Frequency and distribution of rare electrophoretic mobility variants in a population of human newborns in Ann Arbor, Michigan

We have summarized the frequency and distribution of the rare variants encountered during the screening of 258 815 allele products, the products of 51 different loci, in 3242 predominantly Caucasian (88 %) newborns. Seventy-nine different rare variants, representing 187 occurrences, were identified. Almost 60 % (46 of 79) of the rare variants occurred as singletons while another 20 % were seen in two unrelated individuals. No rare variants were detected at 18 loci while no variants, either rare or polymorphic, were detected at 14 loci. More rare variants were identified at loci that were classified as polymorphic and also at loci where the gene products exist as a monomer. A positive relationship was observed between variant frequency, either classes or copies, and subunit molecular mass.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65173/1/j.1469-1809.1987.tb01065.x.pd

Studies of the purine analog associated modulation of human erythrocyte acid phosphatase activity

The activity of the human erythrocyte acid phosphatase is modulated by a series of structural analogs of purine. The unsubstituted purine base does not affect the enzyme activity. Addition of a substituent at the number six position usually generates an analog which activates the enzyme while similar substitutions at the two position usually generate an inhibitor. Pyrimidines are generally ineffective as modulators while several modifications of the imidazole ring of the purine analogs do not abolish the modulator activity of the purine analog. The level of response to all active analogs is isozyme specific. Differences in apparent relative affinities among the modulators are noted. The modulators with a positive effect on enzyme activity, are effective in the presence of methanol which is more effective than H 2 0 as a phosphate acceptor. These analogs act by enhancing the rate of transfer of phosphate to H 2 O, while decreasing the rate of transfer to methanol. The results suggest that the purine analogs may act by altering the rate of hydrolysis of the phosphoenzyme intermediate by H 2 0 or may change the rate-limiting step in the catalytic mechanism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45350/1/11010_2004_Article_BF00220780.pd

Characterization of a series of electrophoretic and enzyme activity variants of human glucose-phosphate isomerase

A total of 3438 cord blood samples were screened for variants of erythrocyte glucose-phosphate isomerase. The five different electrophoretic, three activity/deficiency, and one thermostability variants distributed among 27 unrelated Caucasian families of that population, plus two electrophoretic variants previously described from three Amerindian tribes were subsequently examined for cryptic variation using activity and thermostability criteria. Although thermostability differences were observed between electrophoretic variants, no microheterogeneity within any one class of variant was detected.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47616/1/439_2004_Article_BF00273834.pd

Exploration of methods to identify polymorphisms associated with variation in DNA repair capacity phenotypes

Elucidating the relationship between polymorphic sequences and risk of common disease is a challenge. For example, although it is clear that variation in DNA repair genes is associated with familial cancer, aging and neurological disease, progress toward identifying polymorphisms associated with elevated risk of sporadic disease has been slow. This is partly due to the complexity of the genetic variation, the existence of large numbers of mostly low frequency variants and the contribution of many genes to variation in susceptibility. There has been limited development of methods to find associations between genotypes having many polymorphisms and pathway function or health outcome. We have explored several statistical methods for identifying polymorphisms associated with variation in DNA repair phenotypes. The model system used was 80 cell lines that had been resequenced to identify variation; 191 single nucleotide substitution polymorphisms (SNPs) are included, of which 172 are in 31 base excision repair pathway genes, 19 in 5 anti-oxidation genes, and DNA repair phenotypes based on single strand breaks measured by the alkaline Comet assay. Univariate analyses were of limited value in identifying SNPs associated with phenotype variation. Of the multivariable model selection methods tested: the easiest that provided reduced error of prediction of phenotype was simple counting of the variant alleles predicted to encode proteins with reduced activity, which led to a genotype including 52 SNPs; the best and most parsimonious model was achieved using a two-step analysis without regard to potential functional relevance: first SNPs were ranked by importance determined by Random Forests Regression (RFR), followed by cross-validation in a second round of RFR modeling that included ever more SNPs in declining order of importance. With this approach 6 SNPs were found to minimize prediction error. The results should encourage research into utilization of multivariate analytical methods for epidemiological studies of the association of genetic variation in complex genotypes with risk of common diseases

Functional hemizygosity in the human genome: direct estimate from twelve erythrocyte enzyme loci

Cord blood samples from 2020 unrelated newborns were screened for levels of enzyme activity for twelve enzymes. The level of enzymatic activity for 100 determinations were consistent with the existence of an enzyme-deficiency allele. The frequency of deficiency alleles in the Black population (0.0071) was four times higher (after removal of the G6PD * A - variant) than in the Caucasian sample (0.0016). These frequencies are approximately double the frequency of rare electrophoretic mobility variants at similar loci in the same population. Given the number of functionally important loci in the human genome, these enzyme deficiency variants could constitute a significant health burden.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47620/1/439_2004_Article_BF00284477.pd

The development of study-specific self-efficacy during grammar school.(Zur Entwicklung der studienspezifischen Selbstwirksamkeit in der Oberstufe)

Article is in German. Even if more and more German adolescents acquire a university entrance qualification, not all of them finally enrol at a university. In particular, the transition from school to university strongly depends on parent’s education. Even with the same marks in school, adolescents from non-academic households are less likely to enrol in universities than adolescents from academic housholds. One important reason is their lower belief to master a university study. This study analyses a specific intervention in grammar school to improve study-specific self- efficacy, the belief in one’s capabilities to master a university study, using a longitudinal design. We apply a difference-in-difference framework and show that programme participation significantly improves the study-specific self-efficacy for puplis from non- academic families but not for those from academic families. Hence, such a programme could reduce social disparities between both groups

Effect of occupational exposure to cytostatics and nucleotide excision repair polymorphism on chromosomal aberrations frequency

Authors evaluated the incidence of total chromosomal aberrations (CA) and their types – chromatid-type (CTA) and chromosome-type (CSA) in peripheral blood lymphocytes from 72 oncologic unit's workers occupationally exposed to cytostatics in relationship to polymorphisms of DNA repair genes XPD, XPG and XPC. The cytogenetic analysis was used for determination of chromosomal aberrations frequency and PCR-RFLP method for polymorphisms of genes. Statistically higher frequency of total CA was detected in exposed group as compared to control (1.90±1.34% vs. 1.26±0.93%; Mann-Whitney U-test, p=0.001). There was not detected any difference between CTA and CSA (0.92±1.04% vs. 0.98±1.17%). Similarly, in genes XPD exon 23 and XPC exon 15 wasn't detected any difference neither in total chromosomal aberrations nor in CTA and CSA types. Statistically significant decrease of total chromosomal aberrations and CTA-type with presence of variant allele C was detected in gene XPG exon 15. Authors pointed out the importance of individual susceptibility factors in evaluation of effects of genotoxic agents, in that event, when the concentration does not meet the occupational exposure limit

Poaching and firm-sponsored training: first clean evidence

A series of seminal theoretical papers argues that poaching of employees may hamper company-sponsored general training. However, the extent of poaching, its determinants and consequences, remains an open empirical question. We provide a novel empirical identification strategy for poaching and investigate its causes and consequences. We find that only a small number of training firms in Germany are poaching victims. Firms are more likely to poach employees during an economic downturn. Training firms respond to poaching by lowering the share of new apprentice intakes in the following years