CFTR haplotype backgrounds on normal and mutant CFTR genes

Cuppens, Harry; Teng, Hui; Raeymaekers, Peter; Boeck, Christiane De; Jj, Cassiman

doi:10.1093/hmg/3.4.607

Cited by 69 publications

(62 citation statements)

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“…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

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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...

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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

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“…This also verifies that the duplication occurred in trans to the ⌬F508 mutation in the proband. Because the ⌬F508 mutation seems to be associated exclusively with the IVS8-10TG/IVS8-9T/A1540 haplotype, 17,18 by extrapolation, the novel duplication is assumed to have occurred on the IVS8-11TG/IVS8-7T/G1540 haplotype.…”

Section: Detection Of Duplication 6b-10 By Sqf Pcrmentioning

confidence: 99%

Characterization of a Recurrent Novel Large Duplication in the Cystic Fibrosis Transmembrane Conductance Regulator Gene

Hantash

Redman

Goos

et al. 2007

The Journal of Molecular Diagnostics

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Recently, DNA rearrangements in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been described with increasing frequency. These large DNA rearrangements are not detected using conventional methods of DNA sequencing, singlestrand conformational polymorphism, or denaturing high-performance liquid chromatography. We and others have described methods to detect such rearrangements in the CFTR gene. With one exception, all rearrangements reported thus far are single or multiple exon deletions, whereas only one report has described a large duplication. We describe here the detection and characterization of a novel large duplication in the CFTR gene. This duplication, referred to as gIVS6a ؉ 415_IVS10 ؉ 2987Dup26817bp, was detected in a classic CF female patient whose other mutation was ⌬F508. The duplication was inherited paternally. The duplication encompassed exons 6b to 10 and occurred on the IVS8-11TG/IVS8-7T/ G1540 haplotype. This large duplication is predicted to result in the production of a truncated CFTR protein lacking the terminal part of NBD1 domain and beyond and thus can be considered a null allele. The combination of the ⌬F508 and gIVS6a ؉ 415_IVS10 ؉ 2987Dup26817bp mutation probably causes the severe CF phenotype in this patient. We designed a simple polymerase chain reaction test to detect the duplication, and we further detected the same duplication from another independent laboratory. The duplication breakpoint is identical in all three patients, suggesting a likely founder mutation. (J Mol Diagn

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“…The three allele (5T, 7T, 9T) polymorphic tract of thymidines in intron 8 (IVS8-polyT), of which the 5T allele acts as a mild mutation, caused reduced levels of normal CFTR mRNA due to deletion of exon 9, was also analyzed using denaturing gradient gel electrophoresis (DGGE) [3,4]. The M470V polymorphism was also analyzed in all samples [6,27].…”

Section: Analyses Of Cftr Gene Mutationsmentioning

confidence: 99%

Clinical, Andrological and Genetic Characteristics of Patients With Congenital Bilateral Absence of Vas Deferens (Cbavd)

Şamlı

Samli

Yılmaz

et al. 2006

Archives of Andrology

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CFTR haplotype backgrounds on normal and mutant CFTR genes

Cited by 69 publications

References 0 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

Characterization of a Recurrent Novel Large Duplication in the Cystic Fibrosis Transmembrane Conductance Regulator Gene

Clinical, Andrological and Genetic Characteristics of Patients With Congenital Bilateral Absence of Vas Deferens (Cbavd)

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