共查询到20条相似文献,搜索用时 31 毫秒
1.
Joachim Hundrieser Silvia Bremer Frank Peinemann Manfred Stuhrmann Nicola Hoffknecht Brigitte Wulf Jörg Schmidtke Jochen Reiss Günter Maaß Burkhard Tümmler 《Human genetics》1990,85(4):409-410
Summary The F508 deletion in the cystic fibrosis transmembrane conductance regulator (CFTR) gene was found in 8 out of 30 Turkish
cystic fibrosis (CF) chromosomes (27%). Five Turkish ΔF508 CF chromosomes were associated with the risk haplotype B in KM19
(2 allele)/XV2c (1 allele). In the Turkish population, cystic fibrosis is predominantly caused by mutations other than the
F508 deletion. 相似文献
2.
The spectrum of cystic fibrosis (CF) mutations in the North African population remains poorly known. In order to offer an effective diagnostic service and to determine accurate risk estimates, we decided to identify the CF mutations in 10 Algerian CF families. We carried out a chemical-clamp denaturing gradient gel electrophoresis analysis of the CFTR gene and automated direct DNA sequencing. We identified 5 mutations and we characterized 60% of the CF chromosomes. Taking advantage of the homogeneity of the sample, we report clinical features of homozygous CF patients. 相似文献
3.
van de Vosse E Ali S de Visser AW Surjadi C Widjaja S Vollaard AM van Dissel JT 《Human genetics》2005,118(1):138-140
The cystic fibrosis transmembrane conductance regulator (CFTR) is the affected protein in cystic fibrosis (CF). The high rate of CF carriers has led to speculation that there must be, similar to the sickle cell haemoglobin advantage in malaria, a selective advantage for heterozygotes. Such a selective advantage may be conferred through reduced attachment of Salmonella typhi to intestinal mucosa, thus providing resistance to typhoid fever. We tested this hypothesis by genotyping patients and controls in a typhoid endemic area in Indonesia for two highly polymorphic markers in CFTR and the most common CF mutation. We found an association between genotypes in CFTR and susceptibility to typhoid fever (OR=2.6). These analyses suggest that the role CFTR plays in vitro in S. typhi infection is also important for infection in the human population.Electronic Supplementary Material Supplementary material is available for this article at 相似文献
4.
B. Bramanti L. Sineo M. Vianello D. Caramelli S. Hummel B. Chiarelli B. Herrmann 《International Journal of Anthropology》2000,15(3-4):255-262
Recently a heterozygote advantage was suggested to explain the high incidence (1:25 carrier individuals in Europeans) of the
cystic fibrosis gene. This selective advantage was speculated to be due to a high resistance to chloride-secreting diarrhea,
including cholera. Up to now the major efforts to test directly this hypothesis have been limited to animal models.
We propose to verify the hypothesis directly on a sample of human individuals who died from cholera during the epidemic in
the Mediterranean basin at the beginning of the nineteenth century. In this preliminary investigation we have attempted to
check for the presence of amplifiable DNA in the human remains simultaneously in terms of genetic fingerprints and for cystic
fibrosis mutations. 相似文献
5.
M Modell 《BMJ (Clinical research ed.)》1993,307(6908):849-852
The identification of the gene for cystic fibrosis has led to the possibility of population based screening for carriers of cystic fibrosis to identify couples at risk of having an affected child. Pilot studies have shown that screening is feasible and does not cause untoward anxiety, though the uptake of testing varies considerably with the setting and method of invitation. Screening offered at times when individuals (and health professionals) perceive it as directly relevant will probably gradually become established in the United Kingdom. This review examines the role of general practice in genetic carrier screening as exemplified by cystic fibrosis. General practice has a pivotal role from the beginning in providing individuals and couples with information, facilitating testing of patients'' relatives and of carriers identified by screening elsewhere (such as antenatal clinics), and offering testing in the context of reproduction. Screening for the cystic fibrosis gene will probably be followed by other genetic screening programmes. 相似文献
6.
Summary Three independent observers assessed the discriminating power of serum isoelectric focusing in detecting the presence of the cystic fibrosis gene. On the basis of average scores, four out of 23 cystic fibrosis patients, six out of 22 heterozygotes, and three out of 16 controls were misclassified. However, the mean scores for the cystic fibrosis and heterozygote groups were significantly different to that for the control group. It is concluded that isoelectric focusing is insufficiently reliable to be used for diagnosis or heterozygote detection in cystic fibrosis, but that it does provide evidence for the presence of a protein associated with the mutant gene. 相似文献
7.
André Reis Silvia Bremer Manfred Schlösser Margarete Dueck Ingolf Böhm Joachim Hundrieser Milan Macek Manfred Stuhrmann Michael Wagners Thilo Dörk Frank Schnieders Hans-Georg Posselt Ulrich Wahn Jochen Reisse Friedrich K. Trefz Burkhard Tümmler Michael Krawczak Jörg Schmidtke 《Human genetics》1990,85(4):421-422
Summary We have measured the frequency of the ΔF508 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
and its association with cystic fibrosis (CF)-linked marker haplotypes in the German population. Based on the analysis of
400 CF chromosomes, the frequency of the ΔF508 mutation is estimated to be 77.3%, the vast majority being associated with
marker haplotype KM19-XV2c 2 1. Our data further suggest the presence of another frequent CF mutation associated with this
marker haplotype. 相似文献
8.
Cloning the mouse homolog of the human cystic fibrosis transmembrane conductance regulator gene. 总被引:14,自引:0,他引:14
F Tata P Stanier C Wicking S Halford H Kruyer N J Lench P J Scambler C Hansen J C Braman R Williamson 《Genomics》1991,10(2):301-307
The cystic fibrosis transmembrane conductance regulator is encoded by the gene known to be mutated in patients with cystic fibrosis. This paper reports the cloning and sequencing of cDNAs for the murine homolog of the human cystic fibrosis transmembrane conductance regulator gene. A clone that, by analogy to the human sequence, extends 3' from exon 9 to the poly(A) tail was isolated from a mouse lung cDNA library. cDNA clones containing exons 4 and 6b were also isolated and sequenced, but the remainder of the mRNA proved difficult to obtain by conventional cDNA library screening. Sequences spanning exons 1-9 were cloned by PCR from mouse RNA. The deduced mouse protein sequence is 78% identical to the human cystic fibrosis transmembrane regulator, with higher conservation in the transmembrane and nucleotide-binding domains. Amino acid sequences in which known cystic fibrosis missense mutations occur are conserved between man and mouse; in particular, the predicted mouse protein has a phenylalanine residue corresponding to that deleted in the most common human cystic fibrosis mutation (delta F508), which should allow the use of transgenic strategies to introduce this mutation in attempts to create a "cystic fibrosis mouse". 相似文献
9.
A. A. Stepanova A. V. Abrukova E. N. Savaskina A. V. Polyakov 《Russian Journal of Genetics》2012,48(7):731-737
Molecular genetic study of the CFTR gene in cystic fibrosis patients from the Chuvash Republic is presented. We found linkage disequilibrium of the disease with 22-7-16-13 haplotype using intragenic markers. Major mutation p.E92K was revealed in chromosomes carrying this haplotype. The frequency of this mutation in Chuvash patients was 66.6%. Population study of the distribution of two mutations (p.E92K and F508del) of the CFTR gene revealed that their population frequency in heterozygous carriers was one per 37 subjects while calculated cystic fibrosis frequency in Chuvashia is one per 5420 newborns. 相似文献
10.
E. Ranieri B. D. Lewis R. L. Gerace R. G. Ryall C. P. Morris P. V. Nelson W. F. Carey E. F. Robertson 《BMJ (Clinical research ed.)》1994,308(6942):1469-1472
OBJECTIVE--To assess the performance and impact of a two tier neonatal screening programme for cystic fibrosis based on an initial estimation of immunoreactive trypsinogen followed by direct gene analysis. DESIGN--Four year prospective study of two tier screening strategy. First tier: immunoreactive trypsinogen measured in dried blood spot samples from neonates aged 3-5 days. Second tier: direct gene analysis of cystic fibrosis mutations (delta F508, delta I506, G551D, G542X, and R553X) in samples with immunoreactive trypsinogen concentrations in highest 1% and in all neonates with meconium ileus or family history of cystic fibrosis. SETTING--South Australian Neonatal Screening Programme, Adelaide. SUBJECTS--All 88,752 neonates born in South Australia between December 1989 and December 1993. INTERVENTIONS--Neonates with two identifiable mutations were referred directly for clinical assessment and confirmatory sweat test; infants with only one identifiable mutation were recalled for sweat test at age 3-4 weeks. Parents of neonates identified as carriers of cystic fibrosis mutation were counselled and offered genetic testing. MAIN OUTCOME MEASURES--Identification of all children with cystic fibrosis in the screened population. RESULTS--Of 1004 (1.13%) neonates with immunoreactive trypsinogen > or = 99th centile, 912 (90.8%) had no identifiable mutation. 23 neonates were homozygotes or compound heterozygotes; 69 carried one identifiable mutation, of whom six had positive sweat tests. Median age at clinical assessment for the 29 neonates with cystic fibrosis was 3 weeks; six had meconium ileus and two had affected siblings. 63 neonates were identified as carriers of a cystic fibrosis mutation. Extra laboratory costs for measuring immunoreactive trypsinogen and direct gene analysis were $A1.50 per neonate screened. CONCLUSION--This strategy results in early and accurate diagnosis of cystic fibrosis and performs better than screening strategies based on immunoreactive trypsinogen measurement alone. 相似文献
11.
Livshyts' LA 《T?Sitologii?a i genetika》2000,34(4):6-9
The results of DNA analysis of major mutations in CFTR gene in 260 families from Ukraine with high risk of cystic fibrosis are presented. The perspectives of molecular diagnosis as a main tool for cystic fibrosis prevention are discussed. 相似文献
12.
Pascal Barbry Brigitte Simon-Bouy Marie-Geneviève Mattéi Eric Le Guern Bartolomé Jaume-Roig Olivier Chassande Axel Ullrich Michel Lazdunski 《Human genetics》1990,85(6):587-589
Summary The apical sodium channel is essential for sodium reabsorption by the kidney. Its activity is blocked by the diuretic amiloride. Using a human cDNA coding for the amiloride binding protein (ABP), the corresponding structural gene was mapped to human chromosome 7q34–q36 by in situ hybridization. This region flanks the region implicated in cystic fibrosis (7q32). Because an alteration of the amiloride sensitive sodium channel function has been suggested in cystic fibrosis, a possible link between the ABP gene and this disease was analyzed by restriction fragments length polymorphism (RFLP) analyses. From this study, it appears that the gene coding for ABP is not directly modified by mutations causing cystic fibrosis. 相似文献
13.
Becker KA Tümmler B Gulbins E Grassmé H 《Biochemical and biophysical research communications》2010,403(3-4):368-374
Cystic fibrosis is a hereditary metabolic disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and characterized by severe intestinal and pulmonary symptoms, in particular intestinal obstruction, pancreatic insufficiency, chronic pulmonary inflammation, and microbial lung infections. Recent studies have demonstrated an accumulation of ceramide in the lungs of cystic fibrosis patients and in several mouse models. These findings showed that pulmonary ceramide concentrations play an important role in pulmonary inflammation and infection. In this study we investigated whether ceramide concentrations are also altered in the trachea and the intestine of cystic fibrosis mice and whether an accumulation of ceramide in these organs has functional consequences that are typical of cystic fibrosis. Our findings demonstrate a marked accumulation of ceramide in tracheal and intestinal epithelial cells of cystic fibrosis mice. When acid sphingomyelinase activity is inhibited by treating cystic fibrosis mice with amitriptyline or by genetic heterozygosity of acid sphingomyelinase in cystic fibrosis mice, ceramide concentrations in the trachea and the intestine are normalized. Moreover, increased rates of cell death and increased cytokine concentrations in the trachea, the intestine, or both were normalized by the inhibition of acid sphingomyelinase activity and the concomitant normalization of ceramide concentrations. These findings suggest that ceramide plays a crucial role in inflammation and increased rates of cell death in several organs of cystic fibrosis mice. 相似文献
14.
Cystic fibrosis is a common, fatal disorder caused by abnormalities in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR encodes a chloride channel that regulates secretion in many exocrine tissues. The presentation of cystic fibrosis is highly variable as measured by the age of onset of disease, the presence of pancreatic insufficiency, or the progression of lung disease. Over 400 mutations in the CFTR gene have been described in cystic fibrosis patients and considerable effort has focused on the correlation between specific mutations and genotypes and clinical characteristics. Individual tissues display variation in their sensitivity to CFTR mutations. The vas deferens is functionally disrupted in nearly all males, whereas mild and severe pancreatic involvement is determined by the patient's genotype. The severity of pulmonary disease is poorly correlated with genotype, suggesting that there are other important genetic and/or environmental factors that contribute to lung infections and the subsequent disruption of lung function. 相似文献
15.
Chatellier J Hartley O Griffiths AD Fersht AR Winter G Riechmann L 《FEBS letters》1999,452(3):371-374
A number of disorders related to cystic fibrosis have been described since the cloning of the cystic fibrosis gene, including infertility due to the congenital bilateral absence of the vas deferens. We have identified, in several patients, complex cystic fibrosis transmembrane conductance regulator genotypes like double-mutant alleles. We have now analyzed the structure-function relationships of one of these mutants, R74W-D1270N cystic fibrosis transmembrane conductance regulator, expressed in HeLa cells, to evaluate the contribution of each mutation in the phenotype. We found that R74W cystic fibrosis transmembrane conductance regulator appears to be a polymorphism, while D1270N cystic fibrosis transmembrane conductance regulator could be responsible for the congenital bilateral absence of the vas deferens phenotype. The combination of the two produced a more severe effect on the chloride conductance pathway as well as on the phenotype. 相似文献
16.
OBJECTIVE--To obtain information about social and demographic characteristics and lifestyle of adult patients with cystic fibrosis, including those who do not attend major specialist clinics. DESIGN--Confidential self completion postal questionnaire to adult patients with cystic fibrosis, asking about social and demographic characteristics, social class and occupation, employment, education, insurance and social security benefits, symptom severity, and medical care. SETTING--National association for adults with cystic fibrosis. SUBJECTS--1052 adult members of the Association of Cystic Fibrosis Adults UK, accounting for 68% of those with cystic fibrosis in the United Kingdom population over 16 years of age and over 80% of those over 25 in June 1990. RESULTS--The response rate was 82% (397 women, 423 men). Most adults with cystic fibrosis were found to be living fulfilling lives into adulthood. Significantly fewer men were married or cohabiting than women (110 (26%) men, 175 (44%) women). 420 (55%) responders were working, and of these 235 (56%) had less than two weeks'' sick leave a year. Half of those not employed gave ill health as the reason. Revealing that they had cystic fibrosis at job interviews reduced likelihood of being employed for those with mild to moderate disease. People with cystic fibrosis had been less successful than the general population in achieving O level or equivalent qualifications, but more successful in achieving A level or higher qualifications. Achievement of any qualifications enhanced employment prospects irrespective of disease severity. CONCLUSION--Contrary to an image of chronic ill health and disability, a high proportion of adults with cystic fibrosis are living full and productive lives. 相似文献
17.
Characterization of the cell kinetics and growth properties of cystic fibrosis diploid fibroblasts in vitro. 总被引:1,自引:0,他引:1
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The population growth kinetics of human diploid skin fibroblasts derived from cystic fibrosis homozygotes and heterozygotes and from normal subjects were investigated. Our data suggest the following: 1. Population doubling times increase with time in culture, with no significant differences observed among the three genotypes tested, when data were compared at the same subculture times or phases of growth. 2. The fraction of dividing cells in a population decreased with the duration in which the cells were in culture. No significant differences were obtained for cells derived from the three genotypes. 3. Cell cycle times were very similar (18-20 hr) when comparing the normal and cystic fibrosis lines or when comparing cystic fibrosis lines in phases 1 and 2 of growth. 4. No significant variations in population doubling times or growth fractions could be attributed to age or sex of the biopsy donor. 5. Variability in growth fractions and doubling times was minimal through the eighth subculture period but was very great in older cultures (tenth subculture). 6. Changes in growth fractions and doubling times appear to be due to the possibility of "aging" of human diploid fibroblasts in culture rather than to the presence or absence of genes for cystic fibrosis. 7. It is strongly indicated that differences in cell kinetic parameters cannot be used as the basis for differentiation between cells derived from normal or cystic fibrosis genotypes. 相似文献
18.
We have previously shown that about 85% of the mutationsin 194 Belgian cystic fibrosis alleles could be detected by a reverse dot-blot assay (7). In the present study, 50 Belgian chromosomes were analyzed for mutations in the cystic fibrosis transmembrane conductance regulator gene by means of direct solid phase automatic sequencing of PCR products of individual exons. Twenty-six disease mutations and 14 polymorphisms were found. Twelve of these mutations and 3 polymorphisms were not described before. With the exception of one mutant allele carrying two mutations, these mutations were the only mutations found in the complete coding region and their exon/intron boundaries. The total sensitivity of mutant CF alleles that could be identified was 98.5%. Given the heterogeneity of these mutations, most of them very rare, CFTR mutation screening still remains rather complex in our population, and population screening, whether desirable or not, does not appear to be technically feasible with the methods currently available. 相似文献
19.
Karnajit Kumar Bepari Arup Kumar Malakar Prosenjit Paul Binata Halder Supriyo Chakraborty 《Bioinformation》2015,11(7):348-352
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance
regulator gene. This gene encodes a protein involved in epithelial anion channel. Cystic fibrosis is the most common life-limiting
genetic disorder in Caucasians; it also affects other ethnic groups like the Blacks and the Native Americans. Cystic fibrosis is
considered to be rare among individuals from the Indian subcontinent. We analyzed a total of 29 world׳s populations for cystic
fibrosis on the basis of gene frequency and heterozygosity. Among 29 countries Switzerland revealed the highest gene frequency
and heterozygosity for CF (0.022, 0.043) whereas Japan recorded the lowest values (0.002, 0.004) followed by India (0.004, 0.008).
Our analysis suggests that the prevalence of cystic fibrosis is very low in India. 相似文献
20.
《Molecular medicine today》1996,2(1):24-31
Genetic diseases presenting with different phenotypes are generally classified as distinct disorders before their molecular defect is revealed, as exemplified by the recent advance in understanding of the molecular biology of cystic fibrosis and an obstructive form of infertility, known as congenital absence of the vas deferens. The majority of men with congenital absence of the vas deferens have a defect in both copies of the CFTR gene and therefore represent a distinct phenotypic form of cystic fibrosis. These developments help us to gain new insight into the genetic basis of phenotypic variability and the possible contributing mechanisms in cystic fibrosis. Some of the lessons learned from the relationship between cystic fibrosis and congenital absence of the vas deferens may be useful in the understanding of other genetic disorders. 相似文献