The genetic background of anticipation.
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Age of Onset↗
Biomedical subjects
P Teisberg
Publications and source records attributed to P Teisberg.
Disease caused by expanding genes.
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Female↗
Genetics of non-insulin-dependent diabetes mellitus (NIDDM)
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Age of Onset↗
Linkage and association studies with C8A and C8B RFLPs on chromosome 1.
Linkage relations for the C8A and C8B BamHI RFLPs have been investigated. A peak lod score of 4.52 at recombination fraction zero was obtained between the two C8 genes. Combined with our previously obtained linkage data (Rogde et al. 1986) the maximum lod score is 7.53 at recombination fraction zero. The compiled C8-PGM1 linkage data from this and the previous study gave a maximum lod score of 22.02 at recombination fraction 0.11 (0.07-0.16) with no sex difference. A chromosome 1p reference marker, D1S57, has been applied in this linkage study. A maximum lod score of 5.06 between the C8 cluster and D1S57 at theta = 0.18 (0.11-0.28) was recorded. The linkage analyses and triply informative families gave evidence that the C8 loci are situated about halfway between PGM1 and D1S57 on the short arm of chromosome 1. There was no evidence of allelic association between the C8A and C8B BamHI RFLPs in 62 unrelated haplotypes.
Chromosome Mapping↗
Haptoglobin subtypes in Norway and a review of HP subtypes in various populations.
Isofocusing and immunoblotting of reduced serum samples identify the common haptoglobin alpha-chain variants 1S, 1F, 2FS, 2SS, 2FF, 3, as well as several rare alpha- and beta-chain variants. The gene frequencies found in 6,668 unrelated persons involved in Norwegian paternity cases were: HP*1S: 0.22, HP*1F: 0.16, HP*2FS: 0.58, HP*2SS: 0.04, HP*2FF: 0.004, HP*3: 0.0004, other HP* alpha variants: 0.0004, HP* beta variants: 0.0008. The corresponding gene frequencies in 153 unrelated Norwegian Saamis (Lapps) were: HP*1S: 0.19, HP*1F: 0.07, HP*2FS: 0.70, HP*2SS: 0.04. Norwegians and Norwegian Saamis differed both in phenotype and allele distribution. An earlier Norwegian population study has shown a lower HP*1 frequency in the north than in the south. This regional difference in haptoglobin gene distribution was reflected in the present material as a lower 1F frequency, indicating a Saamish influence in northern Norway. Furthermore, the relatively low 2FF frequency in the north coincides with the lack of observed 2FF genes in the Saamish population. Non-Scandinavians involved in Norwegian paternity cases did not differ from the rest of the material. A review of published haptoglobin gene frequencies shows the 1F frequency to be a good indicator of ethnic origin, and that 2FF and 2SS frequency determinations may also be valuable in genetic population studies.
Alleles↗
Use of DNA amplification (PCR) and direct DNA sequencing in the characterization of C4 alleles.
A procedure for detailed characterization of individual C4 alleles has been developed. DNA containing the two polymorphic clusters of C4 was amplified in the polymerase chain reaction (PCR). Direct DNA sequencing of amplified DNA was then performed by a modification of previously described techniques. The results were confirmed by M13 sequencing. Single C4A3 and C4B1 allele sequences were in accordance with previous reports. An individual typed C4A3B1 revealed double bands in the autoradiogram in the positions corresponding to the polymorphic nucleotides. We did not find the reported thymine in position 3641 specific for the C4A4 allele in an individual typed C4A4B2.
Alleles↗
Genetic aspects of complement component C8 in Norwegian meningococcal disease patients.
Sera from 85 consecutive systemic meningococcal disease patients and 203 matched control individuals were C8 typed. In the patient group, one C8B deficient individual was discovered; none in the control group. No case of C8A deficiency was encountered. The material was collected during a period of epidemic meningococcal disease in Norway, mainly due to group B organisms. C8A and C8B phenotype distributions were not significantly different in the two groups. This indicates that no particular C8 type (apart from deficiency) predisposes for meningococcal disease. Neither is there any evidence of over-representation of heterozygous deficiency among meningitis patients. The C8B deficient individual and his family were studied. Tests for haemolytic complement were normal in all members except for the proband. Electrophoretic C8 patterns seemed to be slightly weaker in the heterozygously C8B deficient individuals than in persons with 2 normal C8B genes. DNA from the family members were studied with regard to a restriction fragment length polymorphism (RFLP) for the C8B gene. All exhibited the same pattern, indicating that the C8B deficiency is not due to a major deletion in the C8B gene.
Complement C8↗
[Use of modern gene technology in forensic medicine].
Modern DNA technology has had a great impact upon the practice of forensic genetics. Recently developed methods have disclosed different types of genetic variability in human DNA. Typing of genetic DNA polymorphisms based on point mutations represents an alternative to the blood and protein systems developed before. However, the discovery of the so-called hypervariable regions (HVR) in the genome, which represent grossly rearranged areas of DNA, has, revolutionised the field. "Fingerprints", nearly specific for each individual in the population, can be developed by employing specific probes, restriction enzymes and Southern blot technique. We present some results of the application of these techniques in criminal cases investigated at the Institute of Forensic Medicine in Oslo. In future, the sensitivity of the methods may be increased through amplification procedures (PCR reaction).
DNA Probes↗
A BamH1 RFLP of the C8B gene.
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Chromosomes, Human, Pair 1↗
Genetic analysis of C4 polymorphism by use of DNA amplification (PCR), allele-specific oligonucleotide probes and allele-specific restriction enzymes.
In vitro DNA amplification allows multiplication of selected gene segments thereby improving the sensitivity in DNA analysis. Different allelic variants in the amplified DNA may be disclosed either by subsequent hybridization with allele-specific oligonucleotides or by subsequent allele-specific digestion with selected restriction endonucleases, followed by separation in agarose gel electrophoresis. The genes that code for human complement component C4 are polymorphic. Presently we demonstrate that allelic differences in C4, involving one base pair only, can be efficiently identified in the amplified DNA by each of the two techniques. A combination of both techniques may also be employed. The DNA amplification procedure may give access to selected 'haploid' fragments for individual DNA studies.
Alleles↗
C8A and C8B polymorphisms in Norwegians and Norwegian lapps.
C8 inheritance patterns in 364 mother-child pairs formed the basis for evaluation of the existence of silent alleles (null alleles) in the genes determining the two known polymorphic C8 systems. While evidence for such alleles was not found in C8A (alpha-gamma complex), two observations of null allele segregation in C8B (beta chain) indicate a C8BQ*0 allele frequency of about 0.07. Two population samples comprising 150 Lappish and 1,264 non-Lappish Norwegians were examined for phenotype distributions in C8A and C8B. The phenotype distributions were mainly in accordance with the expected Hardy-Weinberg distribution. The results for C8A indicated simple, codominant inheritance of two frequent and several rare alleles. Allele frequencies were similar in the two populations. The C8A B gene frequency in Norwegians was significantly lower than that in FRG and higher than that in Negroes. C8B allele frequencies were also calculated from gene counts in the population material, but with due corrections for the C8BQ*0 frequency observed in the mother-child material.
Alleles↗
Forensic aspects of haptoglobin: electrophoretic patterns of haptoglobin allotype products and an evaluation of typing procedure.
A procedure used for haptoglobin (Hp) typing in paternity cases has been evaluated. All serum samples have been subtyped with a one-dimensional isoelectric focusing/immunoblotting method, and samples with rare or questionable patterns have been further examined by two-dimensional electrophoresis with isoelectric focusing in the first dimension followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second dimension. The electrophoretic Hp-patterns of common and rare alpha- and beta-chain variants are shown, including allotype patterns of two new beta-chain variants and three new alpha-chain variants. Retyping of nearly 2000 individuals at intervals between 1 to 12 months revealed a typing error frequency of about 0.3%, which is considered acceptable, provided new blood samples are required in every case of paternity exclusion. Comparison of typing results obtained with the present procedure and with routine starch gel electrophoresis in more than 5000 serum samples gave conflicting results in 6 samples. The sensitivity of the described one-dimensional subtyping method was slightly better than that of starch gel electrophoresis. In 4110 unrelated individuals, involved in cases of disputed paternity the Hp 2SS 0.038, Hp 2FF 0.004, and Hp 3 (Johnson) 0.0005. These allele frequencies give a theoretical paternity exclusion rate of 32.5%, which is in accordance with the observed rate in 2200 paternity cases with more than 600 non-fathers. It is concluded that the present procedure represents a definite improvement for Hp subtyping in practical paternity diagnostics. Preliminary results with retyping of weak Hp patterns using a staining technique involving the biotin/avidin complex indicate that the sensitivity of the one-dimensional subtyping method may be substantially increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrophoresis, Gel, Two-Dimensional↗
Restriction fragment length polymorphisms of the complement component C4 loci on chromosome 6: studies with emphasis on the determination of gene number.
Restriction fragment length polymorphisms of the C4 region of human chromosome 6 have been studied in family material where the haplotypes are defined with regard to other genetic markers in this region. Employing one near full-length C4 probe and the combination of BglII and XbaI enzymes, five different C4 genes were characterized. Studies of the segregation of DNA patterns in families made possible the reliable determination of DNA C4 haplotype pattern including gene number. In the total material of 76 haplotypes, 13 different types with regard to number and/or DNA type of C4 gene(s) were encountered. Twelve of the haplotypes had one C4 gene only, 58 had two genes, while 6 had three C4 genes. This fits fairly well with the hypothesis that the one- and three-gene haplotypes have originated through unequal crossing-over between chromosomes carrying duplicated C4 genes.
Blotting, Southern↗
Identification in blood stains through DNA typing with C4 and HLA-DR probes.
A restriction fragment length polymorphism analysis using double digestion of DNA preparations with XbaI and BglII restriction enzymes and hybridization with C4 and HLA-DR probes is described. The typing conditions selected reveal extensive individual variation in both C4 and DR gene regions. In our panel of 46 unrelated individuals, 37 different phenotypic patterns were recognized when both probes were used, and preliminary discriminative power values of 0.865 and 0.914 were calculated for C4 and DR beta, respectively. The probability of a chance match using both systems is probably about 1.5.10(-2). The potential of this method for individual identification of blood stains was demonstrated on DNA prepared from 6-month-old dried blood stains from seven panel individuals. The seven individuals were all identified when comparing stain DNA patterns with panel control patterns. No RFLP pattern changes were observed following storage of blood stains. Based on these experiments with C4 and DR beta DNA typing under laboratory conditions, it is concluded that DNA typing with such probes may become a powerful tool in future stain identification analyses.
Blood Grouping and Crossmatching↗
A comparative study on the effect of atenolol and labetalol on exercise capacity and lipid serum levels in essential hypertension.
Exercise performance was examined in 30 hypertensive subjects (mean age 43.2 +/- 5.4 years) in WHO group I-II, allocated to placebo, atenolol and labetalol treatment during a 3 X 12 weeks' exercise training period. Total work did not show any differences between the placebo and the two treatment periods. Compared to placebo, total cholesterol was reduced by 4.6% (p less than 0.04) in the labetalol and 3.1% (NS) in the atenolol period. Systolic and diastolic blood pressure were significantly reduced both at rest (p less than 0.01) and during exercise (p less than 0.01) in the two drug treatment periods compared to placebo.
Adult↗
Effect of exercise training in patients with essential hypertension.
After 12 weeks of regular exercise training in 34 patients with moderate essential hypertension, supine systolic blood pressure at rest decrease from 152 +/- 2 (means +/- SEM) to 149 +/- 2 mmHg (p less than 0.05), and diastolic blood pressure from 106 +/- 1 to 102 +/- 1 mmHg (p less than 0.001). At corresponding submaximal exercise levels, diastolic blood pressure also decreased significantly from 110 +/- 2 to 98 +/- 3 mmHg (p less than 0.001), but no significant reduction in systolic blood pressure was observed. Heart rate at the same submaximal work load was significantly reduced (p less than 0.01). This data shows that exercise training might have blood pressure lowering effect in patients with moderate essential hypertension, and might in some patients be an alternative to pharmacological treatment.
Adult↗
The C8A and C8B loci are closely linked on chromosome 1.
Close linkage was demonstrated between the loci governing the polymorphisms of complement component C8 alpha-gamma (C8A) and beta (C8B). Both C8 loci were linked to the chromosome 1 marker loci PGM1 and Rh. The distance between the two C8 loci and PGM1 appeared identical in males and females. A female/male ratio of 1.6 was observed between the two C8 loci and Rh. No evidence for linkage between the C8 loci and Fy was found. Preliminary results of this study were presented at the Eighth International Workshop on Human Gene Mapping, Helsinki, August 1985 (Rogde et al. 1985b).
Chromosomes, Human, Pair 1↗