A5023502395- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Genetic Mapping and Diversity in Plants and Animals
- CRISPR and Genetic Engineering
- Liver physiology and pathology
- Chromosomal and Genetic Variations
- Organ Transplantation Techniques and Outcomes
- Genomic variations and chromosomal abnormalities
- Photosynthetic Processes and Mechanisms
- RNA modifications and cancer
- Pancreatic function and diabetes
- RNA and protein synthesis mechanisms
- Molecular Biology Techniques and Applications
- Meat and Animal Product Quality
- Genetic and phenotypic traits in livestock
- Mitochondrial Function and Pathology
- Genetic diversity and population structure
- Fungal Biology and Applications
- Bioinformatics and Genomic Networks
- Genetics and Neurodevelopmental Disorders
- Pediatric Hepatobiliary Diseases and Treatments
- Genetic Syndromes and Imprinting
- Diatoms and Algae Research
- Fungal and yeast genetics research
Jackson Laboratory
2014-2023
Sofia University "St. Kliment Ohridski"
1986-2023
Centre for Human Genetics
2007
University of Oxford
2007
University of Tennessee Health Science Center
2007
Albert Einstein College of Medicine
2000-2004
University of Cagliari
1999
Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, controls activation recombination multiple distant has been mapped within a 181-kilobase interval, three whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis...
Rare gene knockouts in adult humans On average, most people's genomes contain approximately 100 completely nonfunctional genes. These loss-of-function (LOF) mutations tend to be rare and/or occur only as a single copy within individuals. Narasimhan et al. investigated LOF Pakistani population with high levels of consanguinity. Examining alleles that were identical by descent, they found, expected, an absence homozygote for certain protein-coding However, also identified many no apparent...
Genotyping microarrays are an important resource for genetic mapping, population genetics, and monitoring of the integrity laboratory stocks. We have developed third generation Mouse Universal Array (MUGA) series, GigaMUGA, a 143,259-probe Illumina Infinium II array house mouse (Mus musculus). The bulk content GigaMUGA is optimized mapping in Collaborative Cross Diversity Outbred populations, substrain-level identification mice. In addition to 141,090 single nucleotide polymorphism probes,...
In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs first step in meiotic recombination by specifying locations of hotspots, sites genetic recombination. binds to DNA at hotspots through its domain activates trimethylating H3K4 on adjacent nucleosomes PR/SET domain. Recently, isolated was shown capable also H3K36 vitro, raising question whether this reaction occurs vivo during meiosis, if so, what function might be. Here, we show that...
A set of 1638 informative SNP markers easily assayed by the Amplifluor genotyping system were tested in 102 mouse strains, including majority common and wild-derived inbred strains available from The Jackson Laboratory. Selected publicly databases, are on average ∼1.5 Mb apart and, whenever possible, represent rare allele at least two strains. assays developed for each marker performed independent DNA samples strain. mean number polymorphisms between was 608±136 SD. Several tests indicate...
Among mammals, genetic recombination occurs at highly delimited sites known as hotspots. They are typically 1-2 kb long and vary much a 1,000-fold or more in activity. Although is about the molecular details of process itself, factors determining location relative activity hotspots poorly understood. To further our understanding, we have collected mapped locations 5,472 crossover events along mouse Chromosome 1 arising 6,028 meioses male female reciprocal F1 hybrids C57BL/6J CAST/EiJ mice....
In mammals, genetic recombination during meiosis is limited to a set of 1- 2-kb regions termed hotspots. Their locations are predominantly determined by the zinc finger protein PRDM9, which binds DNA in hotspots and subsequently uses its SET domain locally trimethylate histone H3 at lysine 4 (H3K4me3). This sets stage for double-strand break (DSB) formation reciprocal exchange between chromatids, forming Holliday junctions. Here we report genome-wide analyses PRDM9-dependent modifications...
Meiotic recombination generates new genetic variation and assures the proper segregation of chromosomes in gametes. PRDM9, a zinc finger protein with histone methyltransferase activity, initiates meiotic by binding DNA at hotspots directing position double-strand breaks (DSB). The DSB repair mechanism suggests that should eventually self-destruct, yet genome-wide levels remain constant, conundrum known as hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we measured...
In mammals, meiotic recombination occurs at 1- to 2-kb genomic regions termed hotspots, whose positions and activities are determined by PRDM9, a DNA-binding histone methyltransferase. We show that the KRAB domain of PRDM9 forms complexes with additional proteins allow hotspots proceed into next phase recombination. By combination yeast-two hybrid assay, in vitro binding, coimmunoprecipitation from mouse spermatocytes, we identified four directly interact PRDM9’s domain, namely CXXC1, EWSR1,...
Significant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported multiple crosses, including the Collaborative Cross (CC). Among eight CC founder inbred strains, we found that Chr was exclusive to females were heterozygous for WSB/EiJ allele within a 9.3 Mb region (Chr 76.9 - 86.2 Mb). A copy number gain of 127 kb-long DNA...
Genetic recombination plays an important role in evolution, facilitating the creation of new, favorable combinations alleles and removal deleterious mutations by unlinking them from surrounding sequences. In most mammals, placement genetic crossovers is determined binding PRDM9, a highly polymorphic protein with long zinc finger array, to its cognate sites. It one over 800 genes encoding proteins domains human genome. We report novel technique, Affinity-seq, that for first time identifies...
Abstract Background Meiotic recombination ensures proper segregation of homologous chromosomes and creates genetic variation. In many organisms, occurs at limited sites, termed 'hotspots', whose positions in mammals are determined by PR domain member 9 (PRDM9), a long-array zinc-finger chromatin-modifier protein. Determining the rules governing DNA binding PRDM9 is major issue understanding how it functions. Results Mouse protein variants bind to hotspot sequences manner that specific for...
Evidence from inbred strains of mice indicates that a quarter or more the mammalian genome consists chromosome regions containing clusters functionally related genes. The intense selection pressures during inbreeding favor coinheritance optimal sets alleles among these genetically linked, genes, resulting in extensive domains linkage disequilibrium (LD) set 60 diverse strains. Recombination disrupts preferred combinations reduces ability offspring to survive further inbreeding. LD is also...
Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation chromatids. Mammalian events are concentrated at specialized sites, termed hotspots, whose locations determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set hotspots. In populations exhibiting high frequencies heterozygosity, questions remain about...
Recently, we reported near-complete repopulation of the rat liver by transplanted hepatocytes using retrorsine (RS), a pyrrolizidine alkaloid that alkylates cellular DNA and blocks proliferation resident hepatocytes, followed transplantation normal in conjunction with two-thirds partial hepatectomy (PH). Because PH is not feasible for use humans, present study, evaluated ability thyroid hormone (triiodothyronine [T 3 ]), known hepatic mitogen, to stimulate model. T initiates morphogenesis...
A hallmark of meiosis is the rearrangement parental alleles to ensure genetic diversity in gametes. These chromosome rearrangements are mediated by repair programmed DNA double-strand breaks (DSBs) as crossovers between homologs. In mice, humans, and many other mammals, meiotic DSBs occur primarily at hotspots, determined sequence-specific binding PRDM9 protein. Without PRDM9, near gene promoters functional sites. Studies a limited number mouse strains showed that required complete meiosis,...
The human genome contains about 800 C2H2 zinc finger proteins (ZFPs), and most of them are composed long arrays fingers. Standard ZFP recognition model asserts longer should recognize DNA-binding sites. However, recent experimental efforts to identify in vivo binding sites contradict this assumption, with many exhibiting short motifs. Here we use ZFY, CTCF, ZIM3, ZNF343 as examples address three closely related questions: What the reasons that impede current motif discovery methods?...