Prdm9 deficiency of rat oocytes causes synapsis among non-homologous chromosomes and aneuploidy.

Aneuploidy (abnormal chromosome number) accompanies reduced ovarian function in humans and mice, but the reasons behind this concomitance remain underexplored. Some variants in the human gene encoding histone-3-lysine-4,36-trimethyltransferase PRDM9 are associated with aneuploidy, and other variants with ovarian function reduced by premature ovarian failure (POF), but no link between POF and aneuploidy has been revealed. SHR/OlaIpcv rat females lacking PRDM9 manifest POF-a reduced follicle number, litter size, and reproductive age.

Rat PRDM9 shapes recombination landscapes, duration of meiosis, gametogenesis, and age of fertility.

Background: Vertebrate meiotic recombination events are concentrated in regions (hotspots) that display open chromatin marks, such as trimethylation of lysines 4 and 36 of histone 3 (H3K4me3 and H3K36me3). Mouse and human PRDM9 proteins catalyze H3K4me3 and H3K36me3 and determine hotspot positions, whereas other vertebrates lacking PRDM9 recombine in regions with chromatin already opened for another function, such as gene promoters. While these other vertebrate species lacking PRDM9 remain fertile, inactivation of the mouse Prdm9 gene, which shifts the hotspots to the functional regions (including promoters), typically causes gross fertility reduction; and the reasons for these species differences are not clear.

Bardet-Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self-tolerance.

Bardet-Biedl Syndrome (BBS) is a pleiotropic genetic disease caused by the dysfunction of primary cilia. The immune system of patients with ciliopathies has not been investigated. However, there are multiple indications that the impairment of the processes typically associated with cilia may have influence on the hematopoietic compartment and immunity.

Meiotic epigenetic factor PRDM9 impacts sperm quality of hybrid mice.

Reduced fertility of male mouse hybrids relative to their parents, or hybrid sterility, is governed by the hybrid sterility 1 (Hst1) locus. Rescue experiments with transgenes carrying sequences within or near Hst1 manifested that Hst1 contains the gene encoding meiosis-specific histone methyltransferase PRDM9. The Prdm9 gene is responsible for partial meiotic arrest, testicular atrophy, and low sperm count in (C57BL/6J x PWD)F1 mouse hybrids.

Copy-number variation introduced by long transgenes compromises mouse male fertility independently of pachytene checkpoints.

Long transgenes are often used in mammalian genetics, e.g., to rescue mutations in large genes.

Histone methyltransferase PRDM9 is not essential for meiosis in male mice.

A hallmark of meiosis is the rearrangement of parental alleles to ensure genetic diversity in the gametes. These chromosome rearrangements are mediated by the repair of programmed DNA double-strand breaks (DSBs) as genetic crossovers between parental homologs. In mice, humans, and many other mammals, meiotic DSBs occur primarily at hotspots, determined by sequence-specific binding of the PRDM9 protein.

A Mutation of the Prdm9 Mouse Hybrid Sterility Gene Carried by a Transgene.

PRDM9 is a protein with histone-3-methyltransferase activity, which specifies the sites of meiotic recombination in mammals. Deficiency of the Prdm9 gene in the laboratory mouse results in complete arrest of the meiotic prophase of both sexes. Moreover, the combination of certain PRDM9 alleles from different mouse subspecies causes hybrid sterility, e.

Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.

Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm) and Mus m.

Prdm9 incompatibility controls oligospermia and delayed fertility but no selfish transmission in mouse intersubspecific hybrids.

PR-domain 9 (Prdm9) is the first hybrid sterility gene identified in mammals. The incompatibility between Prdm9 from Mus musculus domesticus (Mmd; the B6 strain) and the Hstx2 region of chromosome (Chr) X from M. m.

Interallelic and intergenic incompatibilities of the Prdm9 (Hst1) gene in mouse hybrid sterility.

The Dobzhansky-Muller model of incompatibilities explains reproductive isolation between species by incorrect epistatic interactions. Although the mechanisms of speciation are of great interest, no incompatibility has been characterized at the gene level in mammals. The Hybrid sterility 1 gene (Hst1) participates in the arrest of meiosis in F(1) males of certain strains from two Mus musculus subspecies, e.

A mouse speciation gene encodes a meiotic histone H3 methyltransferase.

Speciation genes restrict gene flow between the incipient species and related taxa. Three decades ago, we mapped a mammalian speciation gene, hybrid sterility 1 (Hst1), in the intersubspecific hybrids of house mouse. Here, we identify this gene as Prdm9, encoding a histone H3 lysine 4 trimethyltransferase.

Mouse consomic strains: exploiting genetic divergence between Mus m. musculus and Mus m. domesticus subspecies.

Consomic (chromosome substitution) strains (CSs) represent the most recent addition to the mouse genetic resources aimed to genetically analyze complex trait loci (QTLs). In this study, we report the development of a set of 28 mouse intersubspecific CSs. In each CS, we replaced a single chromosome of the C57BL/6J (B6) inbred strain (mostly Mus m.

Fine haplotype structure of a chromosome 17 region in the laboratory and wild mouse.

Extensive linkage disequilibrium among classical laboratory strains represents an obstacle in the high-resolution haplotype mapping of mouse quantitative trait loci (QTL). To determine the potential of wild-derived mouse strains for fine QTL mapping, we constructed a haplotype map of a 250-kb region of the t-complex on chromosome 17 containing the Hybrid sterility 1 (Hst1) gene. We resequenced 33 loci from up to 80 chromosomes of five mouse (sub)species.

Conserved alternative and antisense transcripts at the programmed cell death 2 locus.

Background: The programmed cell death 2 (Pdcd2) gene on mouse chromosome 17 was evaluated as a member of a highly conserved synteny, a candidate for an imprinted locus, and a candidate for the Hybrid sterility 1 (Hst1) gene.

Results: New mouse transcripts were identified at this locus: an alternative Pdcd2 mRNA skipping the last two coding exons and two classes of antisense RNAs. One class of the antisense RNA overlaps the alternative exon and the other the entire Pdcd2 gene.

Comparative analysis of the PDCD2-TBP-PSMB1 region in vertebrates.

Three orthologous genes encoding programmed cell death 2 (PDCD2), TATA-binding protein (TBP), and proteasomal subunit C5 (PSMB1) proteins have been shown previously to be nonrandomly distributed in both mammalian and invertebrate genomes. Here we analyze a conserved synteny of the PDCD2, TBP, and PSMB1 orthologs in four nonmammalian vertebrates. Homologous genes of the chicken, zebrafish, fugu, and Tetraodon nigroviridis were identified.

Eukaryotic operon genes can define highly conserved syntenies.

The synteny conservation of the members of eukaryotic operons was investigated by mapping their orthologues in Drosophila, human, and other eukaryotes. While the homologues of the operon members are generally not linked, some examples of highly conserved syntenies were found. The most significant synteny involves two members of one C.

Synteny of orthologous genes conserved in mammals, snake, fly, nematode, and fission yeast.

Four mouse genes, programmed cell death 2 (Pdcd2 or Rp8), brain protein 44-like (Brp441), bystin-like (Bysl), and uncoordinated-93-like (Unc931) genes were mapped to Chromosome (Chr) 17. The orthologs of these and other mouse Chr 17 genes are localized on Chr III of Caenorhabditis elegans, thus defining a syntenic group conserved between vertebrates and nonvertebrates. In human, mouse, and snake, the PDCD2-, and TATA-binding protein (TBP)-encoding genes are adjacent tail-to-tail.

Transcription and RNA processing of mammalian genes in Saccharomyces cerevisiae.

The recognition of mammalian genes encoded within a mouse yeast artificial chromosome (YAC) by the yeast transcription and RNA processing machinery was investigated. Transcripts from five genes known to be encoded by the YAC were all found in the total yeast RNA. Of 12 mouse introns assayed, six were correctly spliced by the yeast.

Linkage of TATA-binding protein and proteasome subunit C5 genes in mice and humans reveals synteny conserved between mammals and invertebrates.

The TATA-binding protein (TBP) is a factor required for the transcription of all classes of eukaryotic genes. Here, we demonstrate that in the mouse the TBP-encoding gene (Tbp) resides next to the proteasomal subunit C5-encoding gene (Psmb1). The genes are located on mouse chromosome 17 in the t complex within the Hybrid sterility 1 (Hst1) region.

Isolation of candidate hybrid sterility 1 genes by cDNA selection in a 1.1 megabase pair region on mouse chromosome 17.

The Hybrid sterility 1 (Hst1) gene causes male infertility in crosses between certain inbred strains of the laboratory and wild mouse, Mus musculus. To identify the causative gene, we have searched YAC clones encompassing the Hst1 region for testis-expressed sequences, using the cDNA selection method. We isolated 12 non-overlapping cDNA clones, sequenced them, and placed them on a physical map based on the analysis of YAC clones and total genomic DNA.