CFTR haplotypic variability for normal and mutant genes in cystic fibrosis families from southern France

Claustres, Mireille; Desgeorges, Marie; Moine, Philippe; Morral, Núria; Estivill, Xavier

doi:10.1007/s004390050219

Cited by 32 publications

(32 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, interestingly, the M allele has been reported for some CF mutations, and particularly for ∆F508 [28][29][30] , most mutations have been found to be associated with the M470 allele, while the V470 allele shows an extended haplotype homozygosity [27,31,32] . The T7 allele tracts were combined with (TG)11 and (TG)12 repeats, but the T7-(TG)10 haplotype was not found in our study.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population

Qin¹,

Ding²,

Wei³

2008

WJG

View full text Add to dashboard Cite

Huang Q, Ding W, Wei MX. Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population. World J Gastroenterol 2008; 14(12): 1925-1930 INTRODUCTIONThe cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7q31 spans approximately 250 kb of DNA and encodes 27 exons encodes [1] . The CFTR gene encodes a cAMP-and ATP-dependent chloride channel that is present in the apical membrane of the epithelial cells that line most exocrine glands [2] . Phosphorylation of the regulatory domain by protein kinase A, followed by binding and hydrolysis of ATP at both nucleotide-binding domains, regulates the transport of chloride ions through the channel [3] . Absence, reduced levels, or malfunction of the CFTR protein results in cystic fibrosis (CF), and CF-like diseases such as congenital bilateral absence of the vas deferens (CBAVD) [4,5] , bronchiectasis [6] and chronic pancreatitis [7] . Since the discovery of the CFTR gene, more than 1000 mutations and 200 polymorphisms have been identified [8] . CF is one of the most common autosomal recessive disorders in Caucasians, with an incidence of approximately 1 in 2500 Caucasian births and a carrier frequency of approximately 1 in 25. However, in Asians, the prevalence of CF is very low, with an incidence of approximately 1 in 100 000, and in particular, the severe mutations, such as ∆F508, G542X and N1303K, are rarely found in Asians. Previous studies have demonstrated that polymorphisms outside the CFTR gene [9,10] , as well as within the gene, may affect transcription or function of the CFTR protein and modify the phenotype of some CF mutations. It has been mentioned that poly-T, TG-repeats and M470V polymorphisms play a role in the development of CF-like diseases. The poly-T tract located at the junction of intron Abstract AIM: To investigate the three important cystic fibrosis transmembrane conductance regulator (CFTR ) haplotypes poly-T, TG-repeats and the M470V polymorphisms in the Chinese population, and to compare their distribution with that in Caucasians and other Asian populations. RAPID COMMUNICATION METHODS:Genomic DNA was extracted from blood leukocytes. Exons 9 and 10 of the CFTR gene were obtained through polymerase chain reaction (PCR). Exon 9 DNA sequences were directly detected by an automated sequencer and poly-T and TG-repeats were identified by direct sequence analysis. Pure exon 10 PCRamplified products were digested by Hph Ⅰ restriction enzyme and the M470V mutation was detected by the AGE photos of digestion products.RESULTS: T7 was the most common (93.6%) haplotype and the (TG)11 frequency of 57.2% and (TG)12 frequency of 40.9% were dominant haplotypes in the junction of intron 8 (IVS-8) and exon 9. The frequency of T5 was 3.8% and all T5 allele tracts (10 alleles) were joined with (TG)12. Four new alleles of T6 (1.5%) were found in three healthy individuals. In exon 10, the V allele (56.1%) was slightly more frequent than the M allele (43.9%), and the M/V (45.5%) was the dominan...

show abstract

Section: Discussionmentioning

confidence: 99%

Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population

Qin¹,

Ding²,

Wei³

2008

WJG

View full text Add to dashboard Cite

show abstract

“…Our data together with the study of Desgeorges et al [1995] showed that the p.L206W mutation was associated with one haplotype using this set of polymorphic sites. A more extensive study with seven diallelic and three multiallelic markers describes a second p.L206W-associated haplotype, as the result of recombination [Claustres et al, 1996]. The p.L206W mutation was found to account for 0.6% of the CF genes identified in our specialized center, and 0.9% in CBAVD patients.…”

Section: Genotype Data Among Cf Patients With L206w Mutationmentioning

confidence: 97%

Misprocessing of theCFTRprotein leads to mild cystic fibrosis phenotype

et al. 2005

View full text Add to dashboard Cite

Cystic fibrosis (CF) is mainly caused by mutations that interfere with the biosynthetic folding of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. The aim of this study was to determine the mechanism of dysfunction of a disease-causing mutation associated with variable phenotypes. In order to attain these objectives, we studied the effect of the p.L206W mutation on CFTR protein production and function, and we examined the genotype-phenotype correlation of [p.L206W]+[p.F508del] patients. We showed that p.L206W is a processing (class II) mutation since the CFTR biosynthetic pathway was severely impaired, whereas single-channel measurements indicated ion conductance similar to the wild-type protein. These data raise the larger question of the phenotypic variability of class II mutants, including p.F508del. Since multiple potential partners could modify the processing of the CFTR protein during its course to the cell surface, environmental and other genetic factors might contribute to this variability.

show abstract

“…This finding has been tentatively interpreted as an example of sweeping selection caused by the birth of an advantageous mutation in a V gene; from that moment onwards this hypothetical gene would have rapidly spread [3] while accumulating some variability through recombination and recent mutational events. This Fallele-restricted_ variability has been reported also for some CF mutations, and particularly for F508del (hereafter sometimes designated simply F mutation), in various European countries [4][5][6], thus allowing one to subdivide the general population into classes of individuals having a different risk of being carriers of a CF mutation. We decided to quantify this differential risk in one Southern European country, and to test this finding in a second Central European country, by determining the frequency of the M and the V alleles in a sample of NonF508del CF genes (hereafter designated as NonF CF mutations).…”

Section: Introductionmentioning

confidence: 92%

Highly preferential association of NonF508del CF mutations with the M470 allele

Ciminelli

Bonizzato

Bombieri

et al. 2007

Journal of Cystic Fibrosis

View full text Add to dashboard Cite

Besides the possible biological significance of this association, the possibility of exploiting it for a pilot screening program has been explored in a local North East Italian population for which CF patients were characterized for their CF mutation. General M470V genotyping followed by common CF mutation screening limited to couples in which each partner carries at least one M allele would need testing only 39% of the couples, which contribute 89% of the total risk, with a cost benefit.

show abstract

CFTR haplotypic variability for normal and mutant genes in cystic fibrosis families from southern France

Cited by 32 publications

References 23 publications

Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population

Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population

Misprocessing of theCFTRprotein leads to mild cystic fibrosis phenotype

Highly preferential association of NonF508del CF mutations with the M470 allele

Contact Info

Product

Resources

About