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GNE myopathy is a heterogeneous group of ultrarare neuromuscular disorders caused by mutations in the GNE gene. An estimated prevalence of 1~21/1,000,000 leads to a deficiency of data and a lack of availability of samples to conduct clinical research on this neuromuscular disorder. Although GNE, which is the mutated gene responsible for the disease, is well known as the key enzyme in the biosynthesis pathway of sialic acid, the clinicopathological‐genetic spectrum of GNE mutant patients is still unclear and expanding. This study presents ten unrelated patients with GNE myopathy, discovering five novel missense mutations. Clinical, electrophysiological, imaging, pathological and genetic data are presented in a retrospective manner. Interestingly, several patients in the cohort were found to have peripheral neuropathy and inflammatory cell infiltration in muscle biopsies, which have seldom been reported. This study, conducted by a neuromuscular centre in China, is the first attempt to highlight these abnormal clinicopathological features and associate them with genetic mutations in GNE myopathy.

Three new metal-organic frameworks (MOFs), namely, [Pb7(TTPCA)4Cl2]·3H2O (1), [Pb7(TTPCA)4(DMA)2(HCOO)2]·H2O (2), and [Pb4(TTPCA)3]·3DMF·2H2O·H3O (3), were synthesized by the H3TTPCA ligand [H3TTPCA = 1,1',1″-(1,3,5-triazine-2,4,6-triyl)-tripiperidine-4-carboxylic acid], with lead(II) nitrate under solvothermal conditions. They were characterized by CHN analysis, IR spectroscopy, UV-vis spectroscopy, and single-crystal and powder X-ray diffraction. In addition, their thermogravimetric analysis and fluorescence properties were studied. Compounds 1-3 were 3D MOF structures with different Pbx(COO)y clusters: ([Pb7(COO)12Cl2]), ([Pb7(COO)12]), and [Pb8(COO)18]. Fluorescence detection of compounds 1-3 shows that they can act as excellent sensors of nitrophenols with a low limit of detection and a high quenching constant.

A series of novel metal–organic frameworks were synthesized by using semirigid ligand 1,1′,1″-(1,3,5-triazine-2,4,6-triyl)tripiperidine-4-carboxylic acid (H3TTPCA) and lead halide (Cl, Br, or I). T...

The problem of pollution caused by highly toxic ions has become the focus of global attention and has attracted the interest of many researchers. However, microdetection using a metal–organic frame...

In 2002, our research group observed a gene clustering pattern based on the base frequency of A versus T at the second codon position in the genome of Vibrio cholera and found that the functional category distribution of genes in the two clusters was different. With the availability of a large number of sequenced genomes, we performed a systematic investigation of A2–T2 distribution and found that 2694 out of 2764 prokaryotic genomes have an optimal clustering number of two, indicating a consistent pattern. Analysis of the functional categories of the coding genes in each cluster in 1483 prokaryotic genomes indicated, that 99.33% of the genomes exhibited a significant difference (p . Specifically, functional category P was overrepresented in the small cluster of 98.65% of genomes, whereas categories J, K, and L were overrepresented in the larger cluster of over 98.52% of genomes. Lineage analysis uncovered that these preferences appear consistently across all phyla. Overall, our work revealed an almost universal clustering pattern based on the relative frequency of A2 versus T2 and its role in functional category preference. These findings will promote the understanding of the rationality of theoretical prediction of functional classes of genes from their nucleotide sequences and how protein function is determined by DNA sequence. Graphical abstract

Three new metal-organic frameworks (MOFs), namely, [Pb

Three new superoxide dismutase model compounds: [CoL(H2O)]·2H2O (1), [CdL(H2O)]·H2O (2) and [PbL] (3) were successfully synthesized by the reaction of a transition metal salt and 5-aminoisophthalic acid under hydrothermal conditions (L: 5-aminoisophthalic acid). The three compounds were characterized by elemental analysis, infrared spectroscopy, ultraviolet–visible spectroscopy, PXRD analysis and TG analysis. X-ray single crystal diffraction analysis showed that compounds 2 and 3 were 3D inorganic–organic framework structures while compound 1 was a 2D structure. These simulations contained pores structures with maximum sizes of 4.08–14.67 A. To further explore the functional properties of these compounds, we firstly analyzed their SOD activity, and the results demonstrated that they have different SOD activities. The IC50 values of the three mimics are much smaller than the international standard for SOD standards, demonstrating that these mimics have superior Reactive Oxygen Species resistance.

Pandemic cholera is a major concern for public health because of its high mortality and morbidity. Mutation accumulation (MA) experiments were performed on a representative strain of the current cholera pandemic. Although the base-pair substitution mutation rates in Vibrio cholerae (1.24 × 10−10 per site per generation for wild-type lines and 3.29 × 10−8 for mismatch repair deficient lines) are lower than that previously reported in other bacteria using MA analysis, we discovered specific high rates (8.31 × 10−8 site/generation for wild-type lines and 1.82 × 10−6 for mismatch repair deficient lines) of base duplication or deletion driven by large-scale copy number variations (CNVs). These duplication–deletions are located in two pathogenic islands, IMEX and the large integron island. Each element of these islands has discrepant rate in rapid integration and excision, which provides clues to the pandemicity evolution of V. cholerae. These results also suggest that large-scale structural variants such as CNVs can accumulate rapidly during short-term evolution. Mismatch repair deficient lines exhibit a significantly increased mutation rate in the larger chromosome (Chr1) at specific regions, and this pattern is not observed in wild-type lines. We propose that the high frequency of GATC sites in Chr1 improves the efficiency of MMR, resulting in similar rates of mutation in the wild-type condition. In addition, different mutation rates and spectra were observed in the MA lines under distinct growth conditions, including minimal media, rich media and antibiotic treatments.

Poor ovarian response is a significant problem encountered during in vitro fertilization and embryo transfer procedures. Many infertile women may suffer from poor ovarian response and its incidence tends to be increasing in young patients nowadays. It is a major cause of maternal infertility because it is associated with low pregnancy and live birth rates. However, the cause of poor ovarian response is not clear. In this study, we extracted microRNAs from human follicular fluid and performed miRNA sequencing to investigate a potential posttranscriptional mechanism underlying poor ovarian response. The results showed that many miRNAs were obviously different between the poor ovarian response and non-poor ovarian response groups. We then performed quantitative polymerase chain reaction, Western blot analysis and used an in vitro culture system to verify the sequencing results and to study the mechanism. Notably, we found that miRNA-15a-5p was significantly elevated in the young poor ovarian response group. Furthermore, we demonstrated that high levels of miR-15a-5p in the young poor ovarian response group repressed granulosa cell proliferation by regulating the PI3K-AKT-mTOR signaling pathway and promoted apoptosis through BCL2 and BAD. This could explain the reduced oocyte retrieval number seen in poor ovarian response patients.

A series of Salen cobalt complexes have been successfully synthesized and they show high catalytic activity for the copolymerization of propylene oxide (PO) and carbon dioxide (CO2), yielding poly(propylene carbonate) (PPC). After optimizing the reaction conditions such as temperature, pressure and reaction time, the catalytic system achieved excellent conversion (99.47%) and showed high catalytic activity with an initial TOF up to 483.18 h−1. The content of carbonate chain of the PPC and head-to-tail connection are 88.92% and 86.79% respectively. PPC starts to decompose at 230°C and completely decomposed at 260°C. The Mn of the PPC is 109.898 kg/mol, and the PDI is 1.65295.

The in-depth study of viral genomes is of great help in many aspects, especially in the treatment of human diseases caused by viral infections. With the rapid accumulation of viral sequencing data, improved, or alternative gene-finding systems have become necessary to process and mine these data. In this article, we present Vgas, a system combining an ab initio method and a similarity-based method to automatically find viral genes and perform gene function annotation. Vgas was compared with existing programs, such as Prodigal, GeneMarkS, and Glimmer. Through testing 5,705 virus genomes downloaded from RefSeq, Vgas demonstrated its superiority with the highest average precision and recall (both indexes were 1% higher or more than the other programs); particularly for small virus genomes (≤ 10 kb), it showed significantly improved performance (precision was 6% higher, and recall was 2% higher). Moreover, Vgas presents an annotation module to provide functional information for predicted genes based on BLASTp alignment. This characteristic may be specifically useful in some cases. When combining Vgas with GeneMarkS and Prodigal, better prediction results could be obtained than with each of the three individual programs, suggesting that collaborative prediction using several different software programs is an alternative for gene prediction. Vgas is freely available at http://cefg.uestc.cn/vgas/ or http://121.48.162.133/vgas/. We hope that Vgas could be an alternative virus gene finder to annotate new genomes or reannotate existing genome.

Background and Aims Gallstone disease (GD) is a common disease of multigenetic origin; however, the major susceptibility loci for GD in human populations remain unidentified. This study aimed to identify the genetic factors contributing to gallstone development in Chinese. Methods A genome-wide scan was conducted in 12 Han Chinese GD families to identify linkage loci. The linkage region showing the highest logarithm of odds score encompasses the sterol 12α-hydroxylase gene (CYP8B1). Replication analysis with an independent sample of 192 GD patients and 192 unrelated, matched controls was carried out to verify the associations between CYP8B1 polymorphisms and GD. Results Three loci (D3S1266, D4S406, and D9S1682) showed suggestive or nominal evidence of linkage in all 12 GD families. The logarithm of odds score of D3S1266 reached 2.71 in the families with late-onset patients. The single nucleotide polymorphism rs3732860 in the 3′-untranslated region of CYP8B1 showed significant association to GD (P = 0.022), and carriers of the A allele had lower risk of GD (odds ratio = 1.46, 95% confidence interval: 1.055–2.034) compared with carriers of the G allele. Conclusions The single nucleotide polymorphism rs3732860 in the 3′-untranslated region of the CYP8B1 gene is associated with risk of GD in Chinese Han and appears to be responsible for the observed linkage with D3S1266.

Motivation Previously constructed classifiers in predicting eukaryotic essential genes integrated a variety of features including experimental ones. If we can obtain satisfactory prediction using only nucleotide (sequence) information, it would be more promising. Three groups recently identified essential genes in human cancer cell lines using wet experiments and it provided wonderful opportunity to accomplish our idea. Here we improved the Z curve method into the λ-interval form to denote nucleotide composition and association information and used it to construct the SVM classifying model. Results Our model accurately predicted human gene essentiality with an AUC higher than 0.88 both for 5-fold cross-validation and jackknife tests. These results demonstrated that the essentiality of human genes could be reliably reflected by only sequence information. We re-predicted the negative dataset by our Pheg server and 118 genes were additionally predicted as essential. Among them, 20 were found to be homologues in mouse essential genes, indicating that some of the 118 genes were indeed essential, however previous experiments overlooked them. As the first available server, Pheg could predict essentiality for anonymous gene sequences of human. It is also hoped the λ-interval Z curve method could be effectively extended to classification issues of other DNA elements. Availability and Implementation http://cefg.uestc.edu.cn/Pheg Supplementary information Supplementary data are available at Bioinformatics online.

The designed steel of Fe-0.25C-1.5Mn-1.2Si-1.5Ni-0.05Nb (wt pct) treated by a novel quenching-partitioning-tempering (Q-P-T) process demonstrates an excellent product of strength and elongation (PSE) at deformed temperatures from 298 K to 573 K (25 °C to 300 °C) and shows a maximum value of PSE (over 27,000 MPa pct) at 473 K (200 °C). The results fitted by the exponent decay law indicate that the retained austenite fraction with strain at a deformed temperature of 473 K (200 °C) decreases slower than that at 298 K (25 °C); namely, the transformation induced plasticity (TRIP) effect occurs in a larger strain range at 473 K (200 °C) than at 298 K (25 °C), showing better mechanical stability. The work-hardening exponent curves of Q-P-T steel further indicate that the largest plateau before necking appears at the deformed temperature of 473 K (200 °C), showing the maximum TRIP effect, which is due to the mechanical stability of considerable retained austenite. The microstructural characterization reveals that the high strength of Q-P-T steels results from dislocation-type martensite laths and dispersively distributed fcc NbC or hcp e-carbides in martensite matrix, while excellent ductility is attributed to the TRIP effect produced by considerable retained austenite.

In this article, a novel quenching–partitioning–tempering (Q–P–T) process was applied to a Fe–0.25C–1.5Mn–1.2Si–1.5Ni–0.05Nb (wt%) hot-rolled steel, and its optimized parameters were obtained by a Gleeble-3500 thermal simulator and salt baths, respectively. Mechanical property results of the as-treated Q–P–T samples show that the Nb-microalloyed low-carbon steels subjected to Q–P–T processes cover a wide spectrum of strength (1200–1500 MPa) and elongation (14–18%), and exhibit excellent product of strength and elongation (21,000–22,000 MPa%). Microstructural characterization indicates that high strength results from dislocation-type martensite laths and dispersively distributed fcc NbC or hcp ɛ-carbides in martensite matrix and good ductility is attributed to transformation induced plasticity (TRIP) effect from plenty of retained austenite flakes between martensite laths.

Background Several studies on the association of tumor necrosis factor alpha (TNF-α) polymorphisms with recurrent pregnancy loss (RPL) risk have reported conflicting results. The present meta-analysis was conducted to provide a more precise estimation of these relationships and to investigate the real association between TNF-α polymorphisms and RPL. Methods An extensive eligible literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library from their inceptions to May 12, 2015. Specific inclusion criteria were used to evaluate articles. The odds ratio (OR) with 95% confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA12.0 software. Results 10 case–control studies including 1430 RPL patients and 1727 healthy controls were identified. Meta-analysis indicated that TNF-α-308G/A (rs1800629) polymorphism in the TNF-α gene correlated with elevated RPL risk whereas no significant association was observed between TNF-α-238G/A (rs361625) and RPL. Conclusions The current meta-analysis demonstrates that TNF-α-308G/A polymorphism in the TNF-α gene is associated with susceptibility to RPL.

Through a series of linkage analyses in a large Chinese family cohort of psoriasis, we previously identified and confirmed a non-HLA psoriasis linkage locus PSORS9 within a small region at 4q31.2–32.1. Within the critical region of the PSORS9 locus, IL-15 has been long recognized as a strong candidate gene for psoriasis. In this study, we investigated the association between IL-15 genetic polymorphisms and psoriasis in a large Chinese sample. Highly significant evidence for association was identified at a single-nucleotide polymorphism (SNP) (g.96516A → T) within the 3′-untranslated region (UTR) of the IL-15 gene ( P =0.00006, after correction for multiple testing). Haplotype analysis using the SNPs within the 3′UTR region also provided strong supporting evidence for association ( P =0.00005), where we identified a haplotype of the 3′UTR region of IL-15 associated with increased risk to psoriasis (odds ratio=1.65). This association was also supported by the results of our expression activity analyses, where we demonstrated that the identified risk haplotype is associated with an increased activity of IL-15. Therefore, we provided early evidence for the important role of IL-15 genetic variants in the pathogenesis of psoriasis, probably by increasing interleukin production and inflammation in the lesions of psoriasis.

Psoriasis linkage to 4q28–32 (PSORS9) was initially identified by our genome-wide scan in 61 Chinese families and subsequently supported by a meta-analysis of five genome-wide linkage scans of European populations. In this study, we performed a follow-up analysis of PSORS9 using an additional 90 families and improved marker coverage. Joint analysis of all 151 families obtained significant linkage evidence (HLOD=4.53, nonparametric linkage (NPL)=4.03 (P=0.000003)) at the marker interval D4S2997–D4S3033, and the same was obtained for the analysis of the independent new families (HLOD=4.33, NPL=3.15 (P=0.00004)). The linkage evidences from the whole families and the new families exceeded the genome-wide criteria for significant linkage. Furthermore, by performing an ordered subset analysis using mean age at onset as a covariate, we demonstrated that evidence for linkage to PSORS9 is concentrated in the early-onset families and suggested that further study of PSORS9 should focus on early-onset patients. This finding is contradictory to what was found in the Icelandic population and, together with other linkage results, suggests that Chinese and European populations are genetically different for linkage to PSORS9, which may partially explain the influence of ethnic factors on the varying prevalence of psoriasis.

HLA-Cw6 is strongly associated with psoriasis and has been suggested to be the PSORS1 gene that confers susceptibility to early-onset psoriasis. In this study of the clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population, we typed HLA-C in a cohort of 679 patients and compared the two groups. Cw*0602-positive patients (n=345) had an earlier disease onset (p < 1 x 10(-5)), more severe disease (p < 1 x 10(-3)), higher frequency of guttate psoriasis (p < 1 x 10(-9)), more affected legs and trunk (p < 1 x 10(-5)), higher incidence of Kobner's phenomenon (p=0.005) and of trauma history (p=0.009). Cw*0602-negative patients (n= 334) had more palmoplantar pustulosis (p=0.004), nail changes (p=0.001) and scalp involvement (p=0.007). However, there was no statistically significant difference between the two groups regarding age, gender, incidence of plaque psoriasis, erythrodermic, inverse, psoriatic arthritis, and the precipitation factors stress and infection. The study showed that Cw*0602-positive patients had some obvious clinical differences from Cw*0602-negative patients in a Han Chinese population, which provides evidence for an HLA-Cw*0602-associated phenotype in psoriasis.

Background Graves’ disease is a female preponderant autoimmune illness and the contribution of the X chromosome to its risk has long been appreciated. However, no X-linked susceptibility loci have been indentified from recent genome-wide association studies (GWAS). Methods We re-examined the X chromosome data from our recent GWAS for Graves’ disease by including males that were previously excluded from the X chromosome analyses. The data were analysed using logistic regression analysis including sex as a covariate, and an additive method assuming X chromosome inactivation, implemented in snpMatrix. Results A cluster of single nucleotide polymorphism (SNPs) at Xq21.1 was found showing association with genome-wide significance, among which rs3827440 was a non-synonymous SNP of GPR174 (Plogistic regression= 9.52×10−8; PsnpMatrix=4.60×10−9; OR=1.76, 95% CI 1.45 to 2.13). The association was reproduced in an independent sample collection set including 4564 Graves’ disease cases and 3968 sex matched controls (combined Plogistic regression=5.53×10−21; combined PsnpMatrix=4.26×10−22; OR=1.69, 95% CI 1.53 to 1.86). Notably, GPR174 was widely expressed in immune related tissues and rs3827440 genotypes were associated with distinct mRNA levels (p=0.002). GPR174 did not show sex biased gene expression in our expression analysis. Resequencing study suggested the contribution of some rare variants in the GPR174 gene region to disease risk with a collapsing p value of 1.16×10−3. Conclusions The finding of an X-linked risk locus for Graves’ disease expands our understanding of the role of the X chromosome in disease susceptibility.

Gallstone disease (GD) is a common disease of multigenetic origin; however, the major susceptibility loci for GD in human populations remain unidentified. This study aimed to identify the genetic factors contributing to gallstone development in Chinese.A genome-wide scan was conducted in 12 Han Chinese GD families to identify linkage loci. The linkage region showing the highest logarithm of odds score encompasses the sterol 12α-hydroxylase gene (CYP8B1). Replication analysis with an independent sample of 192 GD patients and 192 unrelated, matched controls was carried out to verify the associations between CYP8B1 polymorphisms and GD.Three loci (D3S1266, D4S406, and D9S1682) showed suggestive or nominal evidence of linkage in all 12 GD families. The logarithm of odds score of D3S1266 reached 2.71 in the families with late-onset patients. The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of CYP8B1 showed significant association to GD (P = 0.022), and carriers of the A allele had lower risk of GD (odds ratio = 1.46, 95% confidence interval: 1.055-2.034) compared with carriers of the G allele.The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of the CYP8B1 gene is associated with risk of GD in Chinese Han and appears to be responsible for the observed linkage with D3S1266.

To identify the single nucleotide polymorphisms of human CYP8B1gene and explore the association of some of these SNPs with gallstone disease in Chinese population.The exon and part of promoter were sequenced by a fluorescent labeling automatic method to identify and characterize the SNPs in Chinese population. For SNPs with an allelic frequency of over 10%, a case-control study was performed in patients and controls.Eleven SNPs were found within a 5119 bp region. Among them, 1 was in coding region, 5 in promoter and 5 in 3'-UTR. There were 3 novel SNPs and 12 SNPs in SNP database were not found. The allelic frequency of rs3732860 polymorphism showed a significant difference (P = 0.022) in the association study. The subjects with A allele had a significantly lower frequency of gallstone disease than those with G allele (OR = 1.465, 95%CI 1.055 - 2.034, P = 0.023).SNP rs3732860 of CYP8B1 gene is associated with gallstone disease in Chinese population. And A allele may play a protective role in the pathogenesis of gallstone.

PSORS1 (psoriasis susceptibility gene 1) is a major susceptibility locus for psoriasis. Several fine-mapping studies have highlighted a 300-kb candidate region of PSORS1 where multiple biologically plausible candidate genes were suggested. The most recent study has indicated HLA-Cw6 as the primary PSORS1 risk allele within the candidate region in a Caucasian population. In this study, a family-based association analysis of the PSORS1 locus was performed by analyzing 10 polymorphic microsatellite markers from the PSORS1 region as well as HLA-B, HLA-C and CDSN loci in 163 Chinese families of psoriasis. Five marker loci show strong evidence (P, Author Summary Psoriasis is a common skin disease with strong genetic risk. The analysis of psoriatic families with multiple affected individuals has identified several genomic regions that are linked (showing linkage evidence) to the development of psoriasis. Of them, the region on 6p21.3 (PSORS1) is a well-confirmed major risk locus. The identification of the disease risk gene within the PSOR1 locus, however, has been difficult, largely due to the fact that several genes show evidence for association with the disease development and the evidences are highly correlated and hard to be separated from each other. In this study, we performed a fine mapping study of the PSORS1 locus in Chinese families with psoriasis. By analyzing recombinant haplotypes that carry different risk-associated genetic variants within different genes, we were able to separate the genetic effects observed within multiple genes and identify strong supporting evidence for HLA-C to be the primary risk gene of the PSORS1 locus. We have further demonstrated that the genetic variation within the HLA-C gene does not explain the full linkage evidence at the PSORS1 locus, suggesting that there might be other risk genes and/or alleles within the region. Our findings have improved our understanding about the genetic complexity of the PSORS1 locus.

Psoriasis is a heterogeneous disease for which nine linkage loci (PSORS loci 1-5 and PSORS7-10) have been accepted by the Human Genome Nomenclature Committee and an additional 16 potential susceptibility loci have been reported so far. Our previous genome-wide scan in 61 Chinese Han psoriasis vulgaris families found two susceptibility loci at 6p21.3 and 4q31 and additional suggestive linkage evidence at other regions, including 9q33. In this follow-up study, the linkage evidence at 9q33 was further investigated using an expanded sample of 160 families and improved marker coverage. Our follow-up linkage analysis of the 160 families demonstrated strong linkage evidence (Por = 0.000022) throughout a region between 133.38 and 146.23 cM with a maximum nonparametric linkage (NPL) score of 4.64 (P = 0.00000023) and a heterogeneity LOD (HLOD) score of 5.03 (alpha = 46%) at 142.39 cM near the marker D9S290. By stratifying the 160 families into the subtypes of 130 early-onset and 30 late-onset families, we revealed stronger linkage evidence in the early-onset psoriasis families with a maximum multipoint HLOD score of 6.48 (alpha = 58%) and a maximum NPL score of 4.69 (P = 0.00000012) near marker D9S290. Our follow-up study has confirmed a novel susceptibility locus at 9q33-34 for early-onset psoriasis in the Chinese population.

Summary Background. Acrokeratosis verruciformis of Hopf (AKV) is a rare genodermatosis characterized by multiple flat-topped, flesh-coloured papules on the dorsa of hands and feet, and punctuate keratoses on the palms and soles. A mutation in the ATP2A2 gene has been shown to be associated with AKV and with Darier's disease (DD). Objectives. To explore the molecular aetiology of AKV and DD. Methods. We investigated the clinical and histological information in two families and a sporadic case with AKV and one family and a sporadic case with DD in China. Mutation analysis of ATP2A2 was performed by PCR and direct sequencing, and genotyping and linkage analysis performed using six polymorphic microsatellite markers spanning the locus at 12q23–12q24 containing ATP2A2. Results. Mutational analysis showed no mutation in ATP2A2 among the AKV patients, but we found two novel mutations (p.C318F and p.M719fs) in the DD patients. The genotyping and linkage analysis results revealed no linkage evidence of the locus at 12q23–12q24 in a large AKV family. Conclusions. Our findings provide evidence for the genetic heterogeneity of AKV and demonstrate that mutations in genes other than ATP2A2 are responsible for AKV in a proportion of the Chinese population.

Acne inversa (hidradenitis suppurativa) is a chronic relapsing inflammatory skin disease characterized by recurrent draining sinuses and abscesses, predominantly in skin folds that carry terminal hairs and apocrine glands. The genetic basis for this disease is unknown. In this study, we performed a genome-wide scan in a four-generation Chinese family to map the chromosome location of the responsible gene. We first identified a locus at chromosome 1p21.1-1q25.3 with the maximum logarithm of odds (LOD) score of 3.26 at the marker D1S2624 (at recombination fraction=0.00). The other two-point LOD scores >/=3 were observed at markers D1S2695, D1S2726, D1S252, and D1S2777. Haplotype analysis localized this locus to a 76 Mb region flanked by D1S248 and D1S2711. This is the first locus for the inversa acne and will be a starting point towards understanding the molecular mechanisms of this disease.

Several recent studies have demonstrated the possible involvement of the microsomal glutathione S-transferase 2 (MGST2) gene in the pathogenesis of psoriasis. The objectives of this work are to determine whether the genetic polymorphisms of the MGST2 gene were associated with an increased risk of psoriasis in Chinese patients. We first characterized the linkage disequilibrium pattern within MGST2 and identified single-nucleotide polymorphisms (SNPs) for tagging common genetic variants. Genotype- and haplotype-based analyses were then performed by genotyping the Tag SNPs in a large-scale sample of cases and controls. We characterized the linkage disequilibrium pattern within MGST2 using 12 densely distributed SNPs and identified 6 SNPs for tagging common genetic variants. We then performed an association analysis by genotyping the six SNPs in 552 cases and 384 controls, but none of the genotype- and haplotype-based analyses revealed significant evidence for association. We also performed family-based association analysis by genotyping the six SNPs in 95 trios; no evidence for association was identified. Our comprehensive genetic analysis of MGST2 common variants in a large Chinese sample of psoriasis did not provide any supporting evidence for MGST2 to be the susceptibility gene within the PSORS9 locus.

Objective To report and analyze the mutations of the double-stranded RNA–specific adenosine deaminase ( DSRAD ) gene in 2 Chinese pedigrees with dyschromatosis symmetrica hereditaria (DSH). Design Pedigree study. Setting Anhui province of China. Patients Two Chinese families, consisting of 19 individuals (family 1) and 5 individuals (family 2). Interventions We directly performed mutation detection of the DSRAD gene in 2 Chinese families with DSH by sequencing. The whole coding region of DSRAD was amplified by polymerase chain reaction, and products were analyzed by direct sequencing. Main Outcome Measures Frameshift DSRAD gene mutations. Results The c.3513insC (Arg1171fs) mutation was found in all patients but not in the healthy individuals from family 1, and the c.3220_3224delGCATC (Gly1073fs) mutation was found in 2 patients but not in the healthy members of family 2. These 2 mutations were not found in 96 unrelated control individuals. Conclusion Our data suggest that these 2 novel frameshift mutations in the DSRAD gene could cause DSH in the Chinese Han population and add new variants to the repertoire of DSRAD mutations in DSH.

To identify the single nucleotide polymorphisms (SNPs) in the regulatory and coding regions of human SCN7A (sodium channel, voltage-gated, type VII, alpha polypeptide) gene and to investigate the association of some of these SNPs with essential hypertension (EH) in Chinese.The promoter region, exons, as well as part of the introns of SCN7A gene were sequenced by a fluorescent labeling automatic sequencing method to identify and characterize the SNPs in Chinese population. SNP genotyping was performed by PCR-RFLP or direct DNA sequencing in unrelated EH patients and normotensive controls from a Chinese Han population residing in Shanghai area. Case-control studies on seven SNPs were first carried out in 96 patients and 96 normotensive controls. The positive finding was further verified in an extended study containing 288 patients and 288 controls.Thirty-two SNPs were identified through a 13,132 bp sequencing of SCN7A gene. Among them, seven were in regulatory region, ten in coding regions, one in 3'UTR and fourteen in introns. Thirty SNPs were novel SNPs, and a cSNP in exon 18 (SNP021) was associated with hypertension.The SNP021 in the gene SCN7A is associated with essential hypertension of Chinese Han population in Shanghai and the role of SCN7A gene in hypertension deserves to be further analyzed.

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary genodermatosis characterized by hyperpigmented and hypopigmented macules of on the extremities and caused by the mutations in the ADAR gene(also called DSRAD) encoding for RNA-specific adenosine deaminase. Here we reported clinical and molecular findings of 6 Chinese multi-generation families and 2 sporadic patients with DSH. We found that the same mutation could lead to different phenotypes even in the same family and we did not establish a clear correlation between genotypes and phenotypes. Seven novel heterozygous mutations of ADAR were identified, which were c.2433_2434delAG (p.T811fs), c.2197G>T (p.E733X), c.3286C>T (p.R1096X), c.2897G>T (p.C966F), c.2797C>T (p.Q933X), c.2375delT (p.L792fs) and c.3203-2A>G respectively. Our data add new variants to the repertoire of ADAR mutations in DSH. © 2004 Wiley-Liss, Inc.

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. In addition, imputation was performed within a 500 kb region around the ABCB1 gene using the reference panels of 1,000 Genome project and HapMap III. Bayesian regression was used to assess the strength of associations by compute Bayes Factors for imputed SNPs. Through imputation and linkage disequilibrium analysis, the imputed loci rs28373093, rs1002205, rs1029421, rs2285647, and rs10235835, may represent independent and strong association signals. rs28373093, a polymorphism 1.5 kb upstream from the ABCB1 transcription start site, has the strongest association. 2677 G>A/T and 3435C>T confer a clear gene-dosage effect on ABCB1 mRNA expression. The systematic characterization of gene-wide common quantitative trait loci associated with ABCB1 mRNA expression in normal liver tissues would provide the candidate markers to ABCB1-relevant clinical phenotypes in Chinese population.

Background The beta-2-Adrenergic receptor (ADRB2) gene on chromosome 5q33.1 is an important immunoregulatory factor. We and others have previously implicated chromosomal region 5q31-33 for contribution to the genetic susceptibility to Graves disease (GD) in East-Asian populations. Two recent studies showed associations between the single nucleotide polymorphism (SNP) rs1042714 in the ADRB2 gene and GD. In this study, we aimed to fully investigate whether the ADRB2 gene conferred susceptibility to GD in Chinese population, and to perform a meta-analysis of association between ADRB2 and GD. Methods Approximately 1 kb upstream the transcription start site and the entire coding regions of the ADRB2 gene were resequenced in 48 Han Chinese individuals to determine the linkage disequilibrium (LD) patterns. Tag SNPs were selected and genotyped in a case-control collection of 1,118 South Han Chinese subjects, which included 428 GD patients and 690 control subjects. A meta-analysis was performed with the data obtained in the present samples and those available from prior studies. Results Fifteen SNPs in the ADRB2 gene were identified by resequencing and one SNP was novel. Ten tag SNPs were investigated further to assess association of ADRB2 in the case-control collection. Neither individual tag SNP nor haplotypes showed association with GD in Han Chinese population (P > 0.05). Our meta-analysis of the ADRB2 SNP rs1042714 measured heterogeneity between the ethnic groups (I2 = 53.1%) and no association to GD was observed in the overall three studies with a random effects model (OR = 1.13, 95% CI, 0.95 to 1.36; P = 0.18). However, significant association was found from the combined data of Caucasian population with a fixed effects model (OR = 1.18, 95% CI, 1.06 to 1.32; P = 0.002; I2 = 5.9%). Conclusion Our study indicated that the ADRB2 gene did not exert a substantial influence on GD susceptibility in Han Chinese population, but contributed to a detectable GD risk in Caucasian population. This inconsistency resulted largely from between-ethnicity heterogeneity.

Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic keratinization disorder, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. Thus far, although two loci for DSAP have been identified, the genetic basis and pathogenesis of this disorder have not been elucidated yet. In this study, we performed a genome-wide linkage analysis in three Chinese affected families and localized the gene in an 8.0 cM interval defined by D12S330 and D12S354 on chromosome 12. Upon screening 30 candidate genes, we identified a missense mutation, p.Ser63Asn in SSH1 in one family, a frameshift mutation, p.Ser19CysfsX24 in an alternative variant (isoform f) of SSH1 in another family, and a frameshift mutation, p.Pro27ProfsX54 in the same alternative variant in one non-familial case with DSAP. SSH1 encodes a phosphatase that plays a pivotal role in actin dynamics. Our data suggested that cytoskeleton disorganization in epidermal cells is likely associated with the pathogenesis of DSAP.