Haplotype analysis of the low density lipoprotein receptor (LDLR) gene was performed in Norwegian subjects heterozygous for familial hypercholesterolemia (FH). Southern blot analysis of genomic DNA, using an exon 18 specific probe and the restriction enzyme NcoI, showed that two out of 57 unrelated FH subjects had an abnormal 3.6 kb band. Further analyses revealed that this abnormal band was due to a 9.6 kb deletion that included exons 16 and 17. The 5' deletion breakpoint was after 245 bp of intron 15, and the 3' deletion breakpoint was in exon 18 after nucleotide 3390 of cDNA. Thus, both the membrane-spanning and cytoplasmatic domains of the receptor had been deleted. A polymerase chain reaction (PCR) method was developed to identify this deletion among other Norwegian FH subjects. As a result of this screening one additional subject was found out of 124 subjects screened. Thus, three out of 181 (1.7%) unrelated Norwegian FH subject possessed this deletion. The deletion was found on the same haplotype in the three unrelated subjects, suggesting a common mutagenic event. The deletion is identical to a deletion (FH-Helsinki) that is very common among Finnish FH subjects. However, it is not yet known whether the mutations evolved separately in the two countries.
PURPOSE: There is very little data available on adaptation at adolescence after "visible adoptions" (children adopted from abroad), in terms of mental health, risk-taking and problem behaviour in comparison with nonadopted adolescents. This study describes such an outcome. MATERIAL AND METHOD: Data derived from self-reports from 125 adolescents aged 13-18 years who identified themselves as adopted, and who participated in two epidemiological surveys of 9329 adolescents. Their number was representative for children adopted from abroad. The other adolescents served as controls. RESULTS: Family life styles showed no differences between groups. Health was similar to that of the controls. Foreign adopted adolescents significantly often evaluated themselves as shorter and with early puberty. The proportion of adopted girls with suicidal thoughts was significantly larger, they also reported school truancy, not using safety belts, sexual intercourse, unpleasant sexual encounters, and contact with illicit drugs more often than the controls. The stress of early puberty could only partly explain this. CONCLUSIONS: Girls adopted from abroad, representing "visible adoptions", need additional attention and study during adolescence to expose causes for maladaption among some of them.
The antagonistic pleiotropy theory of senescence postulates genes or traits that have opposite effects on early-life and late-life performances. Because selection is generally weaker late in life, genes or traits that improve early-life performance but impair late-life performance should come to predominate. Variation in the strength of age-specific selection should then generate adaptive variation in senescence. We demonstrate this mechanism by comparing early and late breeders within a population of semelparous capital-breeding sockeye salmon (Oncorhynchus nerka). We show that early breeders (but not late breeders) are under strong selection for a long reproductive lifespan (RLS), which facilitates defence of their nests against disturbance by later females. Accordingly, early females invest less energy in egg production while reserving more for nest defence. Variation along this reproductive trade-off causes delayed or slower senescence in early females (average RLS of 26 days) than in late females (reproductive lifespan of 12 days). We use microsatellites to confirm that gene flow is sufficiently limited between early and late breeders to allow adaptive divergence in response to selection. Because reproductive trade-offs should be almost universal and selection acting on them should typically vary in time and space, the mechanism described herein may explain much of the natural variation in senescence.
Three groups of Aeromonas strains isolated from Finland lakes experiencing cyanobacterial blooms could not be assigned to any known species of this genus on the basis of 16S rRNA and rpoD gene sequences. The Multilocus Phylogenetic Analysis (MLPA) of the concatenated sequence of seven genes (gyrB, rpoD, recA, dnaJ, gyrA, dnaX and atpD; 4093bp) showed that the three groups of strains did not cluster with any known Aeromonas spp. and formed three independent lineages. This was confirmed by performing the analysis with their closest relatives using 15 genes (the latter 7 and cpn60, dnaK, gltA, mdh, radA, rpoB, tsf, zipA; 8751bp). Furthermore, ANI results between the genomes of the type strains of the three potential new species and those of their close relatives were all
METHOD: data using the Resident Assessment Instrument (RAI) from nursing home populations in five countries (Denmark, Iceland, Italy, Japan, USA) were assembled from 396277 residents. The distribution of a new quality of life measure, 'social engagement', embedded in the RAI and found to be reliable and valid in the USA, was examined and compared in the international samples. RESULTS: in all five countries' nursing home populations engagement was highest among residents with adequate functioning in activities of daily living (ADL) and cognition, but the level of social engagement differed considerably by country among residents with poor ADL functioning, who had adequate cognition. The lowest scores were in Italy and Japan. The amount of time residents spend in activities stratified by ADL and cognition reveal the same pattern cross-culturally--cognitively impaired residents are least actively involved. CONCLUSIONS: the Minimum Data Set measure of social engagement is stable across types of residents and across nations and can serve as a marker of nursing home quality.
The three-amino acid insertion/deletion (I/D) polymorphism in the apoB signal peptide (27 amino acid versus 24 amino acid signal peptide) was evaluated as a possible risk factor for myocardial infarction (MI) in a case-control study population comprising 238 MI survivors and 547 controls. In controls, homozygotes for the deletion allele (DD) had the highest mean levels of both total cholesterol and low density lipoprotein (LDL) cholesterol (LDLC), the homozygotes for the insertion allele (II) had the lowest mean values, while the heterozygotes (ID) had intermediate mean levels (p
Familial hypercholesterolaemia is an autosomal dominant disorder characterized by hypercholesterolaemia, xanthomas and premature coronary heart disease. Treatment of hypercholesterolemia is effective and consists of dietary changes and lipid lowering drugs. Only a minor proportion of familial hypercholesterolaemia patients are adequately treated, however. One explanation for this is assumed to be the relatively vague clinical diagnostic criteria applied. Because familial hypercholesterolaemia is caused by a mutation in the gene encoding the low density lipoprotein (LDL) receptor, mutation analysis of this gene could form the basis for specific diagnosis. 29 different mutations in the LDL receptor gene have been found to cause familial hypercholesterolaemia among Norwegian patients, and a total of 681 patients from 322 unrelated families have been provided with a molecular genetic diagnosis. We conclude that the use of molecular genetic analysis is feasible, and should be used clinically.
Data on parental consanguinity have been recorded for all births in Norway since 1967. Pregnancy outcome for offspring of 848 women mated to their first cousins were compared with offspring of 1,696 control women. The stillbirth rate was 23.6 per thousand for cases and 13.4 for controls. The neonatal death rate was 34.9 per thousand for cases and 14.3 for controls. The recurrence risk for sibs for early death was 9.4% for cases and 4.2% for controls. The mean offspring birth weight was significantly lower (3377 g vs. 3491 g), and the variance in birth weight was slightly larger for cases than controls. The percentage of children with malformations detected shortly after birth was 4.6% for cases and 2.2% for controls. The differences may be attributed to the increased homozygosity in offspring of first cousins. The results have relevance for genetic counselling to consanguineous couples, as well as for the understanding of the etiology of adverse pregnancy outcome and for elucidating the causes of variation in birth weight.
The increase in birth weight with parity was studied in sibships of 2, 3, and 4 children using large samples from the Norwegian Birth Registry. Families with full sibs were compared to families with maternal half-sibs. The sensitization hypothesis of Warburton and Naylor predicts no increase in birth weight with parity when the mother changes mate. The hypothesis was not supported by the data, since similar increases in birth weight with parity were found in both types of families. A small effect of the sex of the first child on the birth weight of the later born children was observed.
