Biomedical subjects

Takehiko Itoh

Publications and source records attributed to Takehiko Itoh.

11 recordsLinked to original sources

PubMed2026

A-liner: linear alignment visualizer for genome comparisons.

SUMMARY: A-liner is a flexible command-line tool for linear visualization of genome-scale sequence alignments, supporting outputs from multiple aligners and integrated visualization of annotations, highlights, quantitative tracks, and coordinate scales. It is applicable to a wide range of organisms, from bacteria to large eukaryotic genomes, and facilitates efficient generation of publication-ready comparative genome visualizations. AVAILABILITY AND IMPLEMENTATION: The source code and example output files for a-liner are available in the GitHub repository: https://github.com/mokuno3430/a-liner. A-liner v1.1.0 has been archived on Zenodo at https://doi.org/10.5281/zenodo.19702001.

Software↗

PubMed2025

Where Did the Y Chromosome in the Spiny Rat Go, and How Did It Get There?

The XX/XY sex chromosome system is highly conserved across mammals, with rare exceptions where males lack a Y chromosome. Among these is the genus Tokudaia, a group of spiny rats comprising three species with unique sex chromosome systems deviating from the typical XX/XY pattern. While Tokudaia osimensis and Tokudaia tokunoshimensis have completely lost the Y chromosome, they retain some Y-linked genes on the X chromosome. In contrast, Tokudaia muenninki retains large sex chromosomes where both the X and Y chromosomes have fused with an autosome pair, carrying multi-copied Y-linked genes, including Sry. In this study, we generated chromosome-level genome assemblies for male individuals of all three Tokudaia species. By investigating loci typically associated with rodent Y-linked genes, we characterized sequences derived from the Tokudaia Y-chromosomal most recent common ancestor (Tokudaia Y-MRCA) and traced their evolutionary trajectories. Our analyses revealed that an initial X-to-Y translocation of a sequence containing the boundary-associated segmental duplication in a common ancestor of Tokudaia marked the beginning of their unique sex chromosome evolution. The boundary-associated segmental duplication, uniquely multi-copied in Tokudaia, facilitated further rearrangements through nonallelic homologous recombination and duplications. These processes culminated in subsequent Y-to-X translocations and duplications, leading to the complete loss of the Y chromosome as a distinct entity while preserving Y-linked genes in a multicopy state on the X chromosome. These findings highlight Tokudaia's rapid sex chromosome evolution within 3 million years and provide insights into the mechanisms underlying Y chromosome loss, contributing to a broader understanding of sex chromosome evolution in rodents.

Animals↗

PubMed2006

Meiotic cohesins modulate chromosome compaction during meiotic prophase in fission yeast.

The meiotic cohesin Rec8 is required for the stepwise segregation of chromosomes during the two rounds of meiotic division. By directly measuring chromosome compaction in living cells of the fission yeast Schizosaccharomyces pombe, we found an additional role for the meiotic cohesin in the compaction of chromosomes during meiotic prophase. In the absence of Rec8, chromosomes were decompacted relative to those of wild-type cells. Conversely, loss of the cohesin-associated protein Pds5 resulted in hypercompaction. Although this hypercompaction requires Rec8, binding of Rec8 to chromatin was reduced in the absence of Pds5, indicating that Pds5 promotes chromosome association of Rec8. To explain these observations, we propose that meiotic prophase chromosomes are organized as chromatin loops emanating from a Rec8-containing axis: the absence of Rec8 disrupts the axis, resulting in disorganized chromosomes, whereas reduced Rec8 loading results in a longitudinally compacted axis with fewer attachment points and longer chromatin loops.

Cell Cycle Proteins↗

PubMed2006

Chromosomal association of the Smc5/6 complex reveals that it functions in differently regulated pathways.

The SMC protein complexes safeguard genomic integrity through their functions in chromosome segregation and repair. The chromosomal localization of the budding yeast Smc5/6 complex determined here reveals that the complex works specifically on the duplicated genome in differently regulated pathways. The first controls the association to centromeres and chromosome arms in unchallenged cells, the second regulates the association to DNA breaks, and the third directs the complex to the chromosome arm that harbors the ribosomal DNA arrays. The chromosomal interaction pattern predicts a function that becomes more important with increasing chromosome length and that the complex's role in unchallenged cells is independent of DNA damage. Additionally, localization of Smc6 to collapsed replication forks indicates an involvement in their rescue. Altogether this shows that the complex maintains genomic integrity in multiple ways, and evidence is presented that the Smc5/6 complex is needed during replication to prevent the accumulation of branched chromosome structures.

Cell Cycle Proteins↗

PubMed2006

Human chromosome 11 DNA sequence and analysis including novel gene identification.

Chromosome 11, although average in size, is one of the most gene- and disease-rich chromosomes in the human genome. Initial gene annotation indicates an average gene density of 11.6 genes per megabase, including 1,524 protein-coding genes, some of which were identified using novel methods, and 765 pseudogenes. One-quarter of the protein-coding genes shows overlap with other genes. Of the 856 olfactory receptor genes in the human genome, more than 40% are located in 28 single- and multi-gene clusters along this chromosome. Out of the 171 disorders currently attributed to the chromosome, 86 remain for which the underlying molecular basis is not yet known, including several mendelian traits, cancer and susceptibility loci. The high-quality data presented here--nearly 134.5 million base pairs representing 99.8% coverage of the euchromatic sequence--provide scientists with a solid foundation for understanding the genetic basis of these disorders and other biological phenomena.

Chromosomes, Human, Pair 11↗

PubMed2006

Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I.

Segregation of homologous maternal and paternal centromeres to opposite poles during meiosis I depends on post-replicative crossing over between homologous non-sister chromatids, which creates chiasmata and therefore bivalent chromosomes. Destruction of sister chromatid cohesion along chromosome arms due to proteolytic cleavage of cohesin's Rec8 subunit by separase resolves chiasmata and thereby triggers the first meiotic division. This produces univalent chromosomes, the chromatids of which are held together by centromeric cohesin that has been protected from separase by shugoshin (Sgo1/MEI-S332) proteins. Here we show in both fission and budding yeast that Sgo1 recruits to centromeres a specific form of protein phosphatase 2A (PP2A). Its inactivation causes loss of centromeric cohesin at anaphase I and random segregation of sister centromeres at the second meiotic division. Artificial recruitment of PP2A to chromosome arms prevents Rec8 phosphorylation and hinders resolution of chiasmata. Our data are consistent with the notion that efficient cleavage of Rec8 requires phosphorylation of cohesin and that this is blocked by PP2A at meiosis I centromeres.

Animals↗

PubMed2006

Comparative analysis of chimpanzee and human Y chromosomes unveils complex evolutionary pathway.

The mammalian Y chromosome has unique characteristics compared with the autosomes or X chromosomes. Here we report the finished sequence of the chimpanzee Y chromosome (PTRY), including 271 kb of the Y-specific pseudoautosomal region 1 and 12.7 Mb of the male-specific region of the Y chromosome. Greater sequence divergence between the human Y chromosome (HSAY) and PTRY (1.78%) than between their respective whole genomes (1.23%) confirmed the accelerated evolutionary rate of the Y chromosome. Each of the 19 PTRY protein-coding genes analyzed had at least one nonsynonymous substitution, and 11 genes had higher nonsynonymous substitution rates than synonymous ones, suggesting relaxation of selective constraint, positive selection or both. We also identified lineage-specific changes, including deletion of a 200-kb fragment from the pericentromeric region of HSAY, expansion of young Alu families in HSAY and accumulation of young L1 elements and long terminal repeat retrotransposons in PTRY. Reconstruction of the common ancestral Y chromosome reflects the dynamic changes in our genomes in the 5-6 million years since speciation.

Animals↗

PubMed2005

Identification of large ancient duplications associated with human gene deserts.

We identified 15 regions of >1 Mb in the human genome composed of large ancient local duplications corresponding to gene deserts. We detected these intrachromosomal duplications in mouse and dog but not in chicken; they present as patches of similarity as low as 60%. These findings suggest that some human gene deserts originated from duplications of segments lacking genes in a mammalian common ancestor.

Animals↗

PubMed2005

DNA sequence and analysis of human chromosome 18.

Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements.

Aneuploidy↗

PubMed2004

Cohesin relocation from sites of chromosomal loading to places of convergent transcription.

Sister chromatids, the products of eukaryotic DNA replication, are held together by the chromosomal cohesin complex after their synthesis. This allows the spindle in mitosis to recognize pairs of replication products for segregation into opposite directions. Cohesin forms large protein rings that may bind DNA strands by encircling them, but the characterization of cohesin binding to chromosomes in vivo has remained vague. We have performed high resolution analysis of cohesin association along budding yeast chromosomes III-VI. Cohesin localizes almost exclusively between genes that are transcribed in converging directions. We find that active transcription positions cohesin at these sites, not the underlying DNA sequence. Cohesin is initially loaded onto chromosomes at separate places, marked by the Scc2/Scc4 cohesin loading complex, from where it appears to slide to its more permanent locations. But even after sister chromatid cohesion is established, changes in transcription lead to repositioning of cohesin. Thus the sites of cohesin binding and therefore probably sister chromatid cohesion, a key architectural feature of mitotic chromosomes, display surprising flexibility. Cohesin localization to places of convergent transcription is conserved in fission yeast, suggesting that it is a common feature of eukaryotic chromosomes.

Cell Cycle Proteins↗

PubMed2002

Construction and analysis of a human-chimpanzee comparative clone map.

The recently released human genome sequences provide us with reference data to conduct comparative genomic research on primates, which will be important to understand what genetic information makes us human. Here we present a first-generation human-chimpanzee comparative genome map and its initial analysis. The map was constructed through paired alignment of 77,461 chimpanzee bacterial artificial chromosome end sequences with publicly available human genome sequences. We detected candidate positions, including two clusters on human chromosome 21 that suggest large, nonrandom regions of difference between the two genomes.

Animals↗