Biomedical subjects
L E Holm
Publications and source records attributed to L E Holm.
A microsatellite linkage map of rainbow trout (Oncorhynchus mykiss) characterized by large sex-specific differences in recombination rates.
We constructed a genetic linkage map for a tetraploid derivative species, the rainbow trout (Oncorhynchus mykiss), using 191 microsatellite, 3 RAPD, 7 ESMP, and 7 allozyme markers in three backcross families. The linkage map consists of 29 linkage groups with potential arm displacements in the female map due to male-specific pseudolinkage arrangements. Synteny of duplicated microsatellite markers was used to identify and confirm some previously reported pseudolinkage arrangements based upon allozyme markers. Fifteen centromeric regions (20 chromosome arms) were identified with a half-tetrad analysis using gynogenetic diploids. Female map length is approximately 10 M, but this is a large underestimate as many genotyped segments remain unassigned at a LOD threshold of 3.0. Extreme differences in female:male map distances were observed (ratio F:M, 3.25:1). Females had much lower recombination rates (0.14:1) in telomeric regions than males, while recombination rates were much higher in females within regions proximal to the centromere (F:M, 10:1). Quadrivalent formations that appear almost exclusively in males are postulated to account for the observed differences.
Temporal changes in genetic variation of north European cattle breeds.
Temporal changes in genetic variation within and between 13 North European cattle breeds were evaluated using erythrocyte antigen systems and transferrin protein as genetic markers. Current data on allele frequency distributions of markers in large commercial and smaller endangered native cattle breeds were compared to data published during 1956 to 1975. Intrabreed genetic variation was quantified by conventional parameters (e.g. heterozygosity, average number of alleles per locus) and migration by the effective migration rate. The neighbour-joining dendrogram of relationships between old and present cattle populations was constructed using Nei's standard genetic distance. Variance effective population size was estimated from changes in allele frequencies over time. Comparison of old and new data indicated some significant changes in allele frequencies. In six of the breeds, a few low-frequency alleles in the old data were absent in the present samples. Heterozygosity remained stable in most breeds. The harmonic means for variance effective population size ranged between 30 and 257. Current results indicate that despite marked declines in total population sizes, North European native cattle breeds have retained a reasonably high genetic diversity. However, their genes contribute less than previously to genetic variation of Nordic production breeds. Commercial breeds do not appear to have a larger effective population size than native breeds. The present effective population sizes imply that Nordic breeds could have lost from 1 to 11% of their heterozygosity over a 20-40-year period.
Two polymorphic dinucleotide repeats in rainbow trout (Oncorhynchus mykiss).
Explore the source record for details and available documents.
Comparison of milk protein allele frequencies in Nordic cattle breeds.
Allele frequencies at four milk protein loci were studied in five modern and 17 old Nordic cattle breeds in order to reveal variants that are characteristic for these populations. The B allele of CSN3, which has been associated with improved manufacturing properties of milk, showed significantly lower frequencies in modern production breeds than in old breeds of interest for conservation purposes. Characteristic frequencies of CSN1S1 (C), CSN2 (A2) and CSN3 (B) were found in Icelandic cattle, Swedish Mountain cattle, Northern Finncattle and Western Fjord cattle, which indicate a common origin of these populations. Further comparisons of allele frequencies in old Nordic breeds suggest sorting of these breeds into two groups with a northern and southern geographic location.
Heterozygosity excess at the cattle DRB locus revealed by large scale genotyping of two closely linked microsatellites.
A method for MHC DRB typing in cattle based on two closely linked and highly polymorphic microsatellites is described. The two microsatellites DRBP1ms and DRB3ms are located in intron 2 of the corresponding DRB gene. The very strong linkage disequilibrium between the two loci made it possible to establish DRB microsatellite haplotypes. The typing results with this method on reference samples followed closely that obtained with RFLP and direct sequence analysis of DRB3 exon 2. The method is well suited for large scale genotyping and was successfully applied for typing more than 600 unrelated animals representing 23 breeds. The data were used to test whether the observed DRB allele frequency distributions were consistent with that expected for selectively neutral alleles in populations at mutation-drift equilibrium. A significant heterozygosity excess was detected and there was an obvious trend across breeds towards a more even allele frequency distribution than expected. The deviation may be due to balancing selection acting on the DRB locus or by recent population bottlenecks.
Low genetic variation in muskoxen (Ovibos moschatus) from western Greenland using microsatellites.
Muskoxen are large herbivores living in Arctic environments. Lack of genetic variation in allozymes has made it difficult to study the social and genetic structure of this species. In this study, we have tried to find polymorphic microsatellite loci using both cattle-derived microsatellite primers and primers developed from a genomic plasmid library of muskoxen. Only limited variation was found for both sets of microsatellite loci. We conclude that this consistent low genetic variation is probably due to demographic features of the muskoxen populations rather than to methodological constraints caused by the transfer of microsatellites between species.
Mortality after long-term exposure to radioactive Thorotrast: a forty-year follow-up survey in Sweden.
To evaluate temporal patterns of cause-specific mortality after long-term exposure to the alpha-particle-emitting contrast medium Thorotrast, we investigated a cohort consisting of 693 Swedish patients with neurological disorders who received Thorotrast during cerebral angiography, with follow-up ending in 1993. Standardized mortality ratios (SMRs) were calculated as the ratio of observed cases in the cohort to expected cases in the general population. Persons exposed to Thorotrast had significant excesses of all causes of death (SMR = 2.8; 95% CI 2.5-3.0), with similar increases noted for men and women. The largest risks were observed for deaths from hematological causes (SMR = 16.4; n = 8), cerebrovascular diseases (SMR = 10.1; n = 18), gastrointestinal disorders including liver cirrhosis (SMR = 5.2; n = 36), and tumors (SMR = 4.7; n = 187). There was a significant decrease in SMR with time since injection for cerebrovascular and circulatory diseases, indicative of the impact of underlying neurological disorders. In contrast, the SMR increased significantly with time for tumors and gastrointestinal diseases, suggestive of a detrimental effect of cumulative radiation dose. A significant dose-response relationship was found for all causes of death and malignant tumors among all age groups, and since SMR increased with time for the latter category, this is consistent with an effect of cumulative radiation exposure on cancer development. However, the findings should be treated with caution, since selection bias may have influenced some of the results.
Breast cancer risk after radiotherapy in infancy: a pooled analysis of two Swedish cohorts of 17,202 infants.
The incidence of breast cancer was studied in a cohort of 17,202 women irradiated for skin hemangioma in infancy at the Radiumhemmet, Stockholm, or the Sahlgrenska University Hospital, Gothenburg. A major part of the cohort had been treated with radium-226 applicators, and the mean absorbed dose to the breasts was 0.29 Gy (range <0.01-35.8 Gy). Two hundred forty-five breast cancers were diagnosed in the cohort during the period 1958-1993, and the standardized incidence ratio (SIR) was 1.20 (95% CI 1.06-1.36). Different dose-response models were tested, and a linear model gave the best fit. Neither age at exposure, breast dose rate, ovarian dose nor time since exposure had any statistically significant modifying effect, and breast dose was the only determinant of risk. The excess relative risk per gray (ERR/Gy) was 0.35 (95% CI 0.18-0.59), which is lower than in most other studies.
Lenticular opacities in individuals exposed to ionizing radiation in infancy.
Development of lens opacities and the measures taken to avoid them have clinical relevance in the fields of oncology, radiotherapy and radiation protection. The aim of this study was to correlate the prevalence of lenticular opacities in individuals exposed to ionizing radiation in childhood with radiation dose and other possible risk factors. Between 1920 and 1959, about 16,500 children (age <18 months) with skin hemangiomas were referred to Radiumhemmet, Karolinska University Hospital, 89% of whom were treated with radiotherapy. A total of 484 exposed individuals and 89 nonexposed controls participated in an ophthalmological examination. Lens opacities were found in 357 (37%) of the 953 lenses examined in the exposed persons. In contrast, lens opacities were observed in only 35 (20%) of the 178 lenses examined in the nonexposed control individuals. It is concluded that the increased prevalence of cortical and posterior subcapsular opacities is related to previous radiotherapy. Age at examination was the strongest modifier of risk. Children exposed to a lenticular dose of 1 Gy had a 50% increased risk (odds ratio 1.50; 95% confidence interval 1.10-2.05) of developing a posterior subcapsular opacity and a 35% increased risk of a cortical opacity (odds ratio 1.35; 95% confidence interval 1. 07- 1.69).
[How many X-ray examinations do patients tolerate? The National Institute of Radiation Protection's conclusions on the level of knowledge].
Explore the source record for details and available documents.
[More strict Swedish rules on radiation protection. New directives from the EU for health care].
Explore the source record for details and available documents.
Population structure and gene flow of the Atlantic walrus (Odobenus rosmarus rosmarus) in the eastern Atlantic Arctic based on mitochondrial DNA and microsatellite variation.
The population structure of the Atlantic walrus, Odobenus rosmarus rosmarus, was studied using 11 polymorphic microsatellites and restriction fragment length polymorphism detected in the NADH-dehydrogenase ND1, ND2 and ND3/4 segments in mtDNA. A total of 105 walrus samples were analysed from northwest (NW) Greenland, east (E) Greenland, Svalbard and Franz Joseph Land. Two of the 10 haplotypes detected in the four samples were diagnostic for the NW Greenland sample, which implied that the group of walruses in this area is evolutionary distinct from walruses in the other three areas. One individual sampled in E Greenland exhibited a Pacific haplotype, which proved a connection between the Pacific walrus and walruses in eastern Greenland. The Franz Joseph Land, Svalbard and E Greenland samples shared the most common haplotype, indicating very little differentiation at the mtDNA level. Gene flow (Nm) estimates among the four areas indicated a very restricted exchange of female genes between NW Greenland and the more eastern Atlantic Arctic samples, and a closer relationship between the three samples composing the eastern Atlantic Arctic. The genetic variation at 11 polymorphic microsatellite loci grouped individuals into three populations, NW Greenland, E Greenland and a common Franz Joseph Land-Svalbard population, which were connected by moderate gene flow.
Radiation-associated thyroid cancer--facts and fiction.
Thyroid cancer is a rare and complex disease and the thyroid contains various cell types from which specific diseases arise. The malignancies range from indolent to extremely aggressive. Several risk factors for thyroid cancers have been suggested, but only ionizing radiation has been found to have a causative effect. With the exception of tobacco, ionizing radiation is probably the most studied carcinogen there is. It is not yet possible to determine whether or not a specific cancer was induced by radiation and epidemiological studies therefore provide the primary data on cancer risk in man after exposure to ionizing radiation. The current epidemiological knowledge on radiation-associated thyroid cancer is reviewed, focusing on the sharply increased risks recently found among children in the Chernobyl area.
Sunbathing and sunbed use related to self-image in a randomized sample of Swedish adolescents.
In 1996 a randomized sample of 4,020 Swedish adolescents from three birth cohorts were sent a questionnaire consisting of 50 items concerning habitual sun-related behaviours and attitudes, knowledge about melanoma, risk perception and self-image. A total of 2,615 questionnaires were returned. Girls sunbathed and used sunbeds more than boys at all ages. Sunbathing and sunbed use increased with age. Boys who were most satisfied and girls least satisfied with themselves sunbathed most. Those who were least satisfied with themselves used sunbeds most frequently. Girls reported a higher perceived susceptibility to melanoma than did boys. The perception of susceptibility increased with age. Those who were least satisfied with themselves reported feeling most susceptible. The overall main reason for sunbathing was appearance, both for own sunbathing, and to an even higher degree, as a supposed reason for other adolescents' behaviour, and was reported most frequently by girls and the older age groups. The second most 'important' reason for sunbathing was 'feeling warm and comfortable'. Preventive programmes aimed at a change of sun related behaviours among Swedish adolescents have to be tailored to the climate and cultural conditions and must take into account that having a tan, and the warmth of the sun, are highly valued by most adolescents.
Outcome of reproduction in women irradiated for skin hemangioma in infancy.
The possible impact of early gonadal irradiation on the results of future pregnancies is unclear. This study is based on the progeny of 17,393 women who were treated with irradiation for skin hemangiomas at the age of 18 months or less. The mean ovarian dose was 6 cGy, and the maximum was 8.55 Gy. Using Swedish central health registers, the outcome of delivery was studied in these women; 19,494 infants born were identified. The treated women deviated from the general population by having a longer education and by smoking less. This may explain a reduced risk for low birth weight and preterm birth (not related to radiation dose). Women with ovarian doses greater than 1 cGy had fewer infants than women with a lower ovarian dose. An excess of perinatal deaths was evident as well as a slight excess in the rate of malformation, but neither was related to dose. There was a statistically significant trend of an increasing rate of neural tube defects with ovarian dose, possibly a chance result of multiple statistical testing. Cleft lip/palate occurred at levels significantly below expectation. No increase in the rate of infants with Down syndrome or in childhood malignancies was detected. No major adverse results in outcome of delivery were seen after ovarian irradiation in childhood with the possible exception of neural tube defects.
Intracranial tumors after exposure to ionizing radiation during infancy: a pooled analysis of two Swedish cohorts of 28,008 infants with skin hemangioma.
The risk of intracranial tumors after exposure to ionizing radiation during infancy has been studied in a pooled analysis of two Swedish hemangioma cohorts (n = 28,008). The mean absorbed intracranial dose was low (7 cGy, range 0-11.5 Gy). The cohorts were followed up in the Swedish Cancer Register for incident intracranial tumors during the period 1958-1993. Eighty-eight tumors were found in 86 individuals compared to 60.72 expected [standardized incidence ratio (SIR) 1.42, 95% confidence interval (CI) 1.13-1.75]. The SIR increased significantly in ascending dose categories (P = 0.02). Dose-response analyses were performed with Poisson regression methods. There was a significant effect of dose, and the dose-effect relationship was negatively modified by age at first treatment. This indicates a higher risk for those exposed earlier in life. A linear dose-response model modified by age at first treatment resulted in the best fit. The excess relative risk (ERR) was 2.7/Gy (95% CI 1.0-5.6). The ERR/Gy was 4.5 if the treatment was given before 5 months of age, 1.5 if it was given at 5-7 months and 0.4 if it was given later. The study thus strongly indicates that there exists a dose-response relationship between absorbed dose in the brain and the subsequent risk of developing an intracranial tumor and that the risk is higher among infants exposed at younger ages.
Omy0002DIAS: a highly polymorphic dinucleotide microsatellite in rainbow trout (Oncorhynchus mykiss).
Explore the source record for details and available documents.