Biology subjects

Wirtz, J.

Publications and source records attributed to Wirtz, J..

2 recordsLinked to original sources

bioRxiv2018

Interdependence of linkage disequilibrium, chromatin architecture and compositional genome organization of mammals

Recent investigation established a link between DNA sequences and chromatin architecture and explained the evolutionary conservation of TADs (Topologically Associated Domains) and LADs (Lamina Associated Domains) in mammals. This prompted us to analyse the relationship between chromatin architecture and recombination landscapes of human and mouse. The results revealed that: (1) Blocks of elevated linkage disequilibrium tend to coincide with TADs and isochores, indicating co-evolving regulatory elements and genes in insulated neighbourhood; (2) double strand break (DSB) and recombination frequencies increase in GC-rich TADs, whereas recombination cold spots are typical of LADs; (3) binding and loading of proteins which are critical for DSB and meiotic recombination (Spo11, DMC1, H3K4me3 and PRMD9) are higher in GC-rich TADs. One explanation for these observations is that the occurrence of DSB and recombination in meiotic cells are associated to compositional and epigenetic features (genomic code) that are similar to those guiding the architecture of chromosomes in the interphase nucleus of pre-leptotene spermatocytes.

genomics↗

bioRxiv2018

Topological linkage disequilibrium calculated from coalescent genealogies

We revisit the classical concept of two-locus linkage disequilibrium (LD) and introduce a novel way of looking at haplotypes. In contrast to defining haplotypes as allele combinations at two marker loci, we concentrate on the clustering of sampled chromosomes induced by their coalescent genealogy. The root of a binary coalescent trees defines two clusters of chromosomes. At two different loci this assignment may be different as a result of recombination. We show that the amount of shared chromosomes among clusters at two different loci, measured by the squared correlation, constitutes a natural measure of LD. We call this topological LD (tLD) since it is induced by the topology of the coalescent tree. We find that its rate of decay decreases more slowly with distance between loci than that of conventional LD. Furthermore, tLD has a smaller coefficient of variation, which should render it more accurate for any kind of mapping purposes than conventional LD. We conclude with a practical application to the LCT region in human populations.

evolutionary biology↗