Pathogenicity analysis of ATP7B in pediatric patients with Wilson's disease and functional verification of alternative splice variants.

Background: Wilson's disease (WD) is an autosomal recessive inherited disease caused by ATP7B gene mutations. Some mutations in ATP7B are presumed to be pathogenic by altering pre-mRNA splicing, while most have not been functionally verified. This study aimed to perform functional studies to verify the pathogenicity of variants that may affect pre-mRNA splicing.

Case Report: A novel variant in a Chinese infant with mitochondrial DNA depletion syndrome and collective analyses of variants for disease etiology.

Background: There are few reports of infantile mitochondrial DNA depletion syndrome (MDDS) caused by variants in and the correlation between genotype and phenotype has rarely been analyzed in detail. This study investigated an infantile patient with MDDS, from clinical characteristics to genetic causes.

Methods: Routine physical examinations, laboratory assays, which included gas chromatography-mass spectrometry of blood and urine, and MRI scans were performed to obtain an exact diagnosis.

A novel mutation in causes combined oxidative phosphorylation deficiency 23 by affecting pre-mRNA splicing.

Background: Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) is a rare mitochondrial disease caused by mutations in the gene. The rare incidence of the disease and the high clinical heterogeneity pose challenges in making a precise diagnosis. Investigations into the rare COXPD23 patients are of pathophysiological and etiological value.

Fine genetic mapping of the chromosome 11q23.3 region in a Han Chinese population: insights into the apolipoprotein genes underlying the blood lipid-lipoprotein variances.

The unusual chromosome 11q23.3 harboring the apolipoprotein (APO) gene cluster has been well documented for its essential roles in plasma lipid-related traits and atherosclerotic cardiovascular diseases. However, its genetic architecture and the potential biological mechanisms underlying complex phenotypes have not been well assessed.

Identification and functional analysis of glycemic trait loci in the China Health and Nutrition Survey.

To identify genetic contributions to type 2 diabetes (T2D) and related glycemic traits (fasting glucose, fasting insulin, and HbA1c), we conducted genome-wide association analyses (GWAS) in up to 7,178 Chinese subjects from nine provinces in the China Health and Nutrition Survey (CHNS). We examined patterns of population structure within CHNS and found that allele frequencies differed across provinces, consistent with genetic drift and population substructure. We further validated 32 previously described T2D- and glycemic trait-loci, including G6PC2 and SIX3-SIX2 associated with fasting glucose.

A functional polymorphism affecting the APOA5 gene expression is causally associated with plasma triglyceride levels conferring coronary atherosclerosis risk in Han Chinese Population.

Apolipoprotein A5 (APOA5) gene plays a key role in plasma triglyceride (TG) metabolism, and shows the involvement in coronary artery disease (CAD). A set of single nucleotide polymorphisms around the APOA5 gene was identified to be associated with plasma TG levels. It is of biological and clinical importance to discern the genuine genetic determinants.

Gene-wide characterization of common quantitative trait loci for ABCB1 mRNA expression in normal liver tissues in the Chinese population.

In order to comprehensively screen genetic variants leading to differential expression of the important human ABCB1 gene in the primary drug-metabolizing organ, ABCB1 mRNA expression levels were measured in 73 normal liver tissue samples from Chinese subjects. A set of Tag SNPs. were genotyped.

Functional evaluation of genetic and environmental regulators of p450 mRNA levels.

Variations in the activities of Cytochrome P450s are one of the major factors responsible for inter-individual differences in drug clearance rates, which may cause serious toxicity or inefficacy of therapeutic drugs. Various mRNA level is one of the key factors for different activity of the major P450 genes. Although both genetic and environmental regulators of P450 gene expression have been widely investigated, few studies have evaluated the functional importance of cis- and trans-regulatory factors and environmental factors in the modulation of inter-individual expression variations of the P450 genes.

Haplotype-based case-control study of the human CYP11B2 gene and essential hypertension in Yi and Hani minorities of China.

This haplotype-based case-control study investigated whether the aldosterone synthase gene (CYP11B2) might be implicated in the pathogenesis of essential hypertension in Yi (226 individuals) and Hani (296 individuals) minorities of China. Four tag SNPs (rs4536, rs4545, rs3097, and rs3802230) and the K173R polymorphism were genotyped using the PCR-RFLP method. In the Hani minority, rs4536 was significantly associated with hypertension, after Bonferroni correction.

Winter temperature and UV are tightly linked to genetic changes in the p53 tumor suppressor pathway in Eastern Asia.

The tumor suppressor p53 is a master sensor of stress. Two human-specific polymorphisms, p53 codon 72 and MDM2 SNP309, influence the activities of p53. There is a tight association between cold winter temperature and p53 Arg72 and between low UV intensity and MDM2 SNP309 G/G in a cohort of 4029 individuals across Eastern Asia that suggests causative selection.

Y-chromosome polymorphisms define the origin of the Mang, an isolated population in China.

The Mang is an isolated population living at the border of Vietnam and China characterized by small stature and a primordial lifestyle. However, the origin of this population remains unclear. To clarify the origin of the Mang and its genetic relationship with other populations, 20 Y-chromosome markers were analyzed, including 12 biallelic markers and eight short tandem repeats (STR) in this population, and the data compared with published data from other populations in eastern Asia.