Coding Region of IRF6 Gene May Not Be Causal for Van Der Woude Syndrome in Cases from India

2009 ◽  
Vol 46 (5) ◽  
pp. 541-544 ◽  
Author(s):  
Akhtar Ali ◽  
Subodh Kumar Singh ◽  
Rajiva Raman
Keyword(s):  
Present Report ◽  
Direct Sequencing ◽  
Geographical Area ◽  
Point Mutations ◽  
Coding Region ◽  
Van Der Woude Syndrome ◽  
Coding Regions ◽  
Irf6 Gene ◽  
Novel Variants ◽  
History Of

Objective: Evaluation of the IRF6 gene in Van der Woude syndrome cases from an Indian population. Subjects: Nine affected and four unaffected individuals from seven families with Van der Woude syndrome as well as five normal controls (with no history of Van der Woude or any other congenital malformation and belonging to the same geographical area as the families with Van der Woude syndrome). Method: Direct sequencing of all coding regions and exon-intron boundaries of the IRF6 gene. Results: Five novel variants: IVS1+3900 A>G, 191 T>C, IVS4+775 C>T, IVS8+218 C>T, 1511 T>A (Ser 416 Arg) and two known variants: IVS6+27 C>G, 1083 G>A (V274I) were detected. Except for one, all were in noncoding regions either in 3′UTR or in introns. There was only one mutation in the coding region, detected in a normal control. Conclusion: The present report indicates that point mutations in the coding region of the IRF6 gene may not be a major cause of Van der Woude syndrome in Indian populations.

A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis

Blood ◽  
1996 ◽  
Vol 88 (10) ◽  
pp. 3698-3703 ◽  
Author(s):  
SR Poort ◽  
FR Rosendaal ◽  
PH Reitsma ◽  
RM Bertina
Keyword(s):  
Confidence Interval ◽  
Venous Thrombosis ◽  
Case Control Study ◽  
Direct Sequencing ◽  
Population Based ◽  
Coding Regions ◽  
History Of ◽  
Prothrombin Gene ◽  
Polymerase Chain ◽  
Control Study

We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia. All the exons and the 5′- and 3′-UT region of the prothrombin gene were analyzed by polymerase chain reaction and direct sequencing in 28 probands. Except for known polymorphic sites, no deviations were found in the coding regions and the 5′-UT region. Only one nucleotide change (a G to A transition) at position 20210 was identified in the sequence of the 3′-UT region. Eighteen percent of the patients had the 20210 AG genotype, as compared with 1% of a group of healthy controls (100 subjects). In a population-based case-control study, the 20210 A allele was identified as a common allele (allele frequency, 1.2%; 95% confidence interval, 0.5% to 1.8%), which increased the risk of venous thrombosis almost threefold odds ratio, 2.8; 95% confidence interval, 1.4 to 5.6. The risk of thrombosis increased for all ages and both sexes. An association was found between the presence of the 20210 A allele and elevated prothrombin levels. Most individuals (87%) with the 20210 A allele are in the highest quartile of plasma prothrombin levels (> 1.15 U/mL). Elevated prothrombin itself also was found to be a risk factor for venous thrombosis.

scholarly journals Boundaries of somatic mutation in rearranged immunoglobulin genes: 5' boundary is near the promoter, and 3' boundary is approximately 1 kb from V(D)J gene.

1990 ◽  
Vol 172 (6) ◽  
pp. 1717-1727 ◽  
Author(s):  
S G Lebecque ◽  
P J Gearhart
Keyword(s):  
Structural Information ◽  
Gene Segment ◽  
Point Mutations ◽  
Sequence Motif ◽  
Immunoglobulin Gene ◽  
Coding Region ◽  
Nucleotide Substitutions ◽  
Coding Regions ◽  
Dna Strands ◽  
Transcriptional State

To investigate why somatic mutations are spatially restricted to a region around the rearranged V(D)J immunoglobulin gene, we compared the distribution of mutations flanking murine V gene segments that had rearranged next to either proximal or distal J gene segments. 124 nucleotide substitutions, nine deletions, and two insertions were identified in 32,481 bp of DNA flanking the coding regions from 17 heavy and kappa light chain genes. Most of the mutations occurred within a 2-kb region centered around the V(D)J gene, regardless of which J gene segment was used, suggesting that the structural information for mutation is located in sequences around and within the V(D)J gene, and not in sequences downstream of the J gene segments. The majority of mutations were found within 300 bp of DNA flanking the 5' side of the V(D)J gene and 850 bp flanking the 3' side at a frequency of 0.8%, which was similar to the frequency in the coding region. The frequency of flanking mutations decreased as a function of distance from the gene. There was no evidence for hot spots in that every mutation was unique and occurred at a different position. No mutations were found upstream of the promoter region, suggesting that the promoter delimits a 5' boundary, which provides strong evidence that transcription is necessary to generate mutation. The 3' boundary was approximately 1 kb from the V(D)J gene and was not associated with a DNA sequence motif. Occasional mutations were located in the nuclear matrix association and enhancer regions. The pattern of substitutions suggests that there is discrimination between the two DNA strands during mutation, in that the four bases were mutated with different frequencies on each strand. The high frequency of mutations in the 3' flanking region and the uniqueness of each mutation argues against templated gene conversion as a mechanism for generating somatic diversity in murine V(D)J genes. Rather, the data support a model for random point mutations where the mechanism is linked to the transcriptional state of the gene.

scholarly journals Recurrent deletion in the human antithrombin III gene

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 1027-1032
Author(s):  
CB Grundy ◽  
F Thomas ◽  
DS Millar ◽  
M Krawczak ◽  
E Melissari ◽  
...  
Keyword(s):  
Antithrombin Iii ◽  
Direct Sequencing ◽  
Consensus Sequence ◽  
Type I ◽  
Coding Regions ◽  
Human Genes ◽  
History Of ◽  
Polymerase Chain ◽  
Gene Exon ◽  
Recurrent Deletion

Eight unrelated patients with recurrent thromboembolism, a family history of thrombosis, and plasma antithrombin III (ATIII) activity/antigen levels consistent with a diagnosis of heterozygous type I ATIII deficiency were studied by polymerase chain reaction/direct sequencing of ATIII gene exon-coding regions. Frameshift mutations of one base and two bases, respectively, were found to have occurred in two unrelated patients at the same GAG codon (Glu 245) within exon 4 of the ATIII gene. A literature search showed six further hitherto unrecognized deletion “hotspots” in four other human genes. These deletion-prone sites exhibited sufficient sequence homology with each other to derive a consensus sequence (T G A/G A/G G A/C), suggesting that deletion in human genes may not only be non- random but also sequence-directed.

scholarly journals SignalsThat Dictate Nuclear Localization of Human Papillomavirus Type 16Oncoprotein E6 in LivingCells

2003 ◽  
Vol 77 (24) ◽  
pp. 13232-13247 ◽  
Author(s):  
Mingfang Tao ◽  
Michael Kruhlak ◽  
Shuhua Xia ◽  
Elliot Androphy ◽  
Zhi-Ming Zheng
Keyword(s):  
Human Papillomavirus ◽  
Nuclear Localization ◽  
Nuclear Import ◽  
Nuclear Protein ◽  
Fluorescent Protein ◽  
Present Report ◽  
Cell Cycle Control ◽  
Point Mutations ◽  
Coding Region ◽  
Nuclear Localization Signals

ABSTRACT Human papillomavirus (HPV) type 16 E6 (16E6) is an oncogenic, multifunctional nuclear protein that induces p53 degradation and perturbs normal cell cycle control, leading to immortalization and transformation of infected keratinocytes and epithelial cells. Although it is unclear how 16E6 disrupts the epigenetic profile of host genes, its presence in the nucleus is a key feature. The present report describes intrinsic properties of 16E6 that influence its nuclear import in living cells. When the coding region of full-length 16E6 was inserted in frame into the C terminus of green fluorescent protein (GFP), it effectively prevented the 16E6 pre-mRNA from being spliced and led to the expression of a GFP-E6 fusion which localized predominantly to the nucleus. Further studies identified three novel nuclear localization signals (NLSs) in 16E6 that drive the protein to accumulate in the nucleus. We found that all three NLS sequences are rich in positively charged basic residues and that point mutations in these key residues could abolish the retention of 16E6 in the nucleus as well as the p53 degradation and cell immortalization activities of the protein. When inserted into corresponding regions of low-risk HPV type 6 E6, the three NLS sequences described for 16E6 functioned actively in converting the normally cytoplasmic HPV type 6 E6 into a nuclear protein. The separate NLS sequences, however, appear to play different roles in nuclear import and retention of HPV E6. The discovery of three unique NLS sequences in 16E6 provides new insights into the nuclear association of 16E6 which may reveal other novel activities of this important oncogenic protein.

scholarly journals Recurrent deletion in the human antithrombin III gene

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 1027-1032 ◽  
Author(s):  
CB Grundy ◽  
F Thomas ◽  
DS Millar ◽  
M Krawczak ◽  
E Melissari ◽  
...  
Keyword(s):  
Antithrombin Iii ◽  
Direct Sequencing ◽  
Consensus Sequence ◽  
Type I ◽  
Coding Regions ◽  
Human Genes ◽  
History Of ◽  
Polymerase Chain ◽  
Gene Exon ◽  
Recurrent Deletion

Abstract Eight unrelated patients with recurrent thromboembolism, a family history of thrombosis, and plasma antithrombin III (ATIII) activity/antigen levels consistent with a diagnosis of heterozygous type I ATIII deficiency were studied by polymerase chain reaction/direct sequencing of ATIII gene exon-coding regions. Frameshift mutations of one base and two bases, respectively, were found to have occurred in two unrelated patients at the same GAG codon (Glu 245) within exon 4 of the ATIII gene. A literature search showed six further hitherto unrecognized deletion “hotspots” in four other human genes. These deletion-prone sites exhibited sufficient sequence homology with each other to derive a consensus sequence (T G A/G A/G G A/C), suggesting that deletion in human genes may not only be non- random but also sequence-directed.

scholarly journals A Case of Manifesting Carrier with DMD Phenotype

2009 ◽  
Vol 52 (4) ◽  
pp. 167-170 ◽  
Author(s):  
Akshay Anand ◽  
Monika Vinish ◽  
Sudesh Prabhakar
Keyword(s):  
Polymerase Chain Reaction ◽  
Direct Sequencing ◽  
Point Mutations ◽  
Single Strand Conformation Polymorphism ◽  
Clinical Findings ◽  
Lower Limbs ◽  
Chain Reaction ◽  
History Of ◽  
Polymerase Chain ◽  
Conformation Polymorphism

A case of a 35-year old female with a history of proximal weakness in lower limbs and bulkiness of both calves manifesting before ten years of age was reported. Clinical findings were suggestive of muscular dystrophy. Genetic analysis using polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) and direct sequencing revealed several point mutations, which account for dystrophin dysfunction and DMD type pathogenesis.

Characterisation of 96 mutations in 128 unrelated severe haemophilia A patients from France

2006 ◽  
Vol 95 (04) ◽  
pp. 593-599 ◽  
Author(s):  
Christine Vinciguerra ◽  
Christophe Zawadzki ◽  
Yesim Dargaud ◽  
Gilles Pernod ◽  
Claire Berger ◽  
...  
Keyword(s):  
Factor Viii ◽  
Direct Sequencing ◽  
Point Mutations ◽  
Haemophilia A ◽  
Missense Mutations ◽  
Severe Haemophilia ◽  
Coding Region ◽  
Nucleotide Substitutions ◽  
Large Deletions ◽  
Fviii Inhibitor

SummaryDirect sequencing of the coding region of factor VIII (F8) gene was used to determine the mutations responsible for severe haemophilia A (FVIII<1%) in 128 unrelated haemophiliacs A, negative for intron 22 and intron 1 inversions. A mutation was found in 122/128 patients (95%). Ninety-six distinct mutations were identified in this cohort, 62 of these are novel. They consisted of deletions (7 large and 24 small deletions), insertions (n=9), associations of insertion/deletion (n=2), association of deletion/substitution (n=1), and single nucleotide substitutions (53 point mutations consisting of 31 missense, 20 nonsense, and 2 splicing mutations). Twenty-two patients had developed inhibitors, and among this subgroup 3 large deletions, 6 frameshift, 9 nonsense and 4 missense mutations were detected. For6 patients, among which one developed an anti-FVIII inhibitor, no mutations were detected in the coding and splicing regions of factor VIII gene. Different approaches of molecular modelling were performed in addition to familial linkage analysis to determine the pathophysiological responsibility of these novel missense mutations.

scholarly journals Molecular basis of familial adenomatous polyposis in the southeast of Brazil: identification of six novel mutations

2019 ◽  
Vol 34 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Luiza Ferreira Araujo ◽  
Greice Andreotti Molfetta ◽  
Otavio Costa Vincenzi ◽  
Jair Huber ◽  
Lorena Alves Teixeira ◽  
...  
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Direct Sequencing ◽  
Point Mutations ◽  
Adenomatous Polyposis ◽  
Novel Mutations ◽  
Coding Regions ◽  
Extracolonic Manifestations ◽  
Mutyh Gene ◽  
Different Populations ◽  
Dependent Probe

Background: The goal of this study was to screen point mutations and deletions in APC and MUTYH genes in patients suspected of familial adenomatous polyposis (FAP) in a Brazilian cohort. Methods: We used high-resolution melting, Sanger direct sequencing and multiplex ligation-dependent probe association (MLPA) assays to identify point mutations, and large genomic variations within the coding regions of APC and MUTYH genes. Results: We identified 19 causative mutations in 40 Brazilian patients from 20 different families. Four novel mutations were identified in the APC gene and two in the MUTYH gene. We also found a high intra- and inter-familial diversity regarding extracolonic manifestations, and gastric polyps were the most common manifestation found in our cohort. Conclusion: We believe that the FAP mutational spectrum can be population-specific and screening FAP patients in different populations can improve pre-clinical diagnosis and improve clinical conduct.

scholarly journals Mouse synexin (annexin VII) polymorphisms and a phylogenetic comparison with other synexins

1993 ◽  
Vol 289 (3) ◽  
pp. 735-741 ◽  
Author(s):  
Z Y Zhang-Keck ◽  
A L Burns ◽  
H B Pollard
Keyword(s):  
Amino Acid ◽  
Blot Analysis ◽  
Mouse Liver ◽  
Point Mutations ◽  
Coding Region ◽  
Alpha Helices ◽  
Coding Regions ◽  
Terminal Domain ◽  
Group I ◽  
Group Ii

Two sets of cDNAs encoding mouse synexin were isolated from a liver cDNA library and sequenced. The coding regions of synexin clones show 99% identity. By contrast, the two mouse synexin cDNAs differ in a number of ways in both 5′ and 3′ non-coding regions. The two sets of cDNA encode a polypeptide of 463 amino acid residues which has a deduced molecular mass of 50 kDa. The amino acid sequence of mouse synexin shows a high degree of similarity to both the unique N-terminal domain and the highly conserved C-terminal domain of previously cloned human synexin. Northern-blot analysis using mouse liver polyadenylated RNA revealed two transcripts of 1.8 kb and 2.6 kb, corresponding to group I and group II respectively. Further hybridization analysis using specific sequences from each set of clones showed that the two sizes of mRNAs differ in the length of the 3′ non-coding region which corresponded to the cDNAs. Both mouse liver synexin and recombinant mouse synexin expressed in Escherichia coli reacted after Western-blot analysis with a goat antibody against bovine synexin. Only in the larger group-II cDNAs do we find point mutations leading to amino acid replacements of Ser to Ala at residue 145 in the unique N-terminal domain, and of Ala to Gly at residue 304 in the transition zone between repeats II and III. We conclude from a comparison of mouse, human and Dictyostelium synexins that changes occur predominantly in the hydrophobic N-terminal domain, or, in the C-terminal region at the ends of some predicted alpha-helices, on the hydrophobic face of the amphipathic C-helices, and within a lengthy non-helical domain connecting major repeats II and III.

scholarly journals Evaluation of variations in plastid DNA non-coding regions in selected species of the genus Solanum

2017 ◽  
Vol 53 (No. 3) ◽  
pp. 127-131
Author(s):  
V. Sedláková ◽  
P. Sedlák ◽  
D. Zeka ◽  
J. Domkářová ◽  
P. Doležal ◽  
...  
Keyword(s):  
Denaturing Gradient Gel Electrophoresis ◽  
Direct Sequencing ◽  
Single Point ◽  
Point Mutations ◽  
Plastid Dna ◽  
Intraspecific Diversity ◽  
Trnl Intron ◽  
Coding Regions ◽  
Gradient Gel Electrophoresis ◽  
Single Point Mutations

The diversity of three non-coding plastid DNA loci (trnL/trnF spacer, trnV/16SrRNA spacer, trnL/trnL intron) was assessed in 16 Solanum L. species (135 individuals). Polymorphisms were detected by denaturing gradient gel electrophoresis (DGGE) and verified by direct sequencing. No intraspecific diversity and only poor interspecific diversity was detected. Unique S. mochiquense Ochoa specific length polymorphism at the trnL/trnL locus represented by duplication of an 18 bp segment was discovered. The detected DGGE interspecific trnL/trnF locus polymorphism did not specifically associate with single point mutations in the sequence confirmed by sequencing. The DGGE method was found to be a simple and cheap pre-exploring tool for mutation detection in compared DNA regions. Some identified polymorphisms can be used in the management of genetic resources.

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