Search PubMed⌕ Search

Biomedical subjects

A Taillandier

Publications and source records attributed to A Taillandier.

11 recordsLinked to original sources
PubMed1996

Recurrent and unexpected segregation of the FMR1 CGG repeat in a family with fragile X syndrome.

Fragile X syndrome, the most common cause of hereditary mental retardation, results from amplification of a CGG trinucleotide repeat in the FMR1 gene. The transmission of the CGG repeat from premutated individuals to their premutated descendants is usually unstable, showing an increase in the size of the repeat. We report here a family which exhibits recurrent and unexpected transmission of the maternal premutation to three daughters. The first daughter exhibited mosaicism with two premutated alleles, one contracted and the other expanded. The second daughter showed a reversion from the maternal premutation to the normal range, and the third carried an expanded premutated allele associated with an expanded paternal allele within the normal range. These variations in the size of the CGG repeat may result from many different mechanisms such as DNA polymerase slippage on the leading or lagging strand during replication, large contractions of repeats on the parental strand during replication, or recombination through unequal crossover between sister chromatids. Our results suggest that the variation of the CGG premutated alleles in this family may be the result of intrinsic instability associated with a trans-acting factor such as a mismatch repair gene product.

Female↗
PubMed1996

Analysis of germline variation at the FMR1 CGG repeat shows variation in the normal-premutated borderline range.

In order to characterize the dynamics of CGG repeat instability at the fragile X syndrome locus (FMR1 gene), we have used small pool PCR to estimate the mutation rate within germline (sperm) and somatic tissue (leukocytes) of two normal males, one carrying the most common 29 CGG repeats allele, the other carrying a borderline normal-premutated allele of 55 repeats. Large contractions and moderate expansions of the repeat were found in sperm and blood for the 55 repeat allele while almost no variation was found in sperm or blood with the 29 repeat allele. Somatic blood DNA exhibited fewer expansions and contractions than sperm. Contractions were more frequent than expansions, and all the expansions were found in the +4 to +10 repeats range, while most of the contractions were found in the -10 to -30 range, suggesting that a subset of contractions results from a distinct mechanism. These results also suggest that the dynamics of the CGG repeat could be partly due to germline instability within the high normal or premutated ranges.

Fragile X Messenger Ribonucleoprotein 1↗
PubMed1994

Transition from normal to premutated alleles in fragile X syndrome results from a multistep process.

In fragile X syndrome, the most common cause of inherited mental retardation, phenotypic expression has been linked to a region containing a repetitive sequence, (CGG)n, that appears to lengthen dramatically in fragile X patients and to show length variation in normal individuals. In order to investigate possible mechanisms responsible for further expansion of CGG in the normal population, we selected 31 normal unrelated X chromosomes carrying either the high-risk DX204-AC155 or DX196-AC151 haplotypes, as defined by the flanking microsatellites, DXS548 and FRAXAC2. Nearly 100% of CGGs with more than 35 repeats were found on DX204-AC155 haplotypes, with a mean length significantly higher and much more variable than in normal individuals carrying other haplotypes including the high-risk haplotype DX196-AC151. These findings suggest that the transition from the normal to the abnormal range occurs by a multistep process, a primary event, such as unequal crossing-over, leading to increased size and moderate instability of the repeat, and from which DNA polymerase slippage could lead to recurrent premutations. Our results also suggest that the upper limit of the normal range is roughly 35 repeats in the fragile X gene. The 36-54 repeats range would define an intermediate allele only observed, up to now, in DX204-AC155 fragile X chromosomes.

Analysis of Variance↗
PubMed1991

Nearly 80% of cystic fibrosis heterozygotes and 64% of couples at risk may be detected through a unique screening of four mutations by ASO reverse dot blot.

A technique allowing the simultaneous screening of the four main CF mutations in the French population (delta F508, delta I507, G542X, S549N) has been developed by means of allele sequence-specific oligonucleotide (ASO) reverse dot blot. Using a strategy proposed by R. K. Saïki et al. (1989, Proc. Natl. Acad. Sci. USA 86: 6230-6234) for HLA-DQA, the seven ASOs for normal and mutant CF alleles were given a homopolymer T tail with terminal deoxyribonucleotidyltransferase and then immobilized on a nylon membrane. T-tail homopolymers were preferentially bound to the nylon, leaving the specific ASO sequences free to hybridize with amplified and radiolabeled exons 10 and 11 of a patient. These exons were simultaneously coamplified by a multiplex PCR and radiolabeled by random priming. ASO reverse dot blot currently appears to be the most efficient, rapid, and economic means of screening the population for CF mutations. This screening can detect nearly 80% of carriers and 64% of couples at risk and could prevent the birth of CF-affected infants in these families.

Alleles↗
PubMed1991

Nine mutations in the cystic fibrosis (CF) gene account for 80% of the CF chromosomes in French patients.

Thirteen mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been screened in a French sample of 185 cystic fibrosis (CF) patients, together with their respective associated RFLP haplotypes at the linked D7S23 locus (XV2C and KM19 markers). The respective frequencies of the mutations showed that 9 of them account for 80% of the CF chromosomes. Implications for prenatal diagnosis and heterozygote detection are defined and discussed. The well-known great excess of RFLP B marker within CF chromosomes is partially explained by two already characterized mutations highly associated with haplotype B: delta F508 and G542X. Similarly, the excess of haplotype D within CF chromosomes is partially explained by the association between delta I507 and this haplotype. These results may suggest the existence of two still untested or uncharacterized mutations, whose frequencies could be near 1%, one which would be associated with haplotype B and a second which would be associated with haplotype D. The possible cause of the specific association between most of the main different CF mutations and the RFLP haplotype B is discussed.

Alleles↗
PubMed1990

Studies of RFLP closely linked to the cystic fibrosis locus throughout Europe lead to new considerations in populations genetics.

The prenatal diagnosis of cystic fibrosis is now routinely performed by using two probes tightly linked to the CF locus (XV2C and KM19). These probes have been shown to exhibit a strong linkage disequilibrium with the CF locus. Our data (103 families) have been pooled with other French data (237 families). They are consistent with the hypothesis of a unique ancestral mutation initially associated with a B (D1E2) restriction fragment length polymorphism (RFLP) haplotype, subsequently reassociated by cross-over with A, C or D haplotypes. Assuming such an hypothesis, the mutation is supposed to be 3000-6000 years old, depending on generation length and the true recombination ratio between the KM19 and CF loci. Up-to-date Spanish, Danish and Greek data are reported together with other previously published population data in order to discuss the geographic origin and age of the mutation in Europe. The action of selection in terms of heterozygote advantage and distorsion of segregation is discussed.

Cystic Fibrosis↗
PubMed1990

Genotyping of the Spanish cystic fibrosis population at the delta F508 mutation site and RFLP linked loci.

Spanish families (n = 75) with at least one affected cystic fibrosis (CF) child were typed for restriction fragment length polymorphisms (RFLPs) by the probes XV2c, KM19, and pMP6d-9. These families were also studied at the 508 mutation site by the polymerase chain reaction method. We have studied the linkage disequilibrium between these markers and the CF mutations, the probable number of independent secondary CFX (non-delta F508) mutations, and the genetic differences between Spain and Western Europe.

Chromosome Deletion↗
PubMed1990

The cystic fibrosis delta F508 mutation in the French population.

French families (n = 129) with at least one cystic fibrosis (CF) affected child and 44 unrelated subjects from the general population were tested for the presence of the delta F508 mutation by the polymerase chain reaction. The delta F508/CF mutation ratio (CF: uncharacterised CF mutations) was tested in the CF families with and without meconium ileus. The association between delta F508 and CF mutations and restriction fragment length polymorphism haplotypes (XV2c and KM19) has been estimated; these data suggest that the CF chromosomes include a panel of independent and probably different mutations.

Cystic Fibrosis↗
PubMed1989

Genetic heterogeneity between two clinical forms of cystic fibrosis evidenced by familial analysis and linked DNA probes.

CF heterogeneity has been evidenced from both clinical and genetic observations. At least two clinical forms of CF are easily distinguishable: CF with meconium ileus and CF without meconium ileus. The results of prenatal diagnosis have shown that the recurrence rates of CF are different in these two clinical forms. Molecular analysis of Restriction Fragment Length Polymorphisms (RFLPs) tightly linked to the cystic fibrosis (CF) gene defined several types of CF and normal chromosomes in a French sample of 64 families with CF. The CF mutation is tightly linked to one XV-2C and KM19 RFLPs haplotype but is differently linked to J3.11 RFLP alleles, depending on whether or not the clinical form of CF is associated with ileus. A distortion of the segregation ratio observed between normal and CF haplotypes in the families with ileus could explain the high recurrence rate of CF in such families.

Alleles↗