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Biomedical subjects

L Iselius

Publications and source records attributed to L Iselius.

At least 91 records · Page 5Linked to original sources
PubMed1983

Genetic susceptibility to multiple sclerosis: a review.

We review evidence on genetic susceptibility to multiple sclerosis provided by studies of family resemblance, migrants, twins, HLA-associations, and segregation and linkage analyses. The higher concordance rate in MZ than DZ twins and the increasing prevalence with increasing degree of kinship to propositi suggest that genetic factors are involved in the aetiology of MS. Nonetheless, the low overall twin concordance rates, the increased prevalence of MS in DZ twins over siblings, and the weight of evidence from migrant studies strongly suggest the involvement of environmental factors as well. These results can be reconciled by hypothesizing an MS susceptibility gene with reduced penetrance, where full phenotypic expression depends on critical environmental exposures. The location of this gene in or near the HLA region is suggested by the reports of HLA-MS associations and is supported by results of formal linkage analyses. Two general hypotheses have emerged. One involves loose linkage with no heterogeneity while the other involves very tight linkage and substantial heterogeneity, ie no linkage in 25% of the pedigrees. Since the MS gene is probably not a recent mutation, the hypothesis of loose linkage requires one to postulate intense selection to maintain linkage disequilibrium. It is primarily because of this intense selection that we currently favour the hypothesis of tight linkage with heterogeneity over any single-gene hypothesis involving loose linkage, given our present biological knowledge. Areas for future research are suggested.

Diseases in Twins↗
PubMed1983

Genetic regulation of the red cell uroporphyrinogen-I-synthetase level in families with acute intermittent porphyria.

The uroporphyrinogen-I-synthetase (UIS) activity in red blood cells was determined in 206 individuals from 48 nuclear families ascertained through a proband with acute intermittent porphyria (AIP) as well as in 230 members belonging to 53 nuclear families with no signs of AIP. Complex segregation analysis showed that the UIS activity is regulated by a major locus (a dominant or additive gene) together with a considerable multifactorial component.

Ammonia-Lyases↗
PubMed1983

Family resemblance for blood pressure.

Familial correlations are available for individuals reared by biological and foster parents, with and without indices of relevant environment. Five data sets give estimates of genetic heritability which range from 0.194 to 0.360 for systolic pressure and from 0.147 to 0.346 for diastolic pressure. Concomitant estimates of cultural heritability due to common family environment range from 0.042 to 0.183 for systolic pressure and from 0.008 to 0.310 for diastolic pressure. There is good resolution of genetic and environmental determinants. Most of the variance is due to random environment and errors of measurement. Although estimates of variance components are spatiotemporally limited to particular populations, there is good agreement among data sets.

Adult↗
PubMed1983

Heterozygous expression of insulin-dependent diabetes mellitus (IDDM) determinants in the HLA system.

HLA phenotypes of cases with insulin-dependent diabetes mellitus (IDDM) and identity by descent of HLA haplotypes in affected sib-pairs support an intermediate model in which morbid risk is increased by one HLA-linked IDDM determinant, and greatly increased by two determinants, which may be qualitatively different in DR3 and DR4 haplotypes. Linkage analysis allowing for gametic disequilibrium reveals no recombination in pedigrees with a DR3/DR4 propositus, but spurious recombination in the remaining pedigrees. This evidence favors interaction of unlinked IDDM determinants to produce affection in a small proportion of heterozygotes for an HLA-linked determinant. Partition of data by HLA type of the propositus (ideally by DR and the complement types jointly) is a powerful method to resolve etiological heterogeneity for HLA-associated diseases.

Adult↗
PubMed1982

Evidence for an autosomal recessive gene regulating the persistence of the insulin response to glucose in man.

The significance of genetic factors for insulin release after glucose infusion was studied in 155 nuclear families of which 59 were control families and 96 had been ascertained through a parent with onset of diabetes after 30 years of age. Fasting insulin and glucose as well as three principal components of the insulin and glucose curves were submitted to path analysis and complex segregation analysis. The three principal components were considered to reflect the magnitude, the degree of response and the persistence of the curves. The genetic heritability of the insulin variables varied between 0.47-0.93 and that of the glucose variables between 0.20-0.54. There were considerable intergenerational differences in the genetic heritability for the persistence of the glucose curve and for the degree of response and persistence of the insulin curve. The cultural heritability was found to be of minor importance, while the non-transmitted sibling environment was large. There was significant evidence for a major locus for the persistence of the insulin curve. The best fit was for a completely recessive autosomal gene with the gene frequency 0.21. The phenotype distribution of this variable showed significant kurtosis which could simulate a major locus. However, the significant evidence for such a locus remained after an analysis using partial quantitation. The diabetics were significantly different from the non-diabetics for all the variables studied, but a complete discrimination between the diabetics and non-diabetics could not be obtained. There was no significant difference between the children of the diabetics and non-diabetics for any of the variables studied.

Adult↗
PubMed1982

Genetic studies of insulin-dependent diabetes mellitus: segregation and linkage analyses.

The inclusion of HLA data in genetic studies of insulin-dependent diabetes mellitus (IDDM) has not led to conclusive segregation models for IDDM so far. As a new approach, we first applied complex segregation analysis, independently of HLA data, to two combined Danish family materials. Then the best fitting segregation model was entered into linkage analysis of a third material, including family as well as HLA data. The best solution obtained in the segregation analysis was a mixed model, including an intermediate gene, which on the penetrance scale acts as a recessive, together with a polygenic component. The linkage analysis showed an overall recombination fraction of 0.0417 with high coupling frequencies for the HLA-DR3 and HLA-DR4 alleles and the putative disease susceptibility gene. However, when the pedigrees were divided according to whether or not the proband had the heterozygous HLA-phenotype DR3/DR4, a maximum likelihood ratio test for heterogeneity was significant, with estimated recombination fractions of 0.0 and 0.0963 in HLA-DR3/DR4 pedigrees and the remaining pedigrees, respectively. In total, we found convincing evidence that two familial factors contribute to IDDM: a locus within HLA, which very well may be DR; and an unlinked mechanism which is unimportant for HLA-DR3/DR4 but simulates recombination. If confirmed, this conclusion has important implications for further genetic studies of IDDM and complex segregation analyses of family materials sampled according to criteria which include HLA data of the probands are highly needed.

Adolescent↗
PubMed1981

A girl with an interstitial deletion of the short arm of chromosome 3 studied with a high-resolution banding technique.

A girl with delayed growth in body height and weight, retarded psychomotor development, facial dysmorphism, high-arched palate, extension defects of elbows, and a probable hearing impairment is presented. A chromosome investigation by both conventional and high-resolution banding techniques revealed an apparently pure interstitial deletion of the proximal segment of the short arm of chromosome 3 (46,XX,del(3) (p11p14.2) de novo). The paternal karyotype is 47,XYY. The clinical features of the patient are compared with those of two previously reported cases in the literature with an interstitial 3p deletion.

Abnormalities, Multiple↗