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F Clerget-Darpoux

Publications and source records attributed to F Clerget-Darpoux.

125 records · Page 7Linked to original sources
PubMed1986

Interactive effect of HLA and Gm tested in a study of 135 juvenile insulin-dependent diabetic families.

Interaction between HLA and Gm for susceptibility to insulin-dependent diabetes (IDD) has been studied in 135 IDD families comparing HLA and Gm phenotype distributions in patients and sibling controls. The association analysis comparing the 135 index cases to 124 sibling controls did not show any significant interaction, but only a tendency for Gm 4,5 phenotypes to be more frequent in IDD patients, particularly in those who carried DR3/X. The sib pair analysis of 16 pairs of affected sibs did not show any distortion of segregation of Gm. On the other hand, among 98 sib pairs of one affected and one nonaffected sib, there was a significant distortion in favour of sib pairs with non-identical Gm phenotypes. However, no interaction between HLA and Gm was found. These results provide suggestive evidence that Gm or a locus very close to Gm could be involved in susceptibility to IDD.

Adolescent↗
PubMed1986

Clinical methods in psychiatric genetics. III. Environmental stratification may simulate a genetic effect in adoption studies.

In adoption studies, the possibility of inadvertent matching between biological and adoptive parents for some environmental variable (known or unknown) correlated with illness must be considered. We examine such bias quantitatively and show how a genetic effect can be simulated. Existence of a genetic effect which is independent of environmental correlation can be accepted, when the frequency of a disease in adoptees who have a biological parent affected and no adoptive parents affected is significantly greater than the frequency of the disease in adoptees who have an adopted parent affected and no biological parents affected. The published data on schizophrenia, alcoholism, and criminality do not exclude the possibility of undetected environmental correlations simulating a genetic effect, according to this direct criterion.

Adoption↗
PubMed1986

Effects of misspecifying genetic parameters in lod score analysis.

The lod score method is widely used to test linkage and to estimate the recombination fraction between a disease locus and a marker locus. The parameters (gene frequency, penetrance, and degree of dominance) are assumed to be known at each locus. This condition may not be fulfilled at the disease locus. In this paper, we evaluate the errors due to the use of wrong parameters. The power of the linkage test is sensitive to the degree of dominance, and slightly to the penetrance, but not to the gene frequency. In contrast, the estimation of the recombination fraction may be strongly affected by an error on any genetic parameter.

Alleles↗
PubMed1985

Association between a genetic trait and a marker: discrimination between epistasis and gametic disequilibrium.

We reconsider the method of Ott and Falk (1982) for the analysis of genetic linkage and of epistasis in the presence of phenotypic association. Their approach is extended to allow for gametic disequilibrium between marker and trait loci. We show that epistasis and tight linkage with gametic disequilibrium may be indistinguishable as explanations of association even in a very large pedigree.

Alleles↗
PubMed1985

[Interaction between HLA and Gm for susceptibility to insulin-dependent diabetes].

It is now well established that HLA system is involved in the susceptibility to Type 1 diabetes mellitus. In this study we look for a possible effect of the Gm system. A first study (cases-controls) suggests that among individuals who had HLA-DR3 but not HLA-DR4 or HLA-DR4 without HLA-DR3, there is a possible effect of the phenotype Gm3,23,5 or Gm3,-5 in the susceptibility to IDDM. Moreover, we have tested by the sibpair method whether HLA and Gm are transmitted independently from IDDM: an unaffected sib, sharing the same HLA haplotypes than an affected individual, seems to be more often phenotypically different at the Gm loci.

Diabetes Mellitus, Type 1↗
PubMed1984

HLA and susceptibility to multiple sclerosis.

The study of the joint segregation of multiple sclerosis and HLA, using affected sib pairs as well as whole pedigrees, shows that these two traits are not independently transmitted. The hypothesis of a single susceptibility locus inside HLA region could explain all the observed data, only if a high gene frequency, a very low penetrance, and some environmental correlation between relatives are assumed. Linkage analysis performed on the basis of this hypothesis for 58 multiple sclerosis families concludes to a strict linkage. We obtained a maximum score of 3.11 at theta = 0.00 for a dominant gene of frequency 0.18 and penetrance of 0.02. This result contrasts with the large recombination fraction obtained by other authors and the discrepancy is explained by the very low gene frequency used in their analysis. Some environmental correlation, in addition to the genetic determinant in HLA region, may explain the overall familial aggregation, but an alternative is the existence of additional genetic determinants.

Gene Frequency↗
PubMed1984

HLA-associated diseases: a new method for performing linkage analysis with other markers than HLA.

It has been shown that genetic factors within the HLA region are involved in the etiology of several diseases. For some of these, the existence of another genetic factor has been suggested, although not proven. A possible way to give evidence for another locus (G) is to show that the disease and an unlinked HLA-marker locus (M) do not segregate independently. The usual lod-score method, which assumes monogenic inheritance, is inappropriate for this test. We propose a correction of this method for performing a linkage analysis between the G and M loci, taking into account the role of HLA. A very simple way of using the HLA information is by modifying, for each individual of a pedigree, the penetrance values at the G locus according to the number of HLA haplotypes shared with the index case. These penetrance values are inferred from the observed IBD (identity-by-descent) distribution of HLA haplotypes in a sample of affected sib-pairs. The advantage of using this empirical distribution is that it is not based on any assumptions concerning the mode of inheritance at the HLA-linked locus. This correction method was established using a two-locus model with restrictive assumptions. Its value is discussed for various sets of parameters in more general and realistic two-locus models using simulations.

Chromosome Mapping↗
PubMed1982

Relationship of HLA to major affective disorder not supported.

A recently published report (Weitkamp et al., 1981) concludes that a major susceptibility locus for depression is located in the HLA region of chromosome 6. This conclusion was based on increased sharing of HLA haplotypes in affected sib pairs and nonrandom segregation of HLA types and illness in families. However, both of these findings were true only for specific subsamples of the data. Here, we suggest that the criteria used to subdivide the data are not theoretically justified. In addition, we show that we cannot replicate their findings in our own new data. Our data do not support any relationship of HLA type to affective disorders.

Affective Disorders, Psychotic↗
PubMed1980

Application of the lod score method to detection of linkage between HLA and juvenile insulin-dependent diabetes.

The lod score method has been applied to 28 informative families with at least one child suffering from juvenile insulin-dependent diabetes (JIDD), assuming autosomal recessive inheritance, for detection of linkage between HLA and a susceptibility locus for this disease. These 28 families were pooled with 21 other families from the literature. The maximum lod scores were obtained for recombination fractions from 4 to 16%, according to the level of penetrance (10 to 90%). These high estimates of the recombination fraction are not in agreement with the hypothesis that the association between JIDD and specific HLA haplotypes is due to a simple linkage disequilibrium between the HLA region and a susceptibility locus for JIDD.

Chromosome Mapping↗
PubMedDate not supplied

Interactive effect of HLA and Gm and genetic heterogeneity tested in 79 rheumatoid arthritis families.

The hypothesis that there is an interactive effect between HLA and Gm genes in rheumatoid arthritis (RA) was tested in a sample of 79 RA families. An analysis, of the joint segregation of these two markers in RA sibpairs, confirmed the previously described effect of HLA in RA but did not provide evidence of an independent effect of Gm alone or in interaction with HLA. The additional hypothesis that the previously described correlation between RA and autoimmune thyroid disease is due to genetic factors, was also investigated in relation to HLA and Gm. Therefore, we examined the segregation of HLA and Gm in RA sibships depending on the presence or the absence of autoimmune thyroid disorder. This analysis showed significant heterogeneity in HLA segregation (P = 0.02) with an HLA effect restricted only to sibships without thyroid disease. There was no evidence that thyroid disease influenced Gm segregation (P = 0.19). The effect of thyroid disease on HLA segregation suggests that the familial association between RA and autoimmune thyroid disease is at least partially due to genetic factors.

Arthritis, Rheumatoid↗