A5016886169- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Prenatal Screening and Diagnostics
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genomics and Rare Diseases
- Renal and related cancers
- Acute Lymphoblastic Leukemia research
- Cancer-related gene regulation
- Dermatological and Skeletal Disorders
- Genetics and Neurodevelopmental Disorders
- Acute Myeloid Leukemia Research
- Hypertrophic osteoarthropathy and related conditions
- Telomeres, Telomerase, and Senescence
- Pregnancy and preeclampsia studies
- Advanced biosensing and bioanalysis techniques
- Congenital heart defects research
- Sexual Differentiation and Disorders
- Genetic and rare skin diseases.
- Kruppel-like factors research
- Gestational Trophoblastic Disease Studies
- Pluripotent Stem Cells Research
- RNA Research and Splicing
National Center For Child Health and Development
2016-2025
National Institute for Japanese Language and Linguistics
2024
National Institutes of Health
2014-2020
Yale University
2020
Rockefeller University
2020
Harvard University
2020
Society for Maternal-Fetal Medicine
2016-2019
Fukuoka University
2008-2014
Sysmex (Japan)
2013
Central Research Laboratories (United Kingdom)
2013
Genome-wide dynamic changes in DNA methylation are indispensable for germline development and genomic imprinting mammals. Here, we report single-base resolution methylome transcriptome maps of mouse germ cells, generated using whole-genome shotgun bisulfite sequencing cDNA (mRNA-seq). Oocyte genomes showed a significant positive correlation between mRNA transcript levels the transcribed region. Sperm had nearly complete coverage methylation, except CpG-rich regions, negative gene expression...
Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression Shh requirement for generating extra digits. Here we identify translocation breakpoint PPD patient and transgenic insertion site the mutant sasquatch ( Ssq ). The genetic lesions both lie within same respective intron LMBR1 / Lmbr1 gene, which resides ≈1 Mb away from . Genetic analysis reveals gene incidental to phenotype mutation directly interrupts...
Differential methylation between the two alleles of a gene has been observed in imprinted regions, where one allele occurs on parent-of-origin basis, inactive X-chromosome females, and at those loci whose is driven by genetic variants. We have extensively characterized substantial range normal human tissues, reciprocal genome-wide uniparental disomies, hydatidiform moles, using combination whole-genome bisulfite sequencing high-density microarrays. This approach allowed us to define profiles...
Whole-genome and -exome resequencing using next-generation sequencers is a powerful approach for identifying genomic variations that are associated with diseases. However, systematic strategies prioritizing causative variants from many candidates to explain the disease phenotype still far being established, because population-specific frequency spectrum of genetic variation has not been characterized. Here, we have collected exomic 1208 Japanese individuals through collaborative effort,...
Fusion genes involving ZNF384 have recently been identified in B-cell precursor acute lymphoblastic leukemia, and 7 fusion partners reported. We further characterized this type of gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we BMP2K as a novel partner for ZNF384. Including the EP300-ZNF384 that recently, total frequency ZNF384-related was 4.1% 291 leukemia patients enrolled single clinical trial, TCF3-ZNF384 most...
DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, segmental duplications were integrated at level with medical genetic data, including 440 rearrangement breakpoints associated disease. This approach enabled discovery candidate genes for developmental diseases autism.
Thousands of regions in gametes have opposing methylation profiles that are largely resolved during the post-fertilization epigenetic reprogramming. However some specific sequences associated with imprinted loci survive this demethylation process. Here we present data describing fate germline-derived humans. With exception a few known paternally methylated germline differentially (DMRs) domains, demonstrate sperm-derived is reprogrammed by blastocyst stage development. In contrast large...
Familial recurrent hydatidiform mole (RHM) is a maternal-effect autosomal recessive disorder usually associated with mutations of the NLRP7 gene. It characterized by HM excessive trophoblastic proliferation, which mimics appearance androgenetic molar conceptuses despite their diploid biparental constitution. has been proposed that phenotypes both types are aberrant genomic imprinting. However no systematic analyses for imprinting defects have reported. Here, we present genome-wide...
The zona fasciculata (zF) in the adrenal cortex contributes to multiple physiological actions through glucocorticoid synthesis. size, proliferation, and synthesis characteristics are all female biased, sexual dimorphism is established by androgen. In this study, transcriptomes were obtained unveil sex differentiation mechanism. Interestingly, both amount of mRNA expressions nearly genes higher females. expression Nr5a1, which essential for steroidogenic cell differentiation, was also biased....
Abstract Insufficient thyroid hormone production in newborns is referred to as congenital hypothyroidism. Multinodular goiter (MNG), characterized by an enlarged gland with multiple nodules, usually seen adults and recognized a separate disorder from Here we performed linkage analysis of family both nongoitrous hypothyroidism MNG identified signal at 15q26.1. Follow-up analyses whole-genome sequencing genetic screening cohorts showed that changes noncoding TTTG microsatellite on 15q26.1 were...
DNA methylation plays a crucial role in mammalian development. While methylome changes acquired the parental genomes are believed to be erased by epigenetic reprogramming, accumulating evidence suggests that sperm caused environmental factors involved disease phenotypes of offspring. These findings imply transferred embryo after reprogramming. However, our understanding this process remains incomplete. Our previous study showed arsenic exposure F0 pregnant mice paternally increased tumor...
5-Bromodeoxyuridine was found to induce flat and enlarged cell shape, characteristics of senescent cells, senescence-associated beta-galactosidase in mammalian cells regardless type or species. In immortal human fibronectin, collagenase I, p21(wafl/sdi-1) mRNAs were immediately very strongly induced, the mortality marker mortalin changed mortal from type. Human lines lacking functional p21(wafl/sdi-1), p16(ink4a), p53 behaved similarly. The protein levels p16(ink4a) did not change uniformly,...
Endothelial nitric-oxide synthase (eNOS) mRNA levels are abnormal in diseases of the cardiovascular system, but changes gene expression cannot be accounted for by transcription alone. We found evidence existence an antisense (sONE) that is derived from a unit (NOS3AS) on opposite DNA strand which human eNOS (NOS3) transcribed at chromosome 7q36. The genes oriented tail-to-tail configuration, and mRNAs encoding sONE complementary 662 nucleotides. could detected variety cell types, both vivo...
Mono-allelic expression of imprinted genes from either the paternal or maternal allele is mediated by imprinting control regions (ICRs), which are epigenetically marked in an allele-specific fashion. Although, somatic cells, these epigenetic marks comprise both DNA methylation and histone methylation, relationship between two modifications imprint acquisition maintenance remains unclear. To address this important question, we analyzed at ICRs mid-gestation embryos that were obtained...
The first cell differentiation in the mammalian development separates trophoblast and embryonic lineages, resulting formation of trophectoderm (TE) inner mass (ICM) blastocysts. Although a lower level global DNA methylation genome TE compared with ICM has been suggested, dynamics profile during TE/ICM not elucidated. To address this issue, we identified tissue-dependent differentially methylated regions (T-DMRs) between stem (TS) (ES) cells. Most these TS–ES T-DMRs were also tissues day (E)...
Fusion genes involving MEF2D have recently been identified in precursor B-cell acute lymphoblastic leukemia, mutually exclusive of the common risk stratifying genetic abnormalities, although their true incidence and associated clinical characteristics remain unknown. We 16 cases leukemia 1 lymphoma harboring fusions, including MEF2D-BCL9 (n=10), MEF2D-HNRNPUL1 (n=6), one novel MEF2D-HNRNPH1 fusion. The fusions overall was 2.4% among consecutive patients enrolled onto a single trial. They...