of modified nucleosomes.

Using haplotype blocks to map human complex trait loci

“…Although this frequency bias is likely to be a minor problem if common diseases are caused by common variants (COMMON DISEASE -COMMON VARIANT HYPOTHESIS) [19], it will seriously limit the usefulness of the HapMap catalogue for diseases caused by rarer alleles [5,20]. Still, if recombination hotspot boundaries are highly specific and their location governed by cellular signals, such as sequence signatures or chromosome structure, as apparent in some organisms [21], some of the intervening block boundaries might be the same whether blocks are defined by common or rare alleles. In this regard, the genomic frequency and location specificity of recombination hotspots in humans could be key determinants of the utility of the HapMap catalogue.…”

The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae

“…The rate of meiotic recombination varies considerably at different positions in the yeast genome (1,2). This variation reflects differences in the frequency of local meiosis-specific doublestrand DNA breaks (DSBs), the recombination-initiating lesion (3,4) catalyzed by Spo11p and associated proteins (5).…”

“…This variation reflects differences in the frequency of local meiosis-specific doublestrand DNA breaks (DSBs), the recombination-initiating lesion (3,4) catalyzed by Spo11p and associated proteins (5). There are several lines of evidence that the frequency of DSBs is regulated by elements of chromatin structure rather than primary DNA sequence (2). First, recombination hotspots exhibit hypersensitivity to nucleases (6)(7)(8)(9)(10).…”

“…Second, insertion of a nucleosome-excluding sequence into the yeast genome creates a recombination hotspot (11). Third, the activity of some hotspots requires the binding of transcription factors, but not high levels of transcription (2). This result has been interpreted as indicating that chromatin modifications associated with transcription factor binding stimulate both transcription and recombination.…”

SPO11 : une activité de coupure de l’ADN indispensable à la méiose

“…Toutefois, des études menées chez la levure montrent que les cibles de Spo11 correspondent à certaines régions accessibles de la chromatine (pour revue, voir [28]) dont les spécificités ne sont pas connues. A. Peciña et al [29] ont étu-dié les propriétés de la protéine de fusion Gal4-Spo11, Gal4 portant un domaine de reconnaissance et de fixation à une séquence spécifique de l'ADN.…”