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Biomedical subjects

L Iselius

Publications and source records attributed to L Iselius.

At least 55 records · Page 3Linked to original sources
PubMed1991

Genetic epidemiology of breast cancer in Britain.

A complex segregation analysis was conducted on two British series (one consecutive series of probands with breast cancer and one series ascertained through a normal consultand). Altogether there were 1248 nuclear families with breast cancer. A dominant gene with a frequency of 0.003 giving a lifetime penetrance of 0.83 is favoured. Ovarian, endometrial and cancers associated with the SBLA syndrome, as well as benign breast disease, were significantly more common in familial breast cancer than in families of single cases. Probands in families with more than one individual with breast cancer were non-significantly younger than isolated probands.

Adult↗
PubMed1991

Von Hippel-Lindau disease: a genetic study.

Genetic aspects of von Hippel-Lindau (VHL) disease were studied in familial and isolated cases. Complex segregation analysis with pointers was performed in 38 kindreds with two or more affected members. Dominant inheritance with almost complete penetrance in the highest age classes (0.96 at 51 to 60 and 0.99 at 61 to 70 years) was confirmed and there was no evidence of heterogeneity between families ascertained through complete and incomplete selection. The point prevalence of heterozygotes in East Anglia was 1.89/100,000 (1/53,000) persons with an estimated birth incidence of 2.73/100,000 (1/36,000) live births. Reproductive fitness was 0.83. Direct and indirect estimates of the mutation rate were 4.4 (95% CI 0.9 to 7.9) x 10(-6)/gene/generation and 2.32 x 10(-6)/gene/generation respectively. There was no significant association between parental age or birth order and new mutations for VHL disease.

Adult↗
PubMed1990

Leukaemia and transient leukaemia in Down syndrome.

We have reviewed 215 published cases of leukaemia and transient leukaemia in Down syndrome. There is an over-representation of mosaic trisomy 21, possibly the result, at least in part, of a survival effect. The most intriguing observation is a bimodal distribution of maternal age, produced largely because cases with true leukaemia have a significantly higher maternal age than cases with transient leukaemia (33.5 versus 29.5 years). In conjunction with evidence that meiosis I nondisjunction is infrequent in transient leukaemia, this suggests different mechanisms for the etiology of leukaemia and transient leukaemia, and favours a locus predisposing to transient leukaemia proximal to the centromere on the long arm of chromosome 21.

Adolescent↗
PubMed1990

Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations.

European data on the polymorphic metabolism of debrisoquine, sparteine, dextromethorphan and mephenytoin have been collected. No significant difference in phenotype frequencies was found between the separate series for debrisoquine, sparteine and dextromethorphan, which supports the claim that these probe drugs reflect the same enzyme polymorphism. The mean frequency of the phenotype slow debrisoquine metaboliser was 7.65% based on 5005 determinations. The overall mean reflecting all three drugs and 8764 determinations was 7.40%. This is consistent with a gene frequency of 0.27 (95% confidence interval 0.26-0.28). The overall mean of the phenotype slow metaboliser of mephenytoin was 3.52% corresponding to a gene frequency of 0.19 (confidence interval 0.17-0.20). The incidence of slow metabolism of debrisoquine and possibly also of S-mephenytoin was homogeneous in the samples from European populations. This is of considerable interest as interethnic differences are now being found both in the phenotypic characters as well as the genotypes of polymorphic drug oxidation.

Debrisoquin↗
PubMed1990

A linkage study of a large pedigree with X linked centronuclear myopathy.

Centronuclear myopathy (CNM) is a muscle wasting disorder that occurs in three distinct forms. Previous studies have shown linkage between the X linked form of the disease and the Xq28 probes ST14, DX13, and F8C. Our study on a previously unreported, three generation, X linked CNM family confirms linkage between these markers and the CNM locus (Z = 3.21, theta = 00). However, results from the laboratory of J-L Mandel (Samson and Hanover, personal communication) on a number of X linked CNM families exclude genetic linkage from the region Xq26-qter, suggesting genetic heterogeneity in this condition.

Cell Nucleus↗
PubMed1990

Mapping of the gene for X-linked amelogenesis imperfecta by linkage analysis.

X-linked Amelogenesis imperfecta (AI) is a genetic disorder affecting the formation of enamel. In the present study two families, one with X-linked dominant and one with X-linked recessive AI, were studied by linkage analysis. Eleven cloned RFLP markers of known regional location were used. Evidence was obtained for linkage between the AI locus and the marker p782, defining the locus DXS85 at Xp22, by using two-point analysis. No recombination was scored between these two loci in 15 informative meioses, and a peak lod score (Zmax) of 4.45 was calculated at zero recombination fraction. Recombination was observed between the more distal locus DXS89 and AI, giving a peak lod score of 3.41 at a recombination fraction of .09. Recombination was also observed between the AI locus and the more proximal loci DXS43 and DXS41 (Zmax = 0.09 at theta max = 0.31 and Zmax = 0.61 at theta max = 0.28, respectively). Absence of linkage was observed between the AI locus and seven other loci, located proximal to DXS41 or on the long arm of the X chromosome. On the basis of two-point linkage analysis and analysis of crossover events, we propose the following order of loci at Xp22: DXS89-(AI, DXS85)-DXS43-DXS41-Xcen.

Amelogenesis Imperfecta↗
PubMed1989

Complex segregation analysis for a three-allele locus: experience from an analysis of acid phosphatase activity.

A complex segregation analysis of acid phosphatase activity in 50 British families showed that the essential features of the acid phosphatase polymorphism, i.e., a major gene with three alleles, is retrieved by using the biallelic mixed model. The estimates of gene frequency and displacement obtained from segregation analysis were in agreement with those obtained from electrophoretic studies. In addition, there was evidence for a multifactorial component.

Acid Phosphatase↗
PubMed1989

Sjögren-Larsson syndrome in Sweden: distribution of the gene.

The distribution of carriers of the gene for Sjögren-Larsson syndrome in Sweden suggests a center of dispersion in the county of Västerbotten in Northern Sweden. The origin of the spread of the gene can be traced back at least 700 years.

Gene Frequency↗
PubMed1989

The distribution of the gene for the juvenile type of Gaucher disease in Sweden.

A study of 30 Swedish families with the Norrbottnian type of Gaucher disease provides evidence for two clusters of the gene, one close to Overkalix in the northern part of the county of Norrbotten and the other in the vicinity of Arvidsjaur in the southern part of the same county. The gene for Gaucher disease in Overkalix appeared later than that in Arvidsjaur. A founder moving from Arvidsjaur to Overkalix during the seventeenth century or two different mutations are the most likely explanations of this finding.

Female↗
PubMed1989

Evidence for a major additive gene in ulcerative colitis.

Complex segregation analysis of 124 families with ulcerative colitis with two or more affected individuals suggests a rare additive major gene causing the disease with about 20% affected among the heterozygotes for the gene. There was no evidence for multifactorial inheritance.

Colitis, Ulcerative↗
PubMed1988

A twin study of amino acid concentrations in cerebrospinal fluid.

The concentrations of amino acids in the cerebrospinal fluid (CSF) were measured in pairs of healthy mono- and dizygotic twins. Intraclass correlations were calculated. Genetic and cultural heritabilities were estimated using a path analytical model. CSF levels of glycine, tyrosine and arginine were shown to be influenced by genetic factors. Genetic variation was also shown for serine, alpha-aminobutyrate and leucine. The results were compared with results from a genetic analysis of the amino acids in serum.

Adolescent↗
PubMed1988

A linkage study of the locus for X-linked Charcot-Marie-Tooth disease.

A large family with Charcot-Marie-Tooth disease, showing a probable X-linked incomplete dominant inheritance, was studied by linkage analysis. Results, obtained by the use of X chromosome specific DNA probes of known regional location, suggest that the disease locus is linked to the DXYS1 locus (z = 2.59 at theta = 0.00) and to the DXS14 locus and, places the disease locus between the DXYS1 locus and the DXS14 locus, near the centromere of the X chromosome. Together with the published data, a distance of 13 cM (z = 6.95) was assessed between the disease locus and the DXYS1 locus.

Charcot-Marie-Tooth Disease↗
PubMed1987

Genetic and cultural inheritance of plasma fibrinogen concentration.

Genetic and cultural heritability of plasma fibrinogen concentration was estimated by path analysis with environmental indices in 85 families identified by means of probands with early myocardial infarction and in 85 families randomly selected from the general population. A substantial proportion of the variance of the plasma fibrinogen level, 51%, was accounted for by genetic heritability, whereas the cultural heritability was negligible. No intergenerational differences were indicated in genetic or cultural heritability. The combined effect of obesity and smoking was found to explain 3% of the variance of the plasma fibrinogen level. The demonstration of such substantial genetic control further supports the view that plasma fibrinogen is a primary risk factor for CHD rather than a reflection of the severity of manifest disease.

Adult↗
PubMed1986

Genetic and cultural inheritance of serum lipids, low and high density lipoprotein cholesterol and serum apolipoproteins A-I, A-II and B.

The genetic and cultural heritability of serum cholesterol and triglyceride concentrations, as well as of the concentrations of low and high density lipoprotein cholesterol and serum apolipoproteins A-I, A-II and B, were estimated by path analysis in families selected through probands with premature myocardial infarction and in families randomly selected from the general population. Genetic heritability was high for serum cholesterol (0.64) and low density lipoprotein cholesterol (0.67) concentrations, whereas it was lower for high density lipoprotein cholesterol level (0.42). Cultural inheritance was of less importance than genetic inheritance for all cholesterol variables. For serum triglyceride concentration genetic (0.33) and cultural (0.23) heritability was of similar significance. The results for serum apolipoproteins A-I and A-II parallelled those for HDL cholesterol. A marked intergenerational difference was found in the genetic heritability for apolipoprotein B concentration. The parental genetic heritability was 0.14, whereas the genetic heritability was 0.51 among siblings.

Adult↗
PubMed1986

Concentrations of monoamine metabolites in the cerebrospinal fluid of twins and unrelated individuals--a genetic study.

The concentrations of the major monoamine metabolites, homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF), of platelet monoamine oxidase (MAO) and of dopamine beta-hydroxylase (DBH)-activity in serum and CSF were determined in pairs of healthy mono- and dizygotic twins, brothers and unrelated individuals. Intraclass correlations were calculated for each category of pairs. Of the monoamine metabolites, only MOPEG was found to be under any major genetic influence. Genetic heritability for MOPEG was 0.74 with no evidence of cultural heritability or environment common to twins. For HVA and 5-HIAA, a familial influence was found, where the cultural heritability was higher than the genetic. As in previous studies of MAO in blood platelets and of DBH activity in serum, there was strong evidence for a genetic component. The genetic heritability for MAO was 0.78. For DBH in serum the genetic component was 0.98, and for DBH in CSF, 0.83. The demonstration of a familial influence on 5-HIAA and HVA in CSF requires a more detailed analysis of the character of such environmental and genetic influences, using more direct techniques.

Adolescent↗