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Frontiers in Cell and Developmental... 2023During the pachytene stage in mammalian meiosis, the X and Y chromosomes remain largely unsynapsed outside the pseudoautosomal region, while autosomes are fully... (Review)
Review
During the pachytene stage in mammalian meiosis, the X and Y chromosomes remain largely unsynapsed outside the pseudoautosomal region, while autosomes are fully synapsed. Then, the sex chromosomes are compartmentalized into a "sex body" in the nucleus and are subjected to meiotic sex chromosome inactivation (MSCI). For decades, the formation and functioning of the sex body and MSCI have been subjects worth exploring. Notably, a series of proteins have been reported to be located on the sex body area and inferred to play an essential role in MSCI; however, the proteins that are actually located in this area and how these proteins promote sex body formation and establish MSCI remain unclear. Collectively, the DNA damage response factors, downstream fanconi anemia proteins, and other canonical repressive histone modifications have been reported to be associated with the sex body. Here, this study reviews the factors located on the sex body area and tries to provide new insights into studying this mysterious domain.
PubMed: 37123420
DOI: 10.3389/fcell.2023.1165745 -
Annals of Anatomy = Anatomischer... Nov 2021This year marks the twentieth anniversary of the publication of the first draft of the human genome and its broad availability to the scientific community. In parallel,... (Review)
Review
This year marks the twentieth anniversary of the publication of the first draft of the human genome and its broad availability to the scientific community. In parallel, the annotation of the mouse genome led to the identification and analysis of countless genes by means of genetic manipulation. Today, when comparing both genomes, it might surprise that some genes are still seeking their respective homologs in either species. In this review, we aim at raising awareness for the remarkable differences between the researcher's favorite rodents, i.e., mice and rats, when it comes to the generation of rodent research models regarding genes with a particular delicate localization, namely the pseudoautosomal region on both sex chromosomes. Many of these genes are of utmost clinical relevance in humans and still miss a rodent disease model giving their absence in mice and rats or low sequence similarity compared to humans. The abundance of rodents within mammals prompted us to investigate different branches of rodents leading us to the re-discovery of the guinea pig as a mammalian research model for a distinct group of genes.
Topics: Animals; Guinea Pigs; Mammals; Models, Animal; Rats
PubMed: 34000371
DOI: 10.1016/j.aanat.2021.151765 -
Nature Ecology & Evolution Jul 2023The Y chromosome usually plays a critical role in determining male sex and comprises sequence classes that have experienced unique evolutionary trajectories. Here we...
The Y chromosome usually plays a critical role in determining male sex and comprises sequence classes that have experienced unique evolutionary trajectories. Here we generated 19 new primate sex chromosome assemblies, analysed them with 10 existing assemblies and report rapid evolution of the Y chromosome across primates. The pseudoautosomal boundary has shifted at least six times during primate evolution, leading to the formation of a Simiiformes-specific evolutionary stratum and to the independent start of young strata in Catarrhini and Platyrrhini. Different primate lineages experienced different rates of gene loss and structural and chromatin change on their Y chromosomes. Selection on several Y-linked genes has contributed to the evolution of male developmental traits across the primates. Additionally, lineage-specific expansions of ampliconic regions have further increased the diversification of the structure and gene composition of the Y chromosome. Overall, our comprehensive analysis has broadened our knowledge of the evolution of the primate Y chromosome.
Topics: Animals; Male; Evolution, Molecular; Y Chromosome; Primates
PubMed: 37268856
DOI: 10.1038/s41559-022-01974-x -
Cell Reports Aug 2023Meiotic crossovers are required for the faithful segregation of homologous chromosomes and to promote genetic diversity. However, it is unclear how crossover formation...
Meiotic crossovers are required for the faithful segregation of homologous chromosomes and to promote genetic diversity. However, it is unclear how crossover formation is regulated, especially on the XY chromosomes, which show a homolog only at the tiny pseudoautosomal region. Here, we show that ATF7IP2 is a meiosis-specific ortholog of ATF7IP and a partner of SETDB1. In the absence of ATF7IP2, autosomes show increased axis length and more crossovers; however, many XY chromosomes lose the obligatory crossover, although the overall XY axis length is also increased. Additionally, meiotic DNA double-strand break formation/repair may also be affected by altered histone modifications. Ultimately, spermatogenesis is blocked, and male mice are infertile. These findings suggest that ATF7IP2 constraints autosomal axis length and crossovers on autosomes; meanwhile, it also modulates XY chromosomes to establish meiotic sex chromosome inactivation for cell-cycle progression and to ensure XY crossover formation during spermatogenesis.
Topics: Animals; Male; Mice; Chromosome Segregation; Histone-Lysine N-Methyltransferase; Meiosis; Sex Chromosomes; Spermatogenesis; Transcription Factors
PubMed: 37542719
DOI: 10.1016/j.celrep.2023.112953 -
Genes Feb 2023The chicken D blood system is one of 13 alloantigen systems found on chicken red blood cells. Classical recombinant studies located the D blood system on chicken...
The chicken D blood system is one of 13 alloantigen systems found on chicken red blood cells. Classical recombinant studies located the D blood system on chicken chromosome 1, but the candidate gene was unknown. Multiple resources were utilized to identify the chicken D system candidate gene, including genome sequence information from both research and elite egg production lines for which D system alloantigen alleles were reported, and DNA from both pedigree and non-pedigree samples with known D alleles. Genome-wide association analyses using a 600 K or a 54 K SNP chip plus DNA from independent samples identified a strong peak on chicken chromosome 1 at 125-131 Mb (GRCg6a). Cell surface expression and the presence of exonic non-synonymous SNP were used to identify the candidate gene. The chicken CD99 gene showed the co-segregation of SNP-defined haplotypes and serologically defined D blood system alleles. The CD99 protein mediates multiple cellular processes including leukocyte migration, T-cell adhesion, and transmembrane protein transport, affecting peripheral immune responses. The corresponding human gene is found syntenic to the pseudoautosomal region 1 of human X and Y chromosomes. Phylogenetic analyses show that CD99 has a paralog, XG, that arose by duplication in the last common ancestor of the amniotes.
Topics: Animals; Humans; Chickens; Isoantigens; Genome-Wide Association Study; Phylogeny; DNA; Alleles; 12E7 Antigen
PubMed: 36833329
DOI: 10.3390/genes14020402 -
Plant Physiology Sep 2023Sex chromosomes have evolved independently in many different plant lineages. Here, we describe reference genomes for spinach (Spinacia oleracea) X and Y haplotypes by...
Sex chromosomes have evolved independently in many different plant lineages. Here, we describe reference genomes for spinach (Spinacia oleracea) X and Y haplotypes by sequencing homozygous XX females and YY males. The long arm of 185-Mb chromosome 4 carries a 13-Mb X-linked region (XLR) and 24.1-Mb Y-linked region (YLR), of which 10 Mb is Y specific. We describe evidence that this reflects insertions of autosomal sequences creating a "Y duplication region" or "YDR" whose presence probably directly reduces genetic recombination in the immediately flanking regions, although both the X and Y sex-linked regions are within a large pericentromeric region of chromosome 4 that recombines rarely in meiosis of both sexes. Sequence divergence estimates using synonymous sites indicate that YDR genes started diverging from their likely autosomal progenitors about 3 MYA, around the time when the flanking YLR stopped recombining with the XLR. These flanking regions have a higher density of repetitive sequences in the YY than the XX assembly and include slightly more pseudogenes compared with the XLR, and the YLR has lost about 11% of the ancestral genes, suggesting some degeneration. Insertion of a male-determining factor would have caused Y linkage across the entire pericentromeric region, creating physically small, highly recombining, terminal pseudoautosomal regions. These findings provide a broader understanding of the origin of sex chromosomes in spinach.
Topics: Spinacia oleracea; Repetitive Sequences, Nucleic Acid; Sex Chromosomes; Evolution, Molecular
PubMed: 37403642
DOI: 10.1093/plphys/kiad389 -
Proceedings of the National Academy of... Nov 2023Meiotic DNA double-strand breaks (DSBs) initiate homologous recombination and are crucial for ensuring proper chromosome segregation. In mice, ANKRD31 recently emerged...
Meiotic DNA double-strand breaks (DSBs) initiate homologous recombination and are crucial for ensuring proper chromosome segregation. In mice, ANKRD31 recently emerged as a regulator of DSB timing, number, and location, with a particularly important role in targeting DSBs to the pseudoautosomal regions (PARs) of sex chromosomes. ANKRD31 interacts with multiple proteins, including the conserved and essential DSB-promoting factor REC114, so it was hypothesized to be a modular scaffold that "anchors" other proteins together and to meiotic chromosomes. To determine whether and why the REC114 interaction is important for ANKRD31 function, we generated mice with mutations that either reduced (missense mutation) or eliminated (C-terminal truncation) the ANKRD31-REC114 interaction without diminishing contacts with other known partners. A complete lack of the ANKRD31-REC114 interaction mimicked an null, with delayed DSB formation and recombination, defects in DSB repair, and altered DSB locations including failure to target DSBs to the PARs. In contrast, when the ANKRD31-REC114 interaction was substantially but not completely disrupted, spermatocytes again showed delayed DSB formation globally, but recombination and repair were hardly affected and DSB locations were similar to control mice. The missense allele showed a dosage effect, wherein combining it with the null or C-terminal truncation allele resulted in intermediate phenotypes for DSB formation, recombination, and DSB locations. Our results show that ANKRD31 function is critically dependent on its interaction with REC114 and that defects in ANKRD31 activity correlate with the severity of the disruption of the interaction.
Topics: Animals; Male; Mice; Chromosomes; Homologous Recombination; Meiosis; Mutation; Spermatogenesis
PubMed: 37976262
DOI: 10.1073/pnas.2310951120 -
Evolution; International Journal of... Mar 2021The attention given to heteromorphism and genetic degeneration of "classical sex chromosomes" (Y chromosomes in XY systems, and the W in ZW systems that were studied...
The attention given to heteromorphism and genetic degeneration of "classical sex chromosomes" (Y chromosomes in XY systems, and the W in ZW systems that were studied first and are best described) has perhaps created the impression that the absence of recombination between sex chromosomes is inevitable. I here argue that continued recombination is often to be expected, that absence of recombination is surprising and demands further study, and that the involvement of selection in reduced recombination is not yet well understood. Despite a long history of investigations of sex chromosome pairs, there is a need for more quantitative approaches to studying sex-linked regions. I describe a scheme to help understand the relationships between different properties of sex-linked regions. Specifically, I focus on their sizes (differentiating between small regions and extensive fully sex-linked ones), the times when they evolved, and their differentiation, and review studies using DNA sequencing in nonmodel organisms that are providing information about the processes causing these properties.
Topics: Animals; Chromosomes, Plant; Evolution, Molecular; Female; Male; Phylogeny; Plants; Recombination, Genetic; Sequence Analysis, DNA; Sex Chromosomes
PubMed: 33592115
DOI: 10.1111/evo.14196 -
European Journal of Medical Genetics Jul 2021Ring X is a chromosomal anomaly mainly seen in females with turner syndrome and usually present in mosaic form with 45,X cells (45,X/46,X,r(X)) because of their mitotic...
Ring X is a chromosomal anomaly mainly seen in females with turner syndrome and usually present in mosaic form with 45,X cells (45,X/46,X,r(X)) because of their mitotic instability. In males it is an extremely rare finding because large nullisomy for X chromosome material is likely not compatible with survival. Only two cases of male with ring chromosome X were previously reported. We report here a four-year-old male with ring chromosome X characterized using Karyotype, FISH and array CGH and presenting short stature, microcephaly and hypospadias. Molecular investigations showed 923 Kb terminal deletion on the pseudoautosomal region 1 (PAR1) including SHOX gene followed by a duplication of 2.4 Mb. The absence of functional nullisomy because of a second copy of deleted genes was present in chromosome Y PAR1 region may explain the compatibility with survival in our case of male with ring X. Short stature common with the two previously reported cases is likely related to SHOX gene deletion but also to the effect of "ring syndrome". However, hypospadias was not reported in the previous cases and can be due to the associated duplication outside PAR1 region including in particular PRKX gene coding for a protein involved in urogenital system morphogenesis.
Topics: Child, Preschool; Chromosome Disorders; Chromosomes, Human, X; Gene Deletion; Gene Duplication; Humans; Hypospadias; Male; Microcephaly; Ring Chromosomes; Short Stature Homeobox Protein; Syndrome
PubMed: 33872775
DOI: 10.1016/j.ejmg.2021.104225 -
Molecular Syndromology Apr 2016SHOX in the short arm pseudoautosomal region (PAR1) of sex chromosomes is one of the major growth genes in humans. SHOX haploinsufficiency results in idiopathic short... (Review)
Review
SHOX in the short arm pseudoautosomal region (PAR1) of sex chromosomes is one of the major growth genes in humans. SHOX haploinsufficiency results in idiopathic short stature and Léri-Weill dyschondrosteosis and is associated with the short stature of patients with Turner syndrome. The SHOX protein likely controls chondrocyte apoptosis by regulating multiple target genes including BNP,Fgfr3, Agc1, and Ctgf. SHOX haploinsufficiency frequently results from deletions and duplications in PAR1 involving SHOX exons and/or the cis-acting enhancers, while exonic point mutations account for a small percentage of cases. The clinical severity of SHOX haploinsufficiency reflects hormonal conditions rather than mutation types. Growth hormone treatment seems to be beneficial for cases with SHOX haploinsufficiency, although the long-term outcomes of this therapy require confirmation. Future challenges in SHOX research include elucidating its precise function in the developing limbs, identifying additional cis-acting enhancers, and determining optimal therapeutic strategies for patients.
PubMed: 27194967
DOI: 10.1159/000444596