OBJECTIVES: To study the association of β2-drenergic receptor ( METHODS: A total of 143 children with asthma who attended the hospital from October 2016 to October 2020 were enrolled as the asthma group, among whom 61 children had mild symptoms (mild group) and 82 children had moderate-to-severe symptoms (moderate-to-severe group). A total of 137 healthy children were enrolled as the control group. Peripheral venous blood samples were collected from the two groups. The SNaPshot SNP technique was used to analyze the SNP and haplotypes of the RESULTS: Polymorphisms were observed in the CONCLUSIONS SNP/haplotype of the
Asthma/genetics* ; Case-Control Studies ; Child ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic, beta-2/genetics* ; Regulatory Sequences, Nucleic Acid

OBJECTIVE: To explore the pathogenesis for a SRY-negative male with 46,XX disorder of sex development (DSD). METHODS: Peripheral blood samples of the patient and his family members were subjected to chromosomal karyotyping, routine PCR, real-time fluorescence quantitative PCR, whole exome sequencing and whole genome sequencing. The data was analyzed with NextGENe software. RESULTS: Both the proband and his brother presented a 46,XX karyotype with negative SRY gene, while their father presented normal phenotype and karyotype with positive SRY gene. No pathogenic variant associated with sex development was detected by whole exome sequencing, while a 243 kb duplication was detected by whole genome sequencing in the 5' upstream region of the SOX9 gene in the proband, his brother and father. The same duplication was not found in his sister and mother. CONCLUSION The 243 kb duplication at the 5' upstream of the SOX9 gene may predispose to the 46,XX DSD in this family. It is speculated that there exist an unknown core regulatory element in the upstream of the SOX9, and its duplication may trigger expression of SOX9 and initiate testicular differentiation in the absence of SRY gene.
Disorders of Sex Development/genetics* ; Female ; Humans ; Male ; Mutation/genetics* ; Regulatory Sequences, Nucleic Acid/genetics* ; Sex-Determining Region Y Protein/genetics* ; Testis ; Whole Exome Sequencing

BACKGROUND/AIMS: α-Fetoprotein (AFP) is normally <10 ng/mL in adults without malignancy or liver regeneration. However, hereditary or nonhereditary persistence of AFP in healthy adults may be encountered in clinical practice. This study describes four cases of persistent AFP elevation in healthy adults and investigates mutations in key transcription regulatory regions of the AFP gene as potential drivers of AFP overexpression. METHODS: Four healthy adults with persistently elevated AFP levels (12.1 to 186.1 ng/mL) for >1 year, and 20 controls with low AFP levels (<0.61 to 2.9 ng/mL) were included in the study. AFP levels were collected from the families of two of the patients. We sequenced five regions that are critical for AFP expression: a promoter, two enhancers, and two silencers. RESULTS: One of the two cases in which family information was represented is the first case of hereditary persistence of AFP in South Korea. Mutations related to AFP overexpression were not found in the transcription regulatory regions among the four patients. CONCLUSIONS: Persistent AFP elevation is a heterogeneous condition with or without a hereditary pattern and may be caused by factors outside of transcription regulatory region changes. Further research on the mechanism of AFP elevation is needed.
Adult* ; alpha-Fetoproteins ; Biomarkers ; DNA Mutational Analysis ; Humans ; Korea ; Liver Regeneration ; Regulatory Sequences, Nucleic Acid

OBJECTIVETo identify the causative mutations in two Chinese Han families featuring triphalangeal thumbs (TPT) and preaxial polydactyly (PPD).

METHODSBlood samples were collected from 9 members (2 affected) from family 1 and 14 members (7 affected) from family 2. After genomic DNA was extracted, the ZPA regulatory sequence (ZRS) region was analyzed with real-time quantitative PCR (qPCR) and Sanger sequencing. For family 1, haplotypes compassing the ZRS were also analyzed with short tandem repeats (STR) and single nucleotide changes.

RESULTSNo copy number mutation around the ZRS region was found in both families. Two heterogeneous mutations in the ZRS (406A>G and 105C>G) were found to co-segregate with the TPT/PPD malformation in family 1 and 2, respectively. Neither mutation was detected in 200 healthy individuals. Haplotype analysis and Sanger sequencing of family 1 indicated that the first TPT/PPD patient in the family was both germline and somatic mosaic for the 406A>G mutation.

CONCLUSIONTwo pathogenic ZRS mutations, 105C>G and 406A>G, have been identified in two Chinese Han families with TPT/PPD, among which the 406A>G mutation was de novo.

Asian Continental Ancestry Group ; genetics ; Female ; Hand Deformities, Congenital ; genetics ; Haplotypes ; Humans ; Male ; Mutation ; Polydactyly ; genetics ; Regulatory Sequences, Nucleic Acid ; Thumb ; abnormalities

DNA microarray and next-generation sequencing provide data that can be used for the genetic analysis of multiple quantitative traits such as gene expression levels, transcription factor binding profiles, and epigenetic signatures. In particular, chromatin opening is tightly coupled with gene transcription. To understand how these two processes are genetically regulated and associated with each other, we examined the changes of chromatin accessibility and gene expression in response to genetic variation by means of quantitative trait loci mapping. Regulatory patterns commonly observed in yeast and human across different technical platforms and experimental designs suggest a higher genetic complexity of transcription regulation in contrast to a more robust genetic architecture of chromatin regulation.
Chromatin* ; Epigenesis, Genetic ; Epigenomics ; Gene Expression ; Genetic Variation ; Humans ; Oligonucleotide Array Sequence Analysis ; Quantitative Trait Loci ; Regulatory Sequences, Nucleic Acid ; Research Design ; Transcription Factors ; Yeasts

Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE) data: type 2 diabetes mellitus (DM), hypertension (HT), and coronary artery disease (CAD). We showed that epistatic single-nucleotide polymorphisms (SNPs) were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012), which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE). Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.
Coronary Artery Disease ; Deoxyribonuclease I ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; DNA ; Gene Expression ; Genome-Wide Association Study ; Hypertension ; Korea ; Polymorphism, Single Nucleotide ; Regulatory Sequences, Nucleic Acid ; Transcription Factors

Monocyte chemoattractant protein-1 (MCP-1) plays an important role in cardiovascular disease (CVD). Genetic polymorphism in the regulatory regions of MCP-1 could affect MCP-1 expression. The purpose of the study was to explore the possible association of MCP-1 -2518 A/G genetic polymorphism and CVD risk factors in the elderly Korean population. Dietary, anthropometric, and biochemical factors were assessed in 168 subjects. The frequency of A/A, G/A, and G/G genotypes was 14.2%, 45.8%, and 40.0%, respectively. The blood level of MCP-1 was significantly higher in subjects with A/A genotype. The MCP-1 level was significantly higher in A/A genotype with hypercholesterolemia than in other genotypes. Meat intake and percent energy from lipids were significantly positively correlated with the MCP-1 level, especially, stronger in A/A genotype. In the stepwise discriminant analysis, TNF-alpha level, meat intake, HDL-C were associated with MCP-1 in all subjects (model R2 = 24%). TNF-alpha level, sugar intake, cholesterol intake, and meat intake affected MCP-1 in A/A genotype (model R2 = 82%), but not in G/A or G/G. In conclusion, subjects possessing A/A genotype exhibited higher levels of MCP-1 than other genotypes in Korean elders. Further, meat, sugar, and cholesterol intakes affected the MCP-1 level. Therefore, the decrement of meat, sugar, and cholesterol intakes helps to normalize the MCP-1 level and can decrease CVD risk in A/A genotype.
Aged* ; Cardiovascular Diseases* ; Chemokine CCL2 ; Cholesterol ; Genotype ; Humans ; Hypercholesterolemia ; Meat ; Polymorphism, Genetic ; Regulatory Sequences, Nucleic Acid ; Risk Factors* ; Tumor Necrosis Factor-alpha

Catecholamine secretory traits were significantly heritable, as were stress-induced blood pressure changes. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis. In the tyrosine hyroxylase promoter, significant associations were found for urinary catecholamine excretion and for blood pressure response to stress. TH promoter haplotype 2 (TGGG) showed pleiotropy, increasing both norepinephrine excretion and blood pressure during stress. In hypertension, 2 independent case-control studies (1,266 subjects with 53% women and 927 subjects with 24% women) replicated the effect of C-824T in the determination of blood pressure. Chromogranin A (CHGA) plays a fundamental role in the biogenesis of catecholamine secretory granules. Changes in the storage and release of CHGA in clinical and experimental hypertension prompted us to study whether genetic variation at the CHGA locus might contribute to alterations in autonomic function, and hence hypertension and its target organ consequences such as hypertensive kidney disease (nephrosclerosis). Systematic polymorphism discovery across the human CHGA locus revealed such regulatory regions as the proximal promoter and 3'-UTR. In chromaffin cell-transfected CHGA 3'-UTR and promoter/luciferase reporter plasmids, the functional consequences of the regulatory/non-coding allelic variants were documented. Variants in both the proximal promoter and the 3'-UTR displayed statistical associations with hypertension and hypertensive end stage renal disease. Therefore, I would like to review the common genetic variation in TH and CHGA as a cause of inter-individual variation in sympathetic activity, and ultimately blood pressure and hypertensive kidney disease.
Blood Pressure ; Case-Control Studies ; Chromogranin A ; Female ; Genetic Variation ; Genomics ; Haplotypes ; Humans ; Hypertension ; Kidney ; Kidney Diseases ; Kidney Failure, Chronic ; Norepinephrine ; Plasmids ; Regulatory Sequences, Nucleic Acid ; Secretory Vesicles ; Tyrosine ; Tyrosine 3-Monooxygenase ; Organelle Biogenesis

Regulation of gene expression is considered a plausible mechanism of drug addiction given the stability of behavioral abnormalities that define an addicted state. Numerous transcription factors, proteins that bind to regulatory regions of specific genes and thereby control levels of their expression, have been implicated in the addiction process over the past decade or two. Here we review the growing evidence for the role played by several prominent transcription factors, including a Fos family protein (DeltaFosB), cAMP response element binding protein (CREB), and nuclear factor kappa B (NFkappaB), among several others, in drug addiction. As will be seen, each factor displays very different regulation by drugs of abuse within the brain's reward circuitry, and in turn mediates distinct aspects of the addiction phenotype. Current efforts are geared toward understanding the range of target genes through which these transcription factors produce their functional effects and the underlying molecular mechanisms involved. This work promises to reveal fundamentally new insight into the molecular basis of addiction, which will contribute to improved diagnostic tests and therapeutics for addictive disorders.
Chromatin Assembly and Disassembly ; Cyclic AMP Response Element-Binding Protein ; Diagnostic Tests, Routine ; Epigenomics ; Gene Expression Regulation ; Humans ; NF-kappa B ; Nucleus Accumbens ; Phenotype ; Proteins ; Regulatory Sequences, Nucleic Acid ; Reward ; Street Drugs ; Substance-Related Disorders ; Transcription Factors ; Ventral Tegmental Area

OBJECTIVETo study the function of the chalcone synthese gene introns in Scutellaria baicalensis, and clarify preliminarily their role in abiotic stress.

METHODThe CHS introns with specific primers were cloned and bioinformatic method was applied to predict the cis-elements in the intron of CHS. The introns were subcloned into binary vector, pCAMBIA-1301 before being transferred to tobacco. Then the activity of GUS of the transgenic tobacco seeds was analyzed.

RESULTSeven cis-elements were found in the introns. Under the dark and high temperature GUS expression rose at the first (3 h), but then declined (9 h). ABA and MeJA regulated insignificantly the GUS activity in normal temperature; treatment of 10% PEG induced GUS expression.

CONCLUSIONCHS introns could be play a role in the regulation of S. baicalensis phenylpropanoid biosynthetic pathway.

Acyltransferases ; genetics ; Base Sequence ; Gene Expression Regulation, Plant ; drug effects ; Gene Order ; Genetic Vectors ; Introns ; Molecular Sequence Data ; Plants, Genetically Modified ; genetics ; metabolism ; Polyethylene Glycols ; pharmacology ; Regulatory Sequences, Nucleic Acid ; genetics ; Scutellaria baicalensis ; enzymology ; genetics ; Sequence Alignment ; Tobacco ; genetics ; metabolism