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X Estivill

Publications and source records attributed to X Estivill.

At least 307 records · Page 17Linked to original sources
PubMed1990

Genetic differences in cystic fibrosis patients with and without pancreatic insufficiency. An Italian collaborative study.

To determine the number and frequency of mutations that occur at the cystic fibrosis locus (CF), we have examined the allele and haplotype frequencies of eight polymorphic DNA markers linked to CF in 163 Italian patients who were sub-divided according to their clinical presentations. The distribution of haplotypes for the tightly linked polymorphisms KM.19 and XV-2c differ significantly between patients with and those without pancreatic insufficiency. The haplotype found most commonly in CF chromosomes occurs much more frequently in pancreatic insufficient than in pancreatic sufficient patients. Among the 19 pancreatic sufficient patients, 6 (31.6%) show at least one copy of the rare KM.19 = 1, XV-2c = 2 haplotype, as against 16 of 138 patients (11.6%) with pancreatic insufficiency. In addition, only 5 pancreatic sufficient patients (26.3%) are homozygous for the common 2.1 haplotype, as compared with 88 patients (63.8%) with pancreatic insufficiency. These findings support the hypothesis of allelic heterogeneity at a single locus in CF and suggest that different mutations underlie the presence or absence of pancreatic insufficiency in this disorders.

Alleles↗
PubMed1990

Distribution of the delta F508 mutation in 194 Spanish cystic fibrosis families.

Spanish cystic fibrosis (CF) families (n = 194) have been analysed for the delta F508 mutation, and for closely linked DNA markers. The delta F508 mutation accounts for 50% of CF chromosomes. Four haplotypes are associated with the deletion, and at least seven haplotypes carry other mutations. The second major CF mutation is associated with pancreatic insufficiency and occurred in the same haplotype in which the delta F508 arose. Only 31% of Spanish CF patients with no family history of the disease can be accurately diagnosed; about 50% of CF carriers can be detected in the Spanish population.

Chromosome Deletion↗
PubMed1990

Cystic fibrosis mutation delta F508 in Finland: other mutations predominate.

The frequency of mutation delta F508 was determined in all 20 Finnish cystic fibrosis (CF) families with living affected children (19 with pancreatic insufficiency). delta F508 was detected in 18 out of 40 CF chromosomes (45%). At least two different mutations associated with pancreatic insufficiently have occurred in a rare haplotype defined by XV2c, CS.7, KM19 alleles 1 2 2. Geographical clustering of delta F508 and other mutations suggested that a founder effect and genetic drift have influenced the frequency of mutations causing CF in Finland.

Child↗
PubMed1990

A new polymorphic locus, D7S411, isolated by cloning from preparative pulse-field gels is close to the mutation causing cystic fibrosis.

The mutation causing cystic fibrosis (CF) has been localized to the DNA sequence of 700 kb bounded by the loci identified by the markers pMP6d-9 (D7S399) and pJ3.11 (D7S8). A 560-kb fragment obtained after SacII digestion of DNA from a cell line containing this region of human chromosome 7 in a mouse background was separated using pulse-field gel electrophoresis and isolated from the gel. The DNA was digested with BamHI prior to cloning into lambda EMBL3. Approximately 0.1% of the resulting clones contained human repetitive sequences, and 24 such recombinants were studied. Of these, 23 are on chromosome 7; 8 clones were duplicated, and of the 15 different recombinants, 7 are between MET and INT1L1, and a further 7 are between INT1L1 and pMP6d-9, leaving a single marker, pG2, which is between pMP6d-9 and pJ3.11. pG2 recognizes an RFLP with XbaI. A cosmid walk from pG2 has generated a further marker, H80, which recognizes an RFLP with PstI. This new locus (D7S411) divides the remaining region between the CF flanking markers, thereby making it more accessible to fine pulse-field mapping and allowing the precise localization of further clones to this region. Although it is not possible to position the CF locus unequivocally with respect to D7S411, both polymorphic markers at this locus exhibit low but significant linkage disequilibrium with CF, placing the emphasis for the search for the gene on the D7S399 to D7S411 interval of 250 kb.

Blotting, Southern↗
PubMed1990

The genotype of a new linked DNA marker, MP6d-9, is related to the clinical course of cystic fibrosis.

The clinical symptoms of a cohort of cystic fibrosis patients were related to their genotypes using RFLPs shown with MspI and the closely linked DNA marker MP6d-9. In the majority of CF chromosomes, the restriction site for MspI was present, and the genotype 2/2 was found most often in patients who were severely affected by the disease. The genotype 1/2 was significantly over-represented in patients with very mild clinical manifestations, including pancreatic sufficiency, absence of meconium ileus, and absence of Pseudomonas colonisation. When pancreatic dysfunction was present, the 1/2 genotype was associated with a mild form, while the 2/2 genotype was found in patients with severe insufficiency. None of our patients had the 1/1 genotype. These results indicate that the newly isolated MP6d-9 marker correlates with some important symptoms of cystic fibrosis.

Cystic Fibrosis↗
PubMed1990

Regional distribution of cystic fibrosis linked DNA haplotypes in Italy, a collaborative study.

In view of the reported variations of cystic fibrosis (CF) associated haplotypes among populations, a detailed analysis of the distribution of two tightly linked DNA markers (Xv-2c and KM.19) in 18 Italian regions was performed. Haplotypes were determined for 405 CF chromosomes carrying the mutation, and showed significant heterogeneity between the North, Center, and South of Italy and the island of Sardinia. KM.19/PstI Restriction Fragment Length Polymorphism (RFLP) showed significant heterogeneity in these four areas, and was statistically correlated with the geographic distribution of the disease, while Xv-2c/TaqI polymorphism, like the haplotypes of normal chromosomes, was more uniformly distributed over the same four areas. Correlation coefficients between the markers and the mutation have been used to obtain additional indications on the physical distance between the markers and the fibrosis locus.

Cystic Fibrosis↗
PubMed1989

[Detection of carriers and prenatal diagnosis of cystic fibrosis in Spanish families using DNA markers].

A molecular study of 36 Spanish families with cystic fibrosis (CF) patients is reported. The analysis of seven DNA polymorphisms adjacent to the CF gene permitted the diagnosis of 95% of the probable carriers and the antenatal diagnosis in the seven cases in which it was requested. The application of recombinant DNA techniques to the study of CF by means of the analysis of DNA markers linked to the CF gene is useful, not only to identify the latter, but also as a reference to investigate its molecular pathology and for diagnostic purposes in high risk families (families with involved members).

Cystic Fibrosis↗
PubMed1989

Cystic fibrosis in Finland: a molecular and genealogical study.

The incidence of cystic fibrosis (CF) in Finland is one tenth that in other Caucasian populations. To study the genetics of CF in Finland, we used a combined molecular and genealogical approach. Out of the 20 Finnish families with a living CF patient, 19 were typed for eight closely linked restriction fragment length polymorphisms (RFLP) at the MET, D7S8, and D7S23 loci. The birthplaces of the parents and grandparents were traced using population registries. Allele and haplotype frequencies in Finland are similar to those of other European and North American populations, but are modified by sampling: two regional CF gene clusters, evidently the results of a founder effect, were identified. Generally, the gene was evenly distributed over the population, carrier frequency being estimated at approximately 1.3%. We conclude that CF in Finland is caused by the common Caucasian mutation(s), and that the low frequency of the gene can be explained by a negative sampling effect and genetic drift.

Adult↗
PubMed1989

Linkage disequilibrium for DNA haplotypes near the cystic fibrosis locus in two south European populations.

Three polymorphic DNA marker loci (INT1L1, D7S23 and D7S399) map to a chromosomal region that is very close to the cystic fibrosis (CF) locus in terms of genetic distance. These marker loci have been used to analyse the linkage disequilibrium in 137 CF families from two South European countries (Italy and Spain). The markers can be analysed for differences in linkage disequilibrium more easily in these populations than in North Europeans, in whom the disequilibrium between the allelic systems defined by the probes and CF is much greater and on a "plateau" through the genetic region. The different levels of disequilibrium found in the studied populations suggest that D7S399 and D7S23 are both closer to CF than INT1L1, and provide additional information on the origins and homogeneity of the CF defect.

Cystic Fibrosis↗
PubMed1989

Isolation of a new DNA marker in linkage disequilibrium with cystic fibrosis, situated between J3.11 (D7S8) and IRP.

A cosmid library of recombinants containing nonmethylated CpG sites for rare-cutter restriction enzymes was used previously to isolate the gene IRP and four polymorphic DNA markers (pPT-3, pXV-2c, pCS.7, and pKM.19) which are close to and in linkage disequilibrium with the cystic fibrosis (CF) mutation. We have analyzed several new clones from the same library and have isolated a further cosmid, cNX.6d, which maps approximately 160 kb from CS.7, in the J3.11 direction. A DNA fragment (pMP6d-9) (D7S399) derived from cosmid cNX.6d detects a frequent polymorphism with MspI. Strong linkage disequilibrium between CF and MP6d-9 is found in European populations. Recombinations in two families suggest that CF is between the MspI polymorphic site recognized by pMP6d-9 and the polymorphism recognized by pJ3.11. The new marker is the closest, to date, to CF and will be useful for prenatal diagnosis and carrier testing.

Chromosome Mapping↗
PubMed1988

Genetic differences between cystic fibrosis with and without meconium ileus.

41 families with cystic fibrosis, (CF) were tested for restriction fragment length polymorphisms (RFLPs) detected by four DNA probes all of which are tightly linked to the CF gene. 17 of the families had an affected child with, and 24 had one without, meconium ileus. In all cases, CF segregates with these gene probes; however, those with and those without meconium ileus differed in haplotype for CF chromosomes with respect to pJ3.11, which suggests that because of multiallelism (different mutations of the same locus) some CF patients present with meconium ileus and others do not.

Alleles↗