Biomedical subjects
Publications and source records attributed to G Lucotte.
We have collected 76 parent-offspring (CAG)n values in 60 French Huntington's disease (HD) pedigrees. The analysis of intergenerational alterations in CAG repeat length shows that there is a correlation between repeat instability and parental repeat length. Paternally inherited cases are characterized by a preferential trend towards an increase in range of repeat sizes in offspring of HD patients.
We collected 7 Friedreich ataxia (FRDA) pedigrees from France. All cases but one family were homozygous for an unstable GAA trinucleotide expansion in the first intron of the frataxin gene. In this peculiar pedigree absence of the GAA expansion supports the notion of possible genetic heterogeneity of FRDA.
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The frequencies of five mutations of the debrisoquine 4-hydroxylase (CYP2D6) gene (mutations D6-A, B, C, D, and T), corresponding to poor metabolizer (PM) phenotypes, were determined by restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) in 47 patients with Parkinson disease, and compared with the findings in 47 healthy controls. These mutant alleles were about twice as frequent among patients as in controls, with an approximate relative risk ratio of 2.12 (95% confidence interval, 1.41-2.62). There seem to be no significant differences in frequencies of mutant genotypes in patients among gender and modalities of response with levodopa therapy; but frequency of the mutations was slightly enhanced after age-at-onset of 60 years. Mutations D6-B, D, and T were detected in 7 patients belonging to 10 Parkinson pedigrees.
We describe a semiquantitative method to measure hepatitis C virus (HCV) viral particle numbers, by carrying out reverse-transcription polymerase chain reaction (RT-PCR) on serial dilutions of serum samples. The virus concentrations measured were 10(3)-10(6) viral particles ml-1 of serum. The method described is relatively quick, and the only required manipulation is dilution of the serum. An optimal RT-PCR method is used for diluted and undiluted samples.
One Y-specific DNA polymorphism (p49/ TaqI) was studied in a sample of 97 French Basques and compared with those found in 7 other French, Iberian, and Italian populations. A particularly high frequency (72.2%) of Y-haplotype XV was observed in Basques, compared to values (mean of 41%) obtained in other Western Europeans. Basques were also characterized by virtual absence, or presence at a low level, of the South or Near Eastern haplotypes XII, VII, and VIII. Considered together, these results confirm that Basques are a very ancient European population which has had little previous contact with the Neolithics.
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DNA samples from Ashkenazic and Sephardic Jews were studied with the Y-chromosome-specific DNA probes p49f and p49a to screen for restriction fragment length polymorphisms and haplotypes. Two haplotypes (VII and VIII) are the most widespread, representing about 50% of the total number of haplotypes in Jews. The major haplotype in Oriental Jews is haplotype VIII (85.1%); haplotype VIII is also the major haplotype in the Djerban Jews (77.5%) (Djerban Jews represent probably one of the oldest Jewish communities). Together these results confirm that haplotype VIII is the ancestral haplotype in Jews.
The deletion of 3bp at codon positions 2642-2645 (delta 2642) of the gene mutated in Huntington's disease (HD) was analysed on the normal (N) and HD chromosomes of 79 French families affected with HD, and previously typed for the (CAG)n repeats. delta 2642 Polymorphism has been found over-represented on HD chromosomes, the relative risk of HD with the deletion being at a value of 8.26. In this study, the presence of the deleted allele on HD chromosomes increases the (CAG)n number (47.93 +/- 1.80 versus 43.50 +/- 2.78) and decreases the age of onset (41.34 +/- 2.09 versus 36.90 +/- 2.41) in the patients with versus without delta 2642; so the deletion may add to the severity of the disease. Our studies of delta 2642 on N chromosomes confirm that the deletion event occurs on N chromosomes with a (CAG)n allele length at the upper end of the normal size range.
Apoliprotein E, type epsilon 4 allele (ApoE-epsilon 4) is associated with late-onset sporadic Alzheimer's disease (AD). We have found that the cumulative probability of remaining unaffected over time decreases for each dose of ApoE-epsilon 4 in sporadic, late-onset French AD. The effect of genotypes on age at onset of AD was analyzed using the product limit method, to compare unaffected groups during aging.
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A simple and rapid polymerase chain reaction (PCR) procedure was developed for simultaneous detection and typing of herpes simplex virus (HSV) types 1 and 2. It was possible to detect and type HSV using two primers pairs in a simultaneous double PCR reaction, where the type of HSV present was determined on the basis of an ethidium-bromide-stained band after agarose gel electrophoresis. This PCR assay was tested on about 500 clinical specimens.
Examination of the European geographic patterns of the 10 relatively most frequent cystic fibrosis mutations, other than the DF508 one, shows that a founder effect is apparent for a number of them. The most evident examples are for the W1282X mutation in Jews, with a probable Asian origin, and the G551D and R117H mutations in Celts. Geographic distributions indicate that the main focus of the 621 + 1 G-->T and DI507 mutations is probably located in Wales. Also, the R1162X mutation probably originates from a circumscribed north Italian region. The N1303K mutation has a wide range in Europe with a clear preponderance in southern countries. Even the relatively common G542X and 1717.1 G-->A mutations have a local preponderance in Spain and Sicily and in northern Italy, respectively. Likelihood estimates for recurrent mutation and identity by descent strongly support the hypothesis of recurrence for the (mainly German) mutation R553X.
The frequencies of DF508, the main cystic fibrosis mutation, vary among different populations in Western Europe; they are higher in northwestern Europeans than in southeastern populations. Our new analysis is based on results from 66 different laboratories on 17,886 cystic fibrosis chromosomes (from 70 locations and 26 countries). The correlation between DF508 frequency values and cystic fibrosis incidence is calculated in the corresponding groups.
Molecular characterization of Charcot-Marie-Tooth patients in 15 pedigree from France: We collected 15 Charcot-Marie-Tooth (CMT) pedigrees from France. DNA polymorphisms analysis by Southern blotting with probes at the D17S122 locus demonstrated 17p duplication in three CMT1a families and in one sporadic case. Two families affected by CMT2 showed no evidence of the duplication.
Apolipoprotein E, type epsilon 4 allele (ApoE epsilon 4), is associated with late-onset sporadic Alzheimer's disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for epsilon 4 allele frequencies). These data support the involvement of ApoE epsilon 4 allele as a very important risk factor for the clinical expression of AD.
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