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A Arnason

Publications and source records attributed to A Arnason.

At least 37 records · Page 2Linked to original sources
PubMed1990

Analysis of the C4 genes in baleen whales using a human cDNA probe.

We have used a human C4 cDNA probe to investigate the complement component C4 gene in four members of the family Balaenopteridae: fin whale (Balaenoptera physalus), sei whale (B. borealis), minke whale (B. acutorostrata), and bryde's whale (B. edeni). Restriction mapping of genomic DNA from the first three species suggests the presence of only one locus in these species, and also shows that the C4 genes in the three species are very similar. We have used 14 restriction endonucleases to investigate the restriction fragment length polymorphism (RFLP) of fin whales, 13 enzymes for sei whales, and 8 enzymes for the minke whale. No polymorphism was seen in DNA from the five minke whale samples, but Rsa I and Taq I restriction enzymes gave polymorphism in fin and sei whales whereas Hind III and Msp I restriction enzymes showed polymorphism in sei whales only. Only one bryde's whale sample was available for investigation. The study of DNA available from mother-fetus pairs from the two polymorphic species demonstrated a simple, two-allele transmission of RFLP alleles.

Animals↗
PubMed1990

The first Icelandic family with X-linked agammaglobulinaemia: studies of genetic markers and immune function.

This paper describes studies of genetic markers and immune functions in the first Icelandic family identified with X-linked agammaglobulinaemia (X-LA), including three affected brothers. The eldest brother was diagnosed at the age of 9 in 1963. He suffered repeated infections and died at the age of 23. The other two affected brothers, diagnosed at 6 years and 1 year of age, are alive and well on immunoglobulin replacement therapy at the ages of 32 and 24. All were typed for HLA, complement, and various other markers. Pedigree analysis suggests an X-linked segregation of the disease. Their serum IgG is maintained at normal levels on therapy. Several parameters of immune function were studied. The following results were obtained for the X-LA brothers: B cells are absent in their peripheral blood samples. T-cell numbers are normal, but monocytes are increased in numbers and activity. No immunoglobulin production could be elicited in vitro with PWM and no cells containing cytoplasmic Ig were detectable among PWM-stimulated blasts. Nevertheless the proliferative response was particularly vigorous, but the responding cells were shown to be exclusively T cells. No blast transformation could be achieved with EB virus. NK-cell activity was normal/high normal. Other cell-mediated immune functions were normal. In conclusion our data indicate that the differentiation of B cells is blocked in the two surviving X-LA brothers. They have survived for a longer time and in better health than is generally reported. Early diagnosis and adequate replacement treatment with Ig is clearly crucial. Vigorous non-specific immune mechanisms may help to compensate for the defective specific immunity.

Agammaglobulinemia↗
PubMed1989

Limited MHC polymorphism in whales.

Little is known about disease and genetic variation in aquatic mammalian species such as whales. In this paper human HLA class I and class II probes were used to study major histocompatibility complex (MHC) genes from two species of whale: Fin (Balaenoptera physalus) and Sei (B. borealis). Stronger signals were obtained on whale than on equivalent concentrations of mouse DNA. Evidence was obtained for several DRB-related genes, a DNA genes, one DQA gene, and multiple class I genes in whales. Interestingly, the whale genes, from the small panel studied, were less polymorphic than those of humans or mice. The aquatic environment of this mammalian species may be a unique factor in shaping its immune response through the MHC.

Animals↗
PubMed1989

The saga of cystatin C gene mutation causing amyloid angiopathy and brain hemorrhage--clinical genetics in Iceland.

Firstly, we review investigations of hereditary cystatin C amyloid angiopathy, which is caused by a mutation in the cystatin C gene. Symptoms of brain haemorrhages, which lead to death in young adults, are the hallmark of this disorder. The mutation can now be detected by the RFLP method using Alu I restriction enzyme and cystatin C cDNA probe. Secondly, we give an overview of other clinical genetic studies in Iceland with emphasis on activities initiated or sponsored by the Genetical Committee of the University of Iceland. The list of references covers most publications on genetic studies of Icelanders.

Amyloidosis↗
PubMed1989

X-linked cleft palate and ankyloglossia in an Icelandic family.

Information was available on 293 family members and spouses of seven generations in an Icelandic family with high frequency of cleft of secondary palate and ankyloglossia. The authors have personally investigated 182 individuals in generations IV-VII and have drawn blood from over 100 members for genetic marker studies. The senior author, Dr. Björnsson, has operated on two-thirds of the affected individuals. Twenty-six family members had cleft palate (CP) and, of these, 19 (17 male and two females) had ankyloglossia as well (CP + A). Twenty females and one male had only ankyloglossia (A). All mothers in one of two branches of the family who had sons with CP + A had ankyloglossia themselves. This was not the case in the other branch, in which the mothers of affected sons were themselves unaffected. Fathers affected with CP, CP + A, or high vaulted palate (HVP) never had affected sons. As reported earlier, the condition has been mapped to the q13-q21 region of the X chromosome using restriction fragment length polymorphism (RFLP) techniques (Moore et al, 1987). Our conclusion is that this midline defect is X-linked but varies in the severity of expression.

Chromosome Mapping↗
PubMed1989

Study of restriction fragment length polymorphism in the cystatin C gene of elderly patients with dementia and aged Down's syndrome patients.

Using a full length cystatin C cDNA probe and the Alu I restriction enzyme a total of 33 patients with senile dementia, Alzheimer type and 31 Down's syndrome patients have been investigated for the presence of the 630 bp Alu I restriction fragment length polymorphism in the cystatin C gene detected in Icelandic patients with hereditary cystatin C amyloid angiopathy. Results showed that all the patients had normal cystatin C fragment length of 600 bp.

Adult↗
PubMed1989

Mutation in the cystatin C gene causes hereditary brain hemorrhage.

Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder leading to massive brain hemorrhage and death in young adults (Jensson et al., 1987). A variant of a potent inhibitor of cysteine proteinases, cystatin C (Barrett et al., 1984), is deposited as amyloid fibrils in the cerebral arteries of the patients (Ghiso et al., 1986). We have used the full length cystatin C cDNA probe (Abrahamson et al., 1987) to demonstrate a mutation in the codon for leucine at position 68, which abolishes an Alu I restriction site in cystatin C gene of the HCCAA patients. The Alu I marker has been used to show that this mutation is transmitted only in the affected members in all eight families investigated, proving that the mutated cystatin C gene causes HCCAA. This DNA marker will be useful for the diagnosis of HCCAA in patients, asymptomatic affected individuals and also for pre-natal diagnosis. HCCAA is the first human disorder known to be caused by an abnormal gene for a cysteine proteinase inhibitor.

Amyloidosis↗
PubMed1988

Mutation in cystatin C gene causes hereditary brain haemorrhage.

Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder in which a cysteine proteinase inhibitor, cystatin C, is deposited as amyloid fibrils in the cerebral arteries of patients and leads to massive brain haemorrhage and death in young adults. A full length cystatin C cDNA probe revealed a mutation in the codon for leucine at position 68 which abolishes an Alu I restriction site in the cystatin C gene of HCCAA patients. The Alu I marker has been used to show that this mutation is transmitted only in affected members of all eight families investigated, and that the mutated cystatin C gene causes HCCAA.

Cerebral Hemorrhage↗
PubMed1988

The application of molecular genetics to detection of craniofacial abnormality.

Congenital malformations such as secondary cleft palate can be exclusively monogenic or polygenic, but most cases have a multifactorial origin involving both environmental and genetic factors, making genetic analysis difficult. The new techniques of molecular genetics have allowed the successful chromosomal localization of mutant genes in disorders that show a simple Mendelian segregation, whether autosomal dominant (e.g. Huntington's disease), autosomal recessive (cystic fibrosis) or X-linked (Duchenne muscular dystrophy). Recently, a large Icelandic family (over 280 members) with X-linked secondary cleft palate and ankyloglossia (tongue-tied) has been used as a model to localize the mutant gene associated with this craniofacial clefting. The gene has been sub-chromosomally localized to Xq13-q21.1, using anonymous probe DXYS1; a LOD score of 3.07 was obtained. We are preparing cosmid libraries from DNA from mouse cell lines containing only the relevant part of the human X chromosome, introduced by chromosome-mediated gene transfer. Cosmids that contain human X-chromosome sequences will be isolated and analysed for overlapping sequences and RFLPs (restriction fragment length polymorphisms) and the regions further defined by pulsed-field gel electrophoresis and the identification of coding sequences. This should give data on the location and structure of a gene involved in the craniofacial development of the human palatine shelves. This gene, and its protein product, will identify one component of the pathway that causes nonfusion of the palate. In the long term, the understanding of the expression of this sex-linked gene for secondary cleft palate and ankyloglossia will provide a model for the molecular identification of other genes regulating processes in craniofacial development whose expression is hidden in phenotypic, polygenic complexity.

Cleft Palate↗
PubMed1987

Gene organization of haplotypes expressing two different C4A allotypes.

The gene organization of C4 haplotypes expressing two different C4A allotypes with a C4B null allele (C4A3A2BQ0 and C4A3A6BQO) was studied using Southern blot analysis with cDNA probes and restriction enzymes which give C4A and C4B locus-specific restriction fragments. These haplotypes were shown to have both a C4A and a C4B locus present, suggesting that the C4B locus expresses a C4A protein. The finding of a 21-OH A and a 21-OH B gene on the C4A3A6BQO haplotype further suggests that this haplotype has the common gene organization C4A, 21-OH A, C4B, 21-OH B. A model explaining C4 null alleles on haplotypes found to have two C4 loci is presented.

Alleles↗
PubMed1987

Heterogeneity of human C4 gene size. A large intron (6.5 kb) is present in all C4A genes and some C4B genes.

In this article we present a study showing that the human C4 genes differ in length because of the presence or absence of a 6.5 kb intron near the 5' end of the gene. DNA from individuals of known HLA, factor B, and C4 haplotypes was analyzed for restriction fragment length polymorphism (RFLP) by Southern blot analysis with C4-specific cDNA probes. The RFLP patterns obtained showed that the C4 genes are either 22.5 kb or 16 kb in length. They are referred to as long and short C4 genes, respectively. A population study was carried out to examine the distribution of the gene size according to C4 allotypes and haplotypes. Long C4 genes included all C4A genes studied and also some C4B allotypes, e.g., B1 on most C4 A3B1 haplotypes. Similarly, C4B null genes were found to be of the long form. Other C4B allotypes tested were found to be coded for by short C4 genes, including B2, B1 in C4 A6B1 and C4 AQOB1 (with a single C4B gene haplotype).

Complement C4↗
PubMed1987

Left bundle branch block: prevalence, incidence, follow-up and outcome.

In a randomly selected population screening study of 8450 men and 9039 women 33 to 71 years of age conducted in Iceland in 1967-1977, 27 men and 17 women were found to have left bundle branch bock (LBBB). The prevalence of LBBB at that time was 0.43% for men and 0.28% for women. The incidence of LBBB was 3.2 per 10,000 per year for men and 3.7 per 10,000 per year for women. All except one of 37 alive patients with LBBB were examined in 1984 including chest X-ray, echocardiography and exercise testing (Bruce protocol). Eight men had had myocardial infarction (P less than 0.05), 12 had angina pectoris, 15 had hypertension, 7 had cardiomyopathy, 13 had primary conduction disease, and 3 had pacemakers. Five men and two women had died in comparison with 18 men and 1 woman in an age-matched control group of 176 people (P : ns). Three of 5 decreased LBBB men had cardiomyopathy at autopsy. Three men died suddenly. The two women died of noncardiac causes. Only one patient in the control group had cardiomyopathy (P less than 0.01). There was no significant difference in other cardiac diagnoses between the groups. Eleven LBBB women out of thirteen had a normal exercise duration (greater than or equal to 6 min) and 11/17 men exercised normally (less than or equal to 7 min). In comparison with the control group, the LBBB patients had an increased LV diameter 2.85 +/- 0.38 vs 2.58 +/- 0.38 cm m-2 body surface area (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Hereditary cystatin C (gamma-trace) amyloid angiopathy of the CNS causing cerebral hemorrhage.

Hereditary CNS amyloid angiopathy occurring in Icelanders is the first human disorder known to be caused by deposition of cystatin C amyloid fibrils in the walls of the brain arteries leading to single or or multiple strokes with fatal outcome. One or more affected members have been verified by histological examination in 8 families containing 127 affected. These originated from the same geographic area. Abnormally low value of cystatin C found in the cerebrospinal fluid of those affected can be used to support or make diagnosis of this disease, also in asymptomatic relatives. By amino acid sequence analysis the amyloid fibrils in the patients are found to be a variant of cystatin C (gamma-trace), a major cysteine proteinase inhibitor. The variant protein has an amino acid substitution (glutamine for leucine) at position 58 in the amyloid molecule. It is postulated that a point mutation has occurred leading to production of amyloidogenic protein causing the disorder.

Amyloid↗
PubMed1985

Rheumatic diseases in an Icelandic family. Clinical and immunological survey.

We have studied 192 members of a highly inbred Icelandic family with clustering of rheumatic diseases. Twelve consanguineous marriages are known in the family and 54 of 65 surviving offsprings of these (inbred group) were traced. Thirty-nine family members were affected by rheumatic diseases; 18 of them belonged to the inbred group. Eleven of 20 family members with rheumatoid arthritis (RA) came from the same inbred group. Eleven of the inbred group had a positive Rose-Waaler test for rheumatoid factor (RF) and the inbred group had significantly higher serum levels of IgG and IgM than an age and sex matched group from the family. Serum IgM RF was significantly associated with the age of the family members, but IgA RF and IgG RF did not show any such association. The possible role of recessive genes in the rheumatic diseases, as well as the inbreeding effect regarding certain extended HLA-complotypes is discussed.

Adolescent↗