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Search Results: 1 - 10 of 1847 matches for " missense mutation "
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Abnormal gonad development in Kit W-2Bao mice caused by a Kit gene missense mutation
BaoJin Wu,LiJing Yin,ZhengLan Lu,YuShu Yin,WeiWei Yang,Rong Yang,XiaoDong Kang,GuiJie Liu,HongPing Yin,LiPing Yu,MeiEr Gu,PeiLin Wu
Chinese Science Bulletin , 2010, DOI: 10.1007/s11434-010-4219-8
Abstract: Kit W-2Bao mice are single-gene autosomal dominant mutation mice with a B6 background that were bred in our laboratory. Heterozygotes had morphological characteristics including albinism of the abdomen, extremities, and tail, whereas the homozygotes had albinism of the body, black eyes, and infertility. The homozygous mutants showed small, structurally abnormal gonads, and lacked germ cells. Heterozygous male mice lacked germ cells in some contorted seminiferous tubules. This mutation has been mapped at 43.8 cM from the centromere in chromosome 5 by linkage analysis and Kit has been identified as the candidate gene. After Kit full-length mRNA amplification, it was found that a G to T conversion at position 1228 in the ORF changed the 410th amino acid from V to F. This amino acid change could affect the protein’s secondary structure. Heterozygous mutant mice were intercrossed and homozygous mutant mice were bred and genotyped. We found that no primordial germ cells (PGCs) appeared in the urogenital ridge area at fetus day 11.5 in the homozygotes. The number of PGCs also significantly decreased in heterozygotes. At fetus day 15.5, the differentiation of the testis tubule structure was unclear; as well, they contained no spermatogonia. Female homozygotes contained no primordial follicles in the ovary. The numbers of PGCs and primordial follicles were significantly decreased in heterozygous mice. W 2Bao is the only mutated site in the extracellular 4th Ig-like domain and this mutant mouse model provides new material for the study of the mechanism of reproductive system development.
Mutación en el gen EDA1, Ala349Thr en paciente con displasia ectodérmica hipohidrótica ligada a X
Salas-Alanis,Julio C; Cepeda-Valdés,Rodrigo; González-Santos,Adriana; Amaya-Guerra,Mario; Kurban,Mazen; Christiano,Angela M;
Revista médica de Chile , 2011, DOI: 10.4067/S0034-98872011001200011
Abstract: hypohidrotic ectodermal dysplasia (hed) is a very rare disease characterized by the absence of eccrine glands, dry skin, scanty hair, and dental abnormalities. it is caused by mutations within the ed1 gene, which encodes a protein, ectodysplasin-a (eda). clinical characteristic are frontal bossing, saddle nose, pointed chin, a prominent supraorbital ridge with periorbital hyperpigmenta-tion, and anodontia. those affected show great intolerance to heat. we report the first mexican 2-year-old boy with an ala349thr missense mutation from tamaulipas, méxico.
Mutación en el gen EDA1, Ala349Thr en paciente con displasia ectodérmica hipohidrótica ligada a X Mutation in the ED1, Ala349Thr in a patient with X-linked hypohidrotic ectodermal dysplasia
Julio C Salas-Alanis,Rodrigo Cepeda-Valdés,Adriana González-Santos,Mario Amaya-Guerra
Revista médica de Chile , 2011,
Abstract: Hypohidrotic ectodermal dysplasia (HED) is a very rare disease characterized by the absence of eccrine glands, dry skin, scanty hair, and dental abnormalities. It is caused by mutations within the ED1 gene, which encodes a protein, ectodysplasin-A (EDA). Clinical characteristic are frontal bossing, saddle nose, pointed chin, a prominent supraorbital ridge with periorbital hyperpigmenta-tion, and anodontia. Those affected show great intolerance to heat. We report the first Mexican 2-year-old boy with an Ala349Thr missense mutation from Tamaulipas, México.
In silico analysis of influence of the missense mutation P629S on the molecular interaction and 3D properties of PIK3R5  [PDF]
Jameela Shinwari, Asma I. Tahir, Saeed Bohlega, Nada AlTassan
Advances in Biological Chemistry (ABC) , 2013, DOI: 10.4236/abc.2013.34044
Abstract: PIK3R5 is the regulatory subunit of Phosphoinositide 3-kinase γ (PI3Kγ) that is responsible for phosphory-lating membrane lipids to activate the AKT pathway. PIK3R5 binds Gβγ and facilitates the interaction with p110γ catalytic subunit (PIK3CG) during PI3Kγ activation. The identification of PIK3R5 P629S mutation in AOA2 patients indicated a potential defect in the AKT pathway resulting from impaired PIK3R5 interaction with Gβγ and PIK3CG, defective AKT pathway can result in cerebellar cell death causing neurological symptoms. Our in silico macromolecular docking of the wild type and mutant PIK3R5 protein models with ligand revealed an energy requirement to maintain the mutant complexes compared to no energy required to maintain the wild type complexes, in addition, the mutant structures were loose compared to rigid wild type structures, such structural changes may impair the molecular function of the PIK3R5 and hence affect the AKT pathway.
An Examination of KCNE1 Mutations and Common Variants in Chronic Tinnitus
Philipp G. Sand,Alexander Luettich,Tobias Kleinjung,Goeran Hajak,Berthold Langguth
Genes , 2010, DOI: 10.3390/genes1010023
Abstract: Chronic tinnitus is a highly prevalent and often incapacitating condition frequently associated with sensorineural hearing loss. While its etiology remains incompletely understood there is a growing awareness of genetic factors that predispose to, or aggravate chronic tinnitus. Candidate genes for the disorder include KCNE1, a potassium channel subunit gene that has been implicated in maturation defects of central vestibular neurons, in Menière's disease, and in noise-induced hearing loss. 201 Caucasian outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCNE1 open reading frame and in the adjacent sequence by direct sequencing. Allele frequencies were determined for 46 known variants, plus two novel KCNE1 mutations. These comprised one missense substitution (V47I) in the highly conserved region encoding the KCNE1 transmembrane domain, and one rare variant in the gene's 3'UTR. When genotypes were grouped assuming dominance of the minor alleles, no significant genotype or compound genotype effects were observed on tinnitus severity. The newly identified V47I substitution argues in favor of an enlarged spectrum of mutations in hearing disorders. However, with regard to allele frequencies in healthy control populations from earlier studies, more common KCNE1 variants are unlikely to play a major role in chronic tinnitus. Further investigations are invited to address variation in additional channel subunits as possible risk factors in tinnitus.
Computational analysis of deleterious missense mutations in aspartoacylase that cause Canavan’s disease
K. Sreevishnupriya,P. Chandrasekaran,A. Senthilkumar,R. Sethumadhavan,V. Shanthi,P. Daisy,J. Nisha,K. Ramanathan,R. Rajasekaran
Science China Life Sciences , 2012, DOI: 10.1007/s11427-012-4406-8
Abstract: In this work, the most detrimental missense mutations of aspartoacylase that cause Canavan’s disease were identified computationally and the substrate binding efficiencies of those missense mutations were analyzed. Out of 30 missense mutations, I-Mutant 2.0, SIFT and PolyPhen programs identified 22 variants that were less stable, deleterious and damaging respectively. Subsequently, modeling of these 22 variants was performed to understand the change in their conformations with respect to the native aspartoacylase by computing their root mean squared deviation (RMSD). Furthermore, the native protein and the 22 mutants were docked with the substrate NAA (N-Acetyl-Aspartic acid) to explain the substrate binding efficiencies of those detrimental missense mutations. Among the 22 mutants, the docking studies identified that 15 mutants caused lower binding affinity for NAA than the native protein. Finally, normal mode analysis determined that the loss of binding affinity of these 15 mutants was caused by altered flexibility in the amino acids that bind to NAA compared with the native protein. Thus, the present study showed that the majority of the substrate-binding amino acids in those 15 mutants displayed loss of flexibility, which could be the theoretical explanation of decreased binding affinity between the mutant aspartoacylases and NAA.
Identification of a Novel Missense Mutation in Exon 4 of the Human Factor VIII Gene Associated with Sever Hemophilia a Patient
Habib Onsori,Mohammad Ali Hosseinpour,Sheideh Montaser-Kouhsari,Mohammad Asgharzadeh
Pakistan Journal of Biological Sciences , 2007,
Abstract: Hemophilia A is an X-linked congenital bleeding disorder caused by factor VIII deficiency. The factor VIII gene is on the long arm of the X chromosome at Xq28 spans 186 kb and consists of 26 exons. In this study to identify defects in the factor VIII gene, Single-Stranded Conformation Polymorphism (SSCP) analysis was used. A novel missense mutation due to T → C transition at codon 153 (TGC) of the factor VIII gene which replace a cysteine with an arginine residue, was found in a patient of North-Western of Iran with sever hemophilia A. Direct sequencing of the amplified fragment was performed to confirm the mutation. This study shows that we can use of Polymerase Chain Reaction (PCR) and silver staining of SSCP methods for detecting most of the point mutations causative hemophilia A.
Vladimir Margeta,Laura Vargovi?,Gordana Kralik,Goran Ku?ec
Poljoprivreda (Osijek) , 2009,
Abstract: The aim of the research was to determine the influence of polymorphism in MC4R genes on slaughtering traits. The research was carried out on 60 crossbreeds of Large White and German Landrace in the dam line and of Duroc in the sire line. According to tests performed, it was determined that polymorphism in MC4R genes affected some quantitative traits of pigs related to feed intake, like MLD thickness, electric conductivity and meat color. Presented results of the examined slaughtering traits pointed out the need for further research in order to obtain more realistic relation of polymorphism in MC4R genes and slaughtering traits. It is also important to increase the number of pigs under research, as 60 pigs are a relatively small number for such research. Furthermore, other pig breeds should be involved in the research aiming to examine connection of polymorphism in MC4R genes with slaughtering traits within one particular breed, especially if it is known that polymorphism in MC4R genes affects slaughtering traits in different ways, depending on the examined breed.
Targeted capture and massively parallel sequencing in pediatric cardiomyopathy: development of novel diagnostics
Muhammad Tariq,Thanh-Tam Le,Patrick Putnam,Steven Kindel
Cardiogenetics , 2012, DOI: 10.4081/236
Abstract: Pediatric cardiomyopathy is a genetically heterogeneous disease associated with significant morbidity. Although identification of underlying etiology is important for management, therapy, and screening at risk family members, molecular diagnosis is difficult due to the large number of causative genes, high rate of private mutations, and cost. We aimed to define the genetic basis of pediatric cardiomyopathy and test a novel diagnostic tool using a custom targeted microarray coupled to massively parallel sequencing. Three patients with cardiomyopathy were screened using a custom NimbleGen sequence capture array containing 110 genes and providing 99.9% coverage of the exons of interest. The sensitivity and specificity was >99% as determined by comparison to long range PCR-based massively parallel sequencing, Sanger sequencing of missense variants, and SNP genotyping using the Illumina Infinium Omni1 array. Overall, 99.73% of the targeted regions were captured and sequenced at >10X coverage, allowing reliable mutation calling in all patients. Analysis identified a total of 165 non-synonymous coding single nucleotide polymorphisms (cSNPs), of which 89 were unique and 14 were novel. On average, each patient had 4 cSNPs predicted to be pathogenic. We report a cardiomyopathy sequencing array that allows simultaneous assessment of 110 genes. Comparison of targeted sequence capture vs. PCR-based enrichment methods demonstrates that the former is more sensitive and efficient. Array-based sequence capture technology followed by massively parallel sequencing is promising as a robust and comprehensive tool for genetic screening of cardiomyopathy. These results provide important information about genetic architecture and indicate that improved annotation of variants and interpretation of clinical significance, particularly in cases with multiple rare variants, are important for clinical utility.
Functional Analysis of Familial Asp67Glu and Thr1051Ser BRCA1 Mutations in Breast/Ovarian Carcinogenesis
Malinee Pongsavee,Pimpicha Patmasiriwat,Grady F. Saunders
International Journal of Molecular Sciences , 2009, DOI: 10.3390/ijms10094187
Abstract: Estrogen is believed to be pre-initiator in the risk of breast cancer. The BRCA1 is a tumor suppressor gene associated with breast and ovarian cancer risk. This report describes functional analysis of two BRCA1 missense mutations (Asp67Glu and Thr1051Ser) observed in the familial breast/ovarian cancer patients in Thailand. Levels of luciferase activity of the two mutations were relatively lower than in the wild-type BRCA1. It is indicated that mutants may fail to promote the estrogen receptor dependent functions.It is presumed that estrogen and insulin/IGF-1 regulate c-Myc and cyclin D1 during breast cancer cell proliferation. It is also likely to affect ubiquitination mechanism. Since three affected cancer families carry the Asp67Glu mutation, it is believed that this type of mutation could have some effect on breast/ovarian cancer progression.
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