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Research Interests: Genetics, Computer Science, Forensic Science, Polymorphism, Population Genetics, and 13 moreSystems Biology, Biology, Personalized Medicine, Copy Number Variation, Single Nucleotide Polymorphism, Genotyping, Linkage Disequilibrium, Genetic Polymorphism, Genetic variation, Interactive graphics, Genetic Analysis, Large Scale, and Thais
Summary Background Canonical and non-canonical WNT signaling are important for odontogenesis. WNT ligand secretion mediator (WLS; MIM611514) is required to transport lipid-modified WNT proteins from the Golgi to the cell membrane, where... more
Summary Background Canonical and non-canonical WNT signaling are important for odontogenesis. WNT ligand secretion mediator (WLS; MIM611514) is required to transport lipid-modified WNT proteins from the Golgi to the cell membrane, where canonical and non-canonical WNT proteins are released into the extracellular milieu. Biallelic pathogenic variants in WLS are implicated in autosomal recessive Zaki syndrome (ZKS; MIM 619648), the only genetic condition known to be caused by pathogenic variants in WLS. Objective To investigate molecular etiology of dental anomalies in 250 patients with or without oral exostoses. Patients and methods Clinical and radiographic examination, and whole exome sequencing, were performed in the case of 250 patients with dental anomalies with or without oral exostoses. Results Four extremely rare heterozygous missense variants (p.Ile20Thr, p.Met46Leu, p.Ser453Ile and p.Leu516Phe) in WLS were identified in 11 patients with dental anomalies. In five of these patients, a torus palatinus or a torus mandibularis was observed. Conclusion We report for the first time the heterozygous WLS variants in patients with dental anomalies. Root maldevelopments in patients with WLS variants supports the role of canonical and non-canonical WNT signaling in root development. We also show that variants in WLS were implicated in torus palatinus and torus mandibularis. In addition, this is the first time that heterozygous carriers of WLS variants were found to manifest phenotypes. WLS variants were likely to have adverse effects on the concentration of WNT ligands delivered to the cell membrane, resulting in aberrant canonical and non-canonical WNT signaling, and subsequent phenotypes. Limitations of the study Patient’s positioning during the acquisition of panoramic radiography might have affected the appearance of the tooth structures. If we had all family members of each patient to study co-segregation between genotype and phenotype, it would have strengthened the association of WLS variants and the phenotypes.
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Introduction: Inactivating mutations of the calcium-sensing receptor (CASR) gene result in neonatal severe hyperparathyroidism (NSHPT). Total parathyroidectomy is an effective way to control life-threatening hypercalcemia in NSHPT but... more
Introduction: Inactivating mutations of the calcium-sensing receptor (CASR) gene result in neonatal severe hyperparathyroidism (NSHPT). Total parathyroidectomy is an effective way to control life-threatening hypercalcemia in NSHPT but leads to permanent hypoparathyroidism. An alternative surgical option is subtotal parathyroidectomy. However, few cases were reported in the literature. Here, we report two unrelated NSHPT patients, one with a novel homozygous mutation (c.1817T>C; p.Leu606Pro) in CASRand the other with heterozygous for the same mutation who also carried two rare intronic variants in CASR. The outcomes of subtotal parathyroidectomy in these patients are also described. Case Presentation: Two infants presented with an alteration of consciousness, respiratory distress, and bradycardia. Severe hypercalcemia, hypophosphatemia, and markedly elevated parathyroid hormone levels were identified, suggesting NSHPT. Cinacalcet was unable to control calcium (Ca) levels of both patients. A novel heterozygous and homozygous missense mutation c.1817T>C; p.Leu606Pro was identified in patients 1 and 2, respectively. Based on the model prediction, proline substitution at Leu606 is likely to disrupt conversion between the active and inactive conformations at the extracellular to transmembrane domain interface of CASR. In addition, two extremely rare intronic variants in CASR (chr3:g.122180314A>G and chr3:g.122251601G>A, based on GRCh38) were identified in patient 1 and his mother. These variants might have contributed to the clinical manifestations of patient 1 who was heterozygous for the c.1817T>C; p.Leu606Pro variant. Subtotal parathyroidectomy was performed by removing three and a half parathyroid glands. So far, patient 1 has been in normocalcemia for 5 years. Patient 2 was in normocalcemia for 16 months after surgery and subsequently developed mild hypoparathyroidism which required only low-dose calcitriol treatment. Conclusion: We report a novel heterozygous and homozygous missense variant (c.1817T>C; p.Leu606Pro) in CASR in two NSHPT patients. The mutation likely disrupts conformational changes of CASR and results in cinacalcet unresponsiveness. Intronic variants in CASR identified in the patient with heterozygous variant might have contributed to the clinical manifestations of the patient. Although total parathyroidectomy is widely accepted as a standard treatment for NSHPT, we demonstrate that subtotal parathyroidectomy is also an effective procedure to normalize Ca levels and allow these patients to be in normocalcemia or mild hypoparathyroidism, which is simply controlled by low-dose calcitriol treatment. Subtotal parathyroidectomy appeared to be an effective treatment for NSHPT regardless of the molecular etiologies.
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The calculation of pairwise correlation coefficient on a dataset, known as the correlation matrix, is often used in data analysis, signal processing, pattern recognition, image processing, and bioinformatics. With the state-of-the-art... more
The calculation of pairwise correlation coefficient on a dataset, known as the correlation matrix, is often used in data analysis, signal processing, pattern recognition, image processing, and bioinformatics. With the state-of-the-art Graphic Processing Units (GPUs) that consist of massive cores capable to do processing up to several Gflops, the calculation of correlation matrix can be accelerated several times over traditional
Research Interests: Bioinformatics, Computer Science, Parallel Computing, Image Processing, Data Analysis, and 15 moreComputational Science, Parallel Processing, MPI, Data Center, CUDA, Message Passing, CoProcessors, Load Balance, Correlation coefficient, Massively parallel computing, Parallel Computer, Coarse Grained Soil, Data Partitioning, Kernel Function, and Correlation Matrix
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Research Interests: Computer Science, Genomics, Computational Biology, Chromatography, Biology, and 15 moreMedicine, OPERATING SYSTEM, Biological Sciences, Genetics of complex disease, Humans, Automation, Mathematical Sciences, BMC Bioinformatics, Genetic variation, Base Sequence, Nucleotides, Automatic Detection, BMC, Nucleotide sequence, and Genetic predisposition to disease
Research Interests: Genetics, Computer Graphics, Computational Biology, MicroRNA, Biology, and 15 moreMedicine, Gene expression, Multidisciplinary, Humans, Gene ontology, Gene, Experimental Study, PLoS one, Database Integration, microRNAs, Genome sequence, Experimental Validation, CpG island, Binding Site, and binding sites
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Research Interests: Computer Graphics, Polymorphism, Computational Biology, Population Genetics, Public Domain, and 15 moreBiology, Life Sciences, Molecular Genetics, Medicine, Biological Sciences, Mutation, Graphic User Interface Design, Primer design, Polymerase Chain Reaction, Design Tool, Computer User Interface Design, Internet, alleles, BMC, and Medical and Health Sciences
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Research Interests: Computer Science, Algorithms, Artificial Intelligence, Human Genetics, Population Genetics, and 15 moreBiology, Medicine, Biological Sciences, Population, Humans, Mathematical Sciences, Haplotypes, Animals, BMC Bioinformatics, Cattle, Human Genome, Large Dataset Analysis, Parametric analysis, population groups, and BMC
Research Interests: Genetics, Computer Science, Algorithms, Computational Biology, Population Genetics, and 15 morePrincipal Component Analysis, Biology, Life Sciences, Stratification, Medicine, Biological Sciences, Population structure, Population, Humans, Mathematical Sciences, Animals, BMC Bioinformatics, Genetic variation, Pruning, and Sciences Du Vivant
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Cryptococcal meningoencephalitis caused by Cryptococcus neoformans infection is the most common cause of death in HIV/AIDS patients. Macrophages are pivotal for the regulation of immune responses to cryptococcal infection by either... more
Cryptococcal meningoencephalitis caused by Cryptococcus neoformans infection is the most common cause of death in HIV/AIDS patients. Macrophages are pivotal for the regulation of immune responses to cryptococcal infection by either playing protective function or facilitating fungal dissemination. However, the mechanisms underlying macrophage responses to C. neoformans remain unclear. To analyze the transcriptomic changes and identify the pathogenic factors of macrophages, we performed a comparative transcriptomic analysis of alveolar macrophage responses during C. neoformans infection. Alveolar macrophages isolated from C. neoformans–infected mice showed dynamic gene expression patterns, with expression change from a protective M1 (classically activated)–like to a pathogenic M2 (alternatively activated)–like phenotype. Arg1, the gene encoding the enzyme arginase 1, was found as the most upregulated gene in alveolar macrophages during the chronic infection phase. The in vitro inhibition of arginase activity resulted in a reduction of cryptococcal phagocytosis, intracellular growth, and proliferation, coupled with an altered macrophage response from pathogenic M2 to a protective M1 phenotype. In an in vitro model of the blood–brain barrier, macrophage-derived arginase was found to be required for C. neoformans invasion of brain microvascular endothelium. Further analysis of the degree of virulence indicated a positive correlation between arginase 1 expression in macrophages and cryptococcal brain dissemination in vivo. Thus, our data suggest that a dynamic macrophage activation that involves arginase expression may contribute to the cryptococcal disease by promoting cryptococcal growth, proliferation, and the invasion to the brain endothelium.
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Research Interests: Bioinformatics, Computer Science, Biotechnology, Data Compression, Developing Countries, and 15 moreDatabase Management Systems, Biological Sciences, Computer Network, Automation, Developing Country, Data, Article, Computer Program, Computer communication networks, Controlled Study, Bittorrent, Database, Computer Interface, Biological Database, and Biological Data
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Nonthaburi3053, Nonthaburi5069 and Nonthaburi13838 isolate of Mycobacterium tuberculosis from TB meningitis patients
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Background: Generalized pustular psoriasis (GPP; MIM 614204) is a rare multisystemic autoinflammatory disease, characterized by episodes of acute generalized erythema and scaling developed with the spread of numerous sterile pustules.... more
Background: Generalized pustular psoriasis (GPP; MIM 614204) is a rare multisystemic autoinflammatory disease, characterized by episodes of acute generalized erythema and scaling developed with the spread of numerous sterile pustules. Adult-onset immunodeficiency syndrome (AOID) with anti-interferon-γ autoantibodies is an immunodeficiency disorder associated with disruptive IFN-γ signaling. Methods: Clinical examination and whole exome sequencing (WES) were performed on 32 patients with pustular psoriasis phenotypes and 21 patients with AOID with pustular skin reaction. Histopathological and immunohistochemical studies were performed. Results: WES identified four Thai patients presenting with similar pustular phenotypes—two with a diagnosis of GPP and the other two with AOID—who were found to carry the same rare TGFBR2 frameshift mutation c.458del; p.Lys153SerfsTer35, which is predicted to result in a marked loss of functional TGFBR2 protein. The immunohistochemical studied showed o...
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Background: Supernumerary teeth refer to extra teeth that exceed the usual number of dentitions. A mesiodens is a particular form of supernumerary tooth, which is located in the premaxilla region. The objective of the study was to... more
Background: Supernumerary teeth refer to extra teeth that exceed the usual number of dentitions. A mesiodens is a particular form of supernumerary tooth, which is located in the premaxilla region. The objective of the study was to investigate the genetic etiology of extra tooth phenotypes, including mesiodens and isolated supernumerary teeth. Methods: Oral and radiographic examinations and whole-exome sequencing were performed on every patient in our cohort of 122 patients, including 27 patients with isolated supernumerary teeth and 94 patients with mesiodens. A patient who had multiple supernumerary teeth also had odontomas. Results: We identified a novel (c.8498A>G; p.Asn2833Ser) and six recurrent (c.1603C>T; p.Arg535Cys, c.5852G>A; p.Arg1951His, c.6949A>T; p.Thr2317Ser; c.1549G>A; p.Val517Met, c.1921A>G; p.Thr641Ala, and c.850G>C; p.Val284Leu) heterozygous missense variants in FREM2 in eight patients with extra tooth phenotypes. Conclusions: Biallelic variant...
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Background: Enamel knots and Hertwig epithelial root sheath (HERS) regulate the growth and folding of the dental epithelium, which subsequently determines the final form of tooth crown and roots. We would like to investigate the genetic... more
Background: Enamel knots and Hertwig epithelial root sheath (HERS) regulate the growth and folding of the dental epithelium, which subsequently determines the final form of tooth crown and roots. We would like to investigate the genetic etiology of seven patients affected with unique clinical manifestations, including multiple supernumerary cusps, single prominent premolars, and single-rooted molars. Methods: Oral and radiographic examination and whole-exome or Sanger sequencing were performed in seven patients. Immunohistochemical study during early tooth development in mice was performed. Results: A heterozygous variant (c. 865A>G; p.Ile289Val) in CACNA1S was identified in all the patients, but not in an unaffected family member and control. Immunohistochemical study showed high expression of Cacna1s in the secondary enamel knot. Conclusions: This CACNA1S variant seemed to cause impaired dental epithelial folding; too much folding in the molars and less folding in the premolars...
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microPIR2: a comprehensive database for human–mouse comparative study of microRNA–promoter interactions
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Cryptococcal meningoencephalitis caused by Cryptococcus neoformans infection is the most common cause of death in HIV/AIDS patients. Macrophages are pivotal for the regulation of immune responses to cryptococcal infection by either... more
Cryptococcal meningoencephalitis caused by Cryptococcus neoformans infection is the most common cause of death in HIV/AIDS patients. Macrophages are pivotal for the regulation of immune responses to cryptococcal infection by either playing protective function or facilitating fungal dissemination. However, the mechanisms underlying macrophage responses to C. neoformans remain unclear. To analyze the transcriptomic changes and identify the pathogenic factors of macrophages, we performed a comparative transcriptomic analysis of alveolar macrophage responses during C. neoformans infection. Alveolar macrophages isolated from C. neoformans–infected mice showed dynamic gene expression patterns, with expression change from a protective M1 (classically activated)–like to a pathogenic M2 (alternatively activated)–like phenotype. Arg1, the gene encoding the enzyme arginase 1, was found as the most upregulated gene in alveolar macrophages during the chronic infection phase. The in vitro inhibit...
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Objective: To report the clinical and radiographic findings and molecular etiology of the first monozygotic twins affected with Pfeiffer syndrome. Methods: Clinical and radiographic examination and whole exome sequencing were performed on... more
Objective: To report the clinical and radiographic findings and molecular etiology of the first monozygotic twins affected with Pfeiffer syndrome. Methods: Clinical and radiographic examination and whole exome sequencing were performed on two monozygotic twins with Pfeiffer syndrome. Results: An acceptor splice site mutation in FGFR2 (c.940-2A>G) was detected in both twins. The father and both twins shared the same haplotype, indicating that the mutant allele was from their father’s chromosome who suffered severe upper airway obstruction and subsequent obstructive sleep apnea. Hypertrophy of nasal turbinates appears to be a newly recognized finding of Pfeiffer syndrome. Increased intracranial pressure in both twins were corrected early by fronto-orbital advancement with skull expansion and open osteotomy, in order to prevent the more severe consequences of increased intracranial pressure, including hydrocephalus, the bulging of the anterior fontanelle, and the diastasis of suture...
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BACKGROUND Mutations in SLC4A4 have been reported to be associated with proximal renal tubular acidosis (RTA), short stature, band keratopathy, cataract, glaucoma, and hypoplastic-type amelogenesis imperfecta. In this study, the authors... more
BACKGROUND Mutations in SLC4A4 have been reported to be associated with proximal renal tubular acidosis (RTA), short stature, band keratopathy, cataract, glaucoma, and hypoplastic-type amelogenesis imperfecta. In this study, the authors describe the clinical manifestations, and investigate the molecular etiology, in a patient with RTA. CASE DESCRIPTION The authors report on a girl with distal RTA who carried a novel homozygous base substitution of 2 consecutive base pair variants (NM_001098484.3:c.808-2A>C and NM_001098484.3:c.808-1G>C) in the SLC4A4 gene. The patient had clinical manifestations of autoimmune thyroiditis and distal RTA, including hypercalciuria, nephrocalcinosis, and nephrolithiasis. In addition to the presence of hypoplastic-type amelogenesis imperfecta, generalized enamel hypomaturation, a feature seen in mice lacking Slc4a4, was also observed in the patient. The basic defect in this patient appeared to be impaired hydrogen ion secretion, leading to an inability to acidify the urine, resulting in alkaline urine (despite a normal serum anion gap), hypokalemic, and hyperchloremic metabolic acidosis. The pulp stones found in the patient may likely be the consequences of a disrupted acid-base homeostatic environment that precipitated mineral deposits. Even with proper treatments for distal RTA, the patient has had frequent recurrences of band keratopathy, pupillary membrane, and cataract. PRACTICAL IMPLICATIONS This is the first report of distal RTA, autoimmune thyroiditis, tooth agenesis, enamel hypomaturation, and pulp stones associated with an SLC4A4 mutation. It is important for dentists to be aware that amelogenesis imperfecta in patients may be a sign of systemic diseases including RTA, nephrocalcinosis, or nephrolithiasis.
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Dengue virus (DENV) is transmitted by mosquitoes to humans, infecting 390 million individuals per year globally. About 20% of infected patients shows a spectrum of clinical manifestation, ranging from a mild flu-like syndrome, to dengue... more
Dengue virus (DENV) is transmitted by mosquitoes to humans, infecting 390 million individuals per year globally. About 20% of infected patients shows a spectrum of clinical manifestation, ranging from a mild flu-like syndrome, to dengue fever, to life-threatening severe dengue diseases, including dengue hemorrhagic fever and dengue shock syndrome.
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microPIR2: a comprehensive database for human–mouse comparative study of microRNA–promoter interactions
Quantitative polymerase chain reaction analysis by deconvolution of internal standard
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Research Interests: Geography, Population Genetics, Biology, Thailand, Medicine, and 15 moreMultidisciplinary, Thai, Earth and Environmental Sciences, Biological Sciences, Population, Humans, Asia, Phenotype, Mainland, PLoS one, Genotype, Single Nucleotide Polymorphism, Peopling, Asian Continental Ancestry Group, and Demographic History
Background Genome-wide association studies (GWAS) do not provide a full account of the heritability of genetic diseases since gene-gene interactions, also known as epistasis are not considered in single locus GWAS. To address this... more
Background Genome-wide association studies (GWAS) do not provide a full account of the heritability of genetic diseases since gene-gene interactions, also known as epistasis are not considered in single locus GWAS. To address this problem, a considerable number of methods have been developed for identifying disease-associated gene-gene interactions. However, these methods typically fail to identify interacting markers explaining more of the disease heritability over single locus GWAS, since many of the interactions significant for disease are obscured by uninformative marker interactions e.g., linkage disequilibrium (LD). Results In this study, we present a novel SNP interaction prioritization algorithm, named iLOCi (Interacting Loci). This algorithm accounts for marker dependencies separately in case and control groups. Disease-associated interactions are then prioritized according to a novel ranking score calculated from the difference in marker dependencies for every possible pai...