A5050554474- Genetic Associations and Epidemiology
- Cancer Genomics and Diagnostics
- Evolution and Genetic Dynamics
- Pancreatic and Hepatic Oncology Research
- Retinal Development and Disorders
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Genetic Mapping and Diversity in Plants and Animals
- Dysphagia Assessment and Management
- Cancer Cells and Metastasis
- Metabolism and Genetic Disorders
- Empathy and Medical Education
- Rheumatoid Arthritis Research and Therapies
- Genetic and phenotypic traits in livestock
- Systemic Sclerosis and Related Diseases
- BRCA gene mutations in cancer
- Statistical Methods in Clinical Trials
- Genetic factors in colorectal cancer
- Bioinformatics and Genomic Networks
- CRISPR and Genetic Engineering
- Evolutionary Game Theory and Cooperation
- Lung Cancer Diagnosis and Treatment
- Inflammatory Myopathies and Dermatomyositis
- Gene expression and cancer classification
- Dermatology and Skin Diseases
Japan Science and Technology Agency
2016-2025
National Cancer Centre Japan
2020-2025
Fujita Health University
2006-2024
National Cancer Research Institute
2024
Tokyo Medical and Dental University
2018-2021
The University of Tokyo
2004-2020
Nagoya University
2015-2018
National Institute of Genetics
2013-2015
Research Organization of Information and Systems
2013
Bank of Japan
2013
The germline mutation rate is an important parameter that affects the amount of genetic variation and evolution. However, neither mutations in laboratory mice nor biological significance mammalian populations clear. Here we studied genome-wide rates long-term effects accumulation on phenotype more than 20 generations wild-type C57BL/6 mutator mice, which have high DNA replication error rates. We estimated base-substitution to be 5.4 × 10(-9) (95% confidence interval = 4.6 10(-9)-6.5 10(-9))...
Importance The effect of adjuvant chemotherapy following resection pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) on overall survival (OS) is unclear because current studies do not account for the number cycles regimen. Objective To investigate association with OS, taking into Design, Setting, Participants This retrospective cohort study included...
An alternative approach to investigate associations between genetic variants and disease is examine deviations from the Hardy–Weinberg equilibrium (HWE) in genotype frequencies within a case population, instead of case–control association analysis. The HWE analysis requires cases demonstrates notable ability mapping recessive variants. Allelic heterogeneity common phenomenon diseases. While gene-based successfully incorporates this heterogeneity, there are no such approaches for Therefore,...
Major depressive disorder (MDD) is a complex, heritable psychiatric disorder. Advanced statistical genetics for genome-wide association studies (GWASs) have suggested that the heritability of MDD largely explained by common single nucleotide polymorphisms (SNPs). However, until recently, there has been little success in identifying MDD-associated SNPs. Here, based on an empirical Bayes estimation semi-parametric hierarchical mixture model using summary statistics from GWASs, we show...
Cancer prognosis markers are useful for treatment decisions; however, the omics-level landscape is not well understood across multiple cancer types. Pan-Cancer Analysis of Whole Genomes (PCAWG) provides unprecedented access to various types molecular data, ranging from typical DNA mutations and RNA expressions more deeply analyzed or whole-genomic features, such as HLA haplotypes structural variations. We PCAWG data 13 1,514 patients identify belonging 17 features in survival analysis based...
To identify functional residues of rat liver L-aromatic amino acid decarboxylase (AADC), we aligned the sequences 13 group II decarboxylases and performed mutational analysis on that were invariant or conservatively substituted. Replacements His192, Asp252, Asp271, Ser296, Lys303, Tyr332, Arg355 with alanine decreased AADC activity (kcat/K(m)) by more than 10(4)-fold. Conservative replacements [Asp252-->Glu], [Lys303-->Arg], [Tyr332-->Phe] also resulted in decreases 10(4)-fold, indicating...
Background Even after curative resection, pancreatic ductal adenocarcinoma (PDAC) patients suffer a high rate of recurrence. There is an unmet need to predict which will experience early recurrence resection in order adjust treatment strategies. Methods Data with resectable PDAC undergoing surgical between January 2005 and September 2018 were reviewed stratify for defined as occurring within 6 months resection. Preoperative data including demographics, tumor markers, blood...
Abstract Tameness is a major behavioral factor for domestication, and can be divided into two potential components: motivation to approach humans (active tameness) reluctance avoid (passive tameness). We identified genetic loci active tameness through selective breeding, selection mapping, association analysis. In previous work using laboratory wild mouse strains, we found that strains were predominantly selected passive but not during their domestication. To identify regions associated with...
Purpose . To investigate genetic and clinical features of patients with rhodopsin ( RHO ) mutations in two Japanese families autosomal dominant retinitis pigmentosa (adRP). Methods Whole-exome sequence analysis was performed ten adRP families. Identified for the cosegregation were confirmed by Sanger sequencing. Ophthalmic examinations to evaluate RP phenotypes. The impact mutation on conformation examined molecular modeling analysis. Results In families, we identified (c.377G>T (p.W126L)...
The genetic basis of Japanese autosomal recessive retinitis pigmentosa (ARRP) remains largely unknown. Herein, we applied a 2-step genome-wide association study (GWAS) in 640 patients. Meta-GWAS identified three independent peaks at P < 5.0 × 10-8, all within the major ARRP gene EYS. Two were each linkage disequilibrium with different low frequency variant (allele 0.05); known founder Mendelian mutation (c.4957dupA, p.S1653Kfs*2) and non-synonymous (c.2528 G > A, p.G843E) unknown...
Recently, in 2013 Feder et al. proposed the frequency increment test (FIT), which evaluates natural selection at a single diallelic locus by use of time-series data allele frequencies. This is unbiased under conditions constant population size and no sampling noise. Here, we expand upon FIT introducing that explicitly allows for changes using information from independent reference loci. Various demographic models suggest our irrespective fluctuations when noise can be ignored it has greater...
Aromatic L-amino acid decarboxylase (AADC) in which the pyridoxal 5'-phosphate (PLP)-binding residue Lys303 was replaced by an alanine is virtually inactive as a catalyst. On reaction of normal substrate L-dopa with this mutant AADC, absorption at around 330 nm gradually increased concomitant decrease free PLP molecule 390 nm. Analysis 330-nm absorbing species on HPLC and spectrophotometry showed that it 1:1 adduct dopamine, probably Pictet-Spengler type formed from PLP-dopamine Schiff base....
Genome-wide association studies (GWAS) suggest that the genetic architecture of complex diseases consists unexpectedly numerous variants with small effect sizes. However, polygenic architectures many have not been well characterized due to lack simple and fast methods for unbiased estimation underlying proportion disease-associated their effect-size distribution. Applying empirical Bayes semi-parametric hierarchical mixture models GWAS summary statistics, we confirmed schizophrenia was...
Purpose: We have previously reported clinical features of two siblings, a sister with complete achromatopsia (ACHM) and brother incomplete ACHM, in consanguineous Japanese family. With the current study, we intended to identify disease-causing mutation siblings investigate why phenotypes differed.Methods: performed comprehensive ophthalmic examination for each sibling parent. Whole-exome Sanger sequencing were on genomic DNA. Molecular modeling was analyzed an silico study.Results: The...
<h3>Background:</h3> Systemic sclerosis (Scleroderma; SSc) is a rare autoimmune connective tissue disease characterized by vasculopathy and fibrosis leading to progressive dysfunction of multiple organs. In 90 % patients with SSc, the upper gastrointestinal tract typically involved especially in esophageal lesions such as peristalsis and/or gastroesophageal reflux (GERD) due esophagus. However whether dysphagia an unique organ involvement or associated SSc itself still unclear, since there...
Empathy is widely regarded as being key to effective consultation in general practice. The Consultation and Relational (CARE) Measure a used well-validated patient-rated measure English. A Japanese version of the CARE has undergone preliminary validation, but its ability differentiate between individual doctors not been established. current study sought investigate reliability terms discrimination doctors. We conducted secondary analysis dataset involving 252 patients assessed by nine...
Abstract Bayes factor analysis has the attractive property of accommodating risks both false negatives and positives when identifying susceptibility gene variants in genome-wide association studies (GWASs). For a particular SNP, critical aspect this is that it incorporates probability obtaining observed value statistic on disease under alternative hypotheses non-null association. An approximate (ABF) was proposed by Wakefield (Genetic Epidemiology 2009;33:79–86) based normal prior for...
Abstract To uncover genetic basis of autosomal recessive retinitis pigmentosa (ARRP), we applied 2-step genome-wide association study (GWAS) in 640 Japanese patients prescreened with targeted re-sequencing. Meta-GWAS identified three independent peaks at P < 5.0×10 -8 , all within the major ARRP gene EYS . Two were each tagged by a low frequency variant (allele 0.05); known founder Mendelian mutation (c.4957dupA, p.S1653Kfs*2) and presumably hypomorphic non-synonymous (c.2528G>A,...
Abstract Genome-wide association studies (GWAS) suggest that the genetic architecture of complex diseases consists unexpectedly numerous variants with small effect sizes. However, polygenic architectures many have not been well characterized due to lack simple and fast methods for unbiased estimation underlying proportion disease-associated their effect-size distribution. Applying empirical Bayes semi-parametric hierarchical mixture models GWAS summary statistics, we confirmed schizophrenia...