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Novel Variants (novel + variants)
Selected AbstractsChemInform Abstract: Chemo-/Regioselective Synthesis of 6-Unsubstituted Dihydropyrimidinones, 1,3-Thiazines and Chromones via Novel Variants of Biginelli Reaction.CHEMINFORM, Issue 37 2009Jie-Ping Wan Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Novel variants within the coding regions of the Slc11A1 gene identified in Bos taurus and Bos indicus breedsJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 1 2008R. Martínez Summary Although in the cow the genetic resistance to brucellosis has been previously attributed to the Slc11A1 gene encoding Nramp1 protein, none of the mutations described to date seems to be the cause. To be able to associate another polymorphism of the gene to brucellosis resistance, we characterized the gene and identified in different breeds of Bos taurus and Bos indicus, six new variants among a total of 11 single nucleotide mutations, of which five occurred in the coding sequence (three are missense mutations), one in the promoter region and five in introns. The allelic and genotypic frequencies calculated revealed differences (p < 0.05) among the breeds studied. [source] Novel variants related to TT virus distributed widely in China,JOURNAL OF MEDICAL VIROLOGY, Issue 1 2002Kangxian Luo Abstract TTV is a DNA virus with high genetic heterogeneity. To investigate the novel isolates of the virus, blood samples were collected from subjects who lived in various parts of China and suffered from hepatitis or were asymptomatic carriers. Nested PCR was carried out to amplify a 3.2-kb fragment using primers deduced from the prototype TTV (TA278). The ten entire 3.2-kb nt sequences were aligned with isolate TA278, SANBAN, TUS01, and SENV retrieved from GenBank, and a phylogenetic tree was constructed by Neighbor-Joining method. The analysis indicated that five novel variants of the present study have not been described before, and all TTV-related isolates could be classified into three groups. The isolate TCHN-A, B and TUS01 were included in a group, and the remaining novel isolates together with SANBAN and TA278 clustered into another group, while SEN virus formed a distinct group. The genetic distances of the five novel variants were 0.5507,0.8476 to TA278, 0.4635,0.7877 to SANBAN, 0.6064,0.7834 to TUS01 and 0.6936,0.8236 to SENV. Of these novel variants, the ORF1 consisted of 426,772 aa and ORF2 of 141,156 aa. The nt identities of ORF1 and ORF2 between those variants and TA278, SANBAN, and TUS01 were 46.1,60.8 and 48.7,63.6%, and those of aa sequences were only 27.1,52.4 and 28.9,45.5%, respectively. The first 65 aa of ORF1 were rich in arginine and most conserved with homology of 56.5,70.0%. There was a hypervariable region from aa 286 to 403 with merely 17.7,27.0% of identity. Despite a low aa identity between TA278 and the variants, they have similar hydrophilicity profiles of ORF1. There were 2,10 N-glycosylation motifs found in these variants. In conclusion, despite the high divergence, sequences of all these isolates shared common genome organisation, ORF structure, hydrophilicity patterns, and some potential motifs with TTV prototype. It is suggested that various TTV and TTV-related isolates belong to a very large and complex family, which remains to be studied. J. Med. Virol. 67:118,126, 2002. © 2002 Wiley-Liss, Inc. [source] Screening for SNCA and LRRK2 mutations in Greek sporadic and autosomal dominant Parkinson's disease: identification of two novel LRRK2 variantsEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2007G. Xiromerisiou Mutations in SNCA and LRRK2 genes, encoding alpha-synuclein and leucine-rich repeat kinase 2, respectively, cause autosomal dominant Parkinson's disease (AdPD). The LRRK2 G2019S (c.6055G > A) and R1441G (c.4321C > G) mutations have also been identified in sporadic PD (sPD). We studied 55 unrelated patients with AdPD, 235 patients with sPD, and 235 healthy age- and gender-matched controls all of Greek origin. Patients with AdPD were screened for SNCA and LRRK2 mutations by direct sequencing. SNCA gene dosage analysis was also performed for AdPD using quantitative duplex polymerase chain reaction of genomic DNA. In addition, we investigated the frequency of the LRRK2 G2019S mutation in sPD. We found no missense mutations or multiplications in the SNCA gene. Here we report two novel variants, A211V (c.632C > T) and K544E (c.1630A > G) in LRRK2 gene in two patients with AdPD that was not present in controls. We identified only one patient with sPD (1/235; 0.4%) carrying the G2019S mutation. LRRK2 mutations are present in AdPD and sPD patients of Greek origin. [source] Functional analysis of mutations in the ATP loop of the Wilson disease copper transporter, ATP7B,HUMAN MUTATION, Issue 5 2010Leiah M. Luoma Abstract Wilson disease (WND) is an autosomal recessive disorder resulting from mutation of ATP7B. Transport of copper by ATP7B from the trans -Golgi of hepatocytes into apical membrane-trafficked vesicles for excretion in the bile is the major means of copper elimination from the body. Although copper is an essential nutrient, homeostasis must be carefully maintained. If homeostasis is disrupted, copper can accumulate within the liver, kidney, cornea, and/or brain. The range of organs affected leads to clinical heterogeneity and difficulty in WND diagnosis. Sequencing of ATP7B is an important adjunct for diagnosis but has led to the discovery of many novel missense variants. Although prediction programs are available, functional characterization is essential for determining the consequence of novel variants. We have tested 12 missense variants localized to the ATP loop of ATP7B and compared three predictive programs (SIFT, PolyPhen, and Align-GVGD). We found p.L1043P, p.G1000R, p.G1101R, p.I1102T, p.V1239G, and p.D1267V deleterious; p.G1176E and p.G1287S intermediate; p.E1173G temperature sensitive; p.T991M and p.I1148T mild; and p.R1228T functioning as wild type. We found that SIFT most often agreed with functional data (92%), compared with PolyPhen (83%) and Align-GVGD (67%). We conclude that variants found to negatively affect function likely contribute to the WND phenotype in patients. Hum Mutat 31:569,577, 2010. © 2010 Wiley-Liss, Inc. [source] Novel variants related to TT virus distributed widely in China,JOURNAL OF MEDICAL VIROLOGY, Issue 1 2002Kangxian Luo Abstract TTV is a DNA virus with high genetic heterogeneity. To investigate the novel isolates of the virus, blood samples were collected from subjects who lived in various parts of China and suffered from hepatitis or were asymptomatic carriers. Nested PCR was carried out to amplify a 3.2-kb fragment using primers deduced from the prototype TTV (TA278). The ten entire 3.2-kb nt sequences were aligned with isolate TA278, SANBAN, TUS01, and SENV retrieved from GenBank, and a phylogenetic tree was constructed by Neighbor-Joining method. The analysis indicated that five novel variants of the present study have not been described before, and all TTV-related isolates could be classified into three groups. The isolate TCHN-A, B and TUS01 were included in a group, and the remaining novel isolates together with SANBAN and TA278 clustered into another group, while SEN virus formed a distinct group. The genetic distances of the five novel variants were 0.5507,0.8476 to TA278, 0.4635,0.7877 to SANBAN, 0.6064,0.7834 to TUS01 and 0.6936,0.8236 to SENV. Of these novel variants, the ORF1 consisted of 426,772 aa and ORF2 of 141,156 aa. The nt identities of ORF1 and ORF2 between those variants and TA278, SANBAN, and TUS01 were 46.1,60.8 and 48.7,63.6%, and those of aa sequences were only 27.1,52.4 and 28.9,45.5%, respectively. The first 65 aa of ORF1 were rich in arginine and most conserved with homology of 56.5,70.0%. There was a hypervariable region from aa 286 to 403 with merely 17.7,27.0% of identity. Despite a low aa identity between TA278 and the variants, they have similar hydrophilicity profiles of ORF1. There were 2,10 N-glycosylation motifs found in these variants. In conclusion, despite the high divergence, sequences of all these isolates shared common genome organisation, ORF structure, hydrophilicity patterns, and some potential motifs with TTV prototype. It is suggested that various TTV and TTV-related isolates belong to a very large and complex family, which remains to be studied. J. Med. Virol. 67:118,126, 2002. © 2002 Wiley-Liss, Inc. [source] Enhanced autophagic cell death in expanded polyhistidine variants of HOXA1 reduces PBX1-coupled transcriptional activity and inhibits neuronal differentiationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2007Rubigilda C. Paraguison Abstract HOXA1 is a member of the homeobox gene family and is involved in early brain development. In our previous study, we identified novel variants of polyhistidine repeat tract in HOXA1 gene and showed that ectopic expression of expanded variants led to enhanced intranuclear aggregation and accelerated cell death in a time-dependent manner. Here, we further investigate the implications of polyhistidine variants on HOXA1 function. Aside from intranuclear aggregation, we observed cytosolic aggregates during the early stages of expression. Rapamycin, an autophagy inducer, resulted in decreased protein aggregation and cell death. Here, we also show an interaction between variants of HOXA1 and one of the HOX protein known cofactors, PBX1. Expanded HOXA1 variants exhibited reduced PBX1-coupled transcriptional activity through a regulatory enhancer of HOXB1. Moreover, we demonstrate that both deleted and expanded variants inhibited neurite outgrowth in retinoic acid-induced neuronal differentiation in neuroblastoma cells. These results provide further evidence that expanded polyhistidine repeats in HOXA1 enhance aggregation and cell death, resulting in impaired neuronal differentiation and cooperative binding with PBX1. © 2006 Wiley-Liss, Inc. [source] Diversity of staphylocoagulase and identification of novel variants of staphylocoagulase gene in Staphylococcus aureusMICROBIOLOGY AND IMMUNOLOGY, Issue 7 2008Marie Kinoshita ABSTRACT Staphylocoagulase (SC) is a major phenotypic determinant of Staphylococcus aureus. Serotype of SC (coagulase type) is used as an epidemiological marker and 10 types (I,X) have been discriminated so far. To clarify genetic diversity of SC within a single and among different serotype(s), we determined approximately 1500 bp-nucleotide sequences of SC gene encoding D1, D2, and central regions (N-terminal half and central regions of SC; SCNC) for a total of 33 S. aureus strains comprising two to three strains from individual coagulase types (I,VIII, X) and 10 strains which were not determined as previously known SC serotypes (ND-strains). Amino acid sequence identities of SCNC among strains with a single coagulase type of II, III, IV, V, VI and X were extremely high (more than 99%), whereas lower identity (56,87%) was observed among different types. In contrast, within a single coagulase type of I, VII, or VIII, sequence divergence was found (lowest identity; 82%). SCNC sequences from the ND-strains were discriminated into two genetic groups with an identity of 71% to each other (tentatively assigned to genotypes [XI] and [XII]), and exhibited less than 86% sequence identities to those of most known coagulase types. All the types [XI] and [XII] strains were methicillin susceptible and belonged to different sequence types from those of coagulase types I,X strains reported so far by multilocus sequence typing. These findings indicated genetic heterogeneity of SC in coagulase types I, VII, and VIII strains, and the presence of two novel SC genotypes related to antigenicity of SC serotypes. [source] Identification of five novel variants in the thiazide-sensitive NaCl co-transporter gene in Chinese patients with Gitelman syndromeNEPHROLOGY, Issue 1 2009LING QIN SUMMARY Aim: Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy characterized by hypokalaemic metabolic alkalosis, significant hypomagnesemia, low urinary calcium, secondary aldosteronism and normal blood pressure. GS is caused by inactivating variants in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl co-transporter. So far, more than 100 variants have been described in the SLC12A3 gene in Gitelman syndrome. Methods: Biochemical parameters in blood and urine were measured and documented. Genomic DNA was extracted from peripheral blood of all patients. Variants were screened for the SLC12A3 and CLCNKB gene by sequencing directly. Reverse-transcription polymerase chain reaction and complementary DNA sequence analysis were performed to confirm deletion or splicing variants. Results: We identified 13 variants in the SLC12A3 gene in 13 Chinese patients, including 10 missense substitutions, two splicing variants, and one deletion/insertion variant. Five novel variants were identified for the first time in patients with Gitelman syndrome. We did not find any variants in the CLCNKB gene. A homozygous Thr60Met carrier suffered from hypothyroidism and received thyroxine replacement therapy. Conclusion: We have identified 13 variants, including five novel variants in the SLC12A3 gene in 13 patients with Gitelman syndrome. T60M is the most frequent variant in our patients. There was no significant correlation between genotype and phenotype in our patients. [source] Association study between two variants in the DOPA decarboxylase gene in bipolar and unipolar affective disorder,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 5 2002Esther Jahnes Abstract Irregularities of dopaminergic and serotonergic neurotransmission have been implicated in a variety of neuropsychiatric disorders. DOPA decarboxylase (DDC), also known as aromatic L -amino acid decarboxylase, is an enzyme involved directly in the synthesis of dopamine and serotonin and indirectly in the synthesis of noradrenaline. Therefore, the DDC gene can be considered as a candidate gene for affective disorders. Recently, two novel variants were reported in the DDC gene: a 1-bp deletion in the promoter and a 4-bp deletion in the untranslated exon 1. Subsequently, an association case,control study including 112 English patients and 80 Danish patients with bipolar affective disorder (BPAD) revealed a significant association with the 1-bp deletion. This finding prompted us to analyze whether this effect was also present in a larger and ethnically homogeneous sample of 228 unrelated German patients with BPAD (208 patients with BP I disorder, 20 patients with BP II disorder), 183 unrelated patients with unipolar affective disorder (UPAD), and 234 healthy control subjects. For both BPAD and UPAD we could not detect a genetic association with either variant. Thus, our results do not support an involvement of the 1-bp or 4-bp deletion within the DDC gene in the etiology of affective disorders. © 2002 Wiley-Liss, Inc. [source] Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese populationCLINICAL ENDOCRINOLOGY, Issue 2 2006Rong Rong Summary Objective, Mutations in the melanocortin-4 receptor gene (MC4R) are the most common monogenic form of human obesity. However, the contribution of MC4R mutations to obesity in Chinese has not been investigated. We studied the frequency of MC4R mutations in an obese southern Chinese population and the functional consequences of the novel variants identified. Methods, We screened for MC4R mutations in 227 obese [body mass index (BMI) 35·29 ± 5·75 kg/m2] and 100 lean (BMI 21·57 ± 0·29 kg/m2) southern Chinese subjects using PCR-direct sequencing. In vitro functional studies, including cell surface expression, ligand binding, and cyclic adenosine monophosphate (cAMP) accumulation, were performed to examine the functional properties of three novel missense mutations. Results, Apart from two previously reported polymorphisms, V103I and ,176 A > C, three novel missense heterozygous variants (Y35C, C40R and M218T) were identified. The polymorphisms ,176 A > C and Y35C were detected in both obese and normal subjects with similar frequency. C40R was identified only in an obese subject. Pedigree analysis revealed M218T carriers in both lean and obese subjects. The prevalence of V103I carriers in normal-weight controls was significantly higher than that in obese subjects (5·3%vs. 1·3%, P < 0·05). In vitro functional studies showed that all three novel missense variants have normal functions. Conclusions, Two known polymorphisms and three novel variants of the MC4R were identified. No overt functional defects were observed for the three novel MC4R variants, suggesting that they might not be the cause of obesity in variant carriers. [source] | |||||||||||||