IBD sharing around the PPARG locus is not increased in dizygotic twins or their mothers.

Busjahn et al reported finding linkage between PPARG (3p25) and being a dizygotic (DZ) twin. We differentiate, as do the authors, between the conception of DZ twins, and being the viable result of such a conception.

Unique chemical parameters and microbial activity lead to increased archaeological preservation at the Roman frontier site of Vindolanda, UK.

Waterlogged burial conditions impact upon artefact preservation. One major determinant of preservation is presence and behaviour of microorganisms, however, unravelling the mechanisms, especially in waterlogged conditions is challenging. In this study, we analysed elemental composition, bacterial diversity and community structure from excavation trenches at the Roman Site of Vindolanda, Northumberland, UK, using pXRF and 16S rRNA gene amplicon sequencing. Excavation trenches provide information of different occupation periods. The results indicated that microbial communities were dominated by Firmicutes, Bacteroidetes and Proteobacteria at a phylum level. Samples which also had visible vivianite presence showed that there were marked increases in Methylophilus. Methylophilus might be associated with favourable preservation in these anaerobic conditions. More research is needed to clearly link the presence of Methylophilus with vivianite production. The study emphasises the need for further integration of chemical and microbiome approaches, especially in good preservation areas, to explore microbial and chemical degradation mechanisms.

Effect of the BDNF V166M polymorphism on working memory in healthy adolescents.

Brain-derived neurotrophic factor (BDNF) may play a role in modulating memory function and there is growing evidence that the BDNF V166M polymorphism may influence episodic memory in humans. However, previous association studies examining this polymorphism and working memory are inconsistent. The current study examined this association in a large sample of adolescent twin-pairs and siblings (785 individuals from 439 families). A range of measures (event-related potential, general performance and reaction time) was obtained from a delayed-response working-memory task and total association was examined using the quantitative transmission disequilibrium tests (QTDT) program. Analyses had approximately 93-97% power (alpha= 0.05) to detect an association accounting for as little as 2% of the variance in the phenotypes examined. Results indicated that the BDNF V166M polymorphism is not associated with variation in working memory in healthy adolescents.

The Genetical Response to Natural Selection by Varied Environments. IV. Gametic Disequilibrium in Spatially Varied Environments.

Gametic disequilibria between allozyme loci were related to spatial variation of the environment in caged populations of Drosophila melanogaster . Two experiments, one with flies collected at "Chateau Tahbilk," South Australia, and the other with flies from "Groningen," The Netherlands, were sampled at generations 16 and 32. Spatial variation of the environment was stimulated using three food media. Eight polymorphic allozyme loci were used to estimate gametic disequilibria from digenic combinations of allotypes. All populations were duplicated within an environment and maintained at about 2500 adults. Standardized gametic disequilibria were compared by a weighted least squares analysis of the z-transformed statistical correlation of allele frequencies. Gametic disequilibria were strongly dependent upon food niche and food-niche interactions. The effects also varied with sampling time and were similar in duplicate populations. Gametic disequilibria were most often detected in the "Groningen"-derived populations and their strength was not strongly associated with recombination fraction. Many of the disequilibria concerned unlinked loci. The strength of selection was probably considerable and populations were evolving genetic architectures which reflected niche selection by the different foods without marked genetic isolation between foods; gene frequencies did not vary between niches within a population cage.

Study of Alu sequences at the hypoxanthine phosphoribosyltransferase (hprt) encoding region of man.

The hypoxanthine phosphoribosyltransferase (hprt) encoding region of man is considered rich in Alu sequences: with 49 sequences present within 57 kilobases. Subfamily classification of the Alu sequences and identification of flanking direct repeats has been carried out to detect past rearrangements associated with their insertion into the region. Members of the Alu-J and three Alu-S subfamilies are present, along with the existence of free left arm sequences. Using available data, a comparison is made of the Alu subfamilies present at different gene regions. The heterogeneity in the number of each subfamily present at different genes shows that no one particular subfamily attained saturation in the genome. Several adjacent insertions of Alu sequences are seen at the hprt region. Furthermore two novel sequences are described, there is an incident where one Alu sequence has inserted into the middle poly(A) tract of an existing sequence at the hprt region; while another result from an Alu/Alu cross-over event elsewhere in the genome, before insertion into the hprt region. Once inserted, the Alu sequences are rarely subject to loss or rearrangement.

Oviposition in the period genotypes of Drosophila melanogaster.

Two behavioral rhythm phenotypes, oviposition and locomotor activity, have been compared in the four period genotypes (per+, pers, per0, and per1) of Drosophila. Period, signal-to-noise ratio, and phase were all analyzed and the genetic penetrance of the two characters was estimated. Significant rhythmicity of both oviposition and locomotor activity was evident in all four genotypes. The entrained and free-running periods of the activity rhythms of per+, pers, and per1 were within the range reported for these flies by previous workers, and rhythmic behavior was also shown by the per0 flies. The free-running period of the oviposition rhythm varied similarly between the four genotypes and showed significant correlation with that of the locomotor activity rhythm. It is suggested that both rhythm phenotypes are determined by the period gene, and estimates of the genetic penetrance of rhythmicity in oviposition and locomotor activity, based on period and signal-to-noise ratios (SNRs) of the different strains, are consistent with this hypothesis. The phase of maximum oviposition and locomotor activity showed greater variability between the genotypes and was not significantly correlated with period, suggesting that this rhythm characteristic is independent of mutations at the period locus.

An investigation of natural genetic variation in the circadian system of Drosophila melanogaster: rhythm characteristics and methods of quantification.

Variation in four characteristics of the circadian locomotor activity rhythm was investigated in 24 true-breeding strains of Drosophila melanogaster with a view to establishing methods of phenotypic measurement sufficiently robust to allow subsequent biometric analysis. Between them, these strains formed a representative sample of the genetic variability of a natural population. Period, phase, definition (the degree to which a rhythmic signal was obscured by noise), and rhythm waveform were all found to vary continuously among the strains, although within each strain the rhythm phenotype was remarkably consistent. Each characteristic was found to be sufficiently robust to permit objective measurement using several different methods of quantification, which were then compared.

Investigation of natural genetic variation in the circadian system of Drosophila melanogaster. II. Biometrical analyses of locomotor activity rhythms recorded in constant darkness.

The locomotor activity rhythms of 24 isochromosomal strains of Drosophila melanogaster were recorded in constant conditions, using an experimental design suitable for the serial screening with so many strains using limited equipment. The data obtained were subjected to biometrical genetic analysis. The results show that four characteristics of the rhythms (period, phase, definition, and waveform) display genetically based variation in expression and that each appears to be affected by a range of genes.

Genetic time-series analysis identifies a major QTL for in vivo alcohol metabolism not predicted by in vitro studies of structural protein polymorphism at the ADH1B or ADH1C loci.

After ingestion of a standardized dose of ethanol, alcohol concentrations were assessed, over 3.5 hours from blood (six readings) and breath (10 readings) in a sample of 412 MZ and DZ twins who took part in an Alcohol Challenge Twin Study (ACTS). Nearly all participants were subsequently genotyped on two polymorphic SNPs in the ADH1B and ADH1C loci known to affect in vitro ADH activity. In the DZ pairs, 14 microsatellite markers covering a 20.5 cM region on chromosome 4 that includes the ADH gene family were assessed, Variation in the timed series of autocorrelated blood and breath alcohol readings was studied using a bivariate simplex design. The contribution of a quantitative trait locus (QTL) or QTL's linked to the ADH region was estimated via a mixture of likelihoods weighted by identity-by-descent probabilities. The effects of allelic substitution at the ADH1B and ADH1C loci were estimated in the means part of the model simultaneously with the effects sex and age. There was a major contribution to variance in alcohol metabolism due to a QTL which accounted for about 64% of the additive genetic covariation common to both blood and breath alcohol readings at the first time point. No effects of the ADH1B*47His or ADH1C*349Ile alleles on in vivo metabolism were observed, although these have been shown to have major effects in vitro. This implies that there is a major determinant of variation for in vivo alcohol metabolism in the ADH region that is not accounted for by these polymorphisms. Earlier analyses of these data suggested that alcohol metabolism is related to drinking behavior and imply that this QTL may be protective against alcohol dependence.

A case of eye disease (Lippitudo) on the Roman frontier in Britain.

A newly excavated Roman report, written in ink on wood, on the strength of the First Cohort of Tungrians at Vindolanda in northern Britain, registers 31 men unfit, 15 as sick, 6 as wounded, the remainder, 10, with eye-disease, 'lippientes'. The paper also comments on the prevalence of eye-disease in antiquity and some of the suggested causes thereof.

Restriction endonuclease map variation and gene activity in the Adh region in a population of Drosophila melanogaster.

Variation within a 12 kb region containing the Adh gene was studied in 16 highly inbred lines of independent extraction from a population of Drosophila melanogaster, "Texas". Out of a selection of 8 hexanucleotide specific restriction endonucleases, four restriction site and five DNA insertion/deletion variations were observed and the heterozygosity per nucleotide was 0.004. Linkage disequilibrium between two restriction sites, considerably removed from and on either side of the Adh transcriptional unit, identified two major classes of chromosome or haplotype in the population. These two haplotypes were strongly associated with the capacity of lines to respond to the environment (genotype-environment interaction) in ADH activity. It was concluded that a control or regulatory polymorphism was present in the population in association with the Adh transcriptional unit.

The genetical response to natural selection by varied environments. II. Observations on replicate populations in spatially varied laboratory environments.

From each of two populations of Drosophila melanogaster, collected two months previously, from Chateau Tahbilk, S. Australia and Groningen, The Netherlands, duplicate populations were initiated in each of four environments which differed in their degree of environmental heterogeneity. Differing combinations of three food media based on oatmeal/treacle, potato or fig were used to simulate levels of environmental heterogeneity within the populations. The polymorphic loci, Adh, Est-6, G-6pdh, alpha-Gpdh, Pgm, Lap-D and Aph in both the Chateau Tahbilk and Groningen derived populations and 6Pgdh, which was only polymorphic in the populations which came from Chateau Tahbilk, were monitored in the experiment. The populations maintained a size of about 2500 adults and were sampled after 16 and 32 generations. Large changes of phenotype frequency were shown by all loci. Despite a frequent divergence of phenotype frequencies between duplicate cages, systematic effects of occasion and environment were present and allele frequencies at many loci were shown to be changing at a faster rate than could be due to random genetic drift. Genetic heterozygosity differed between environments but was not positively correlated with degree of environmental heterogeneity.

Genetical variation for enzyme activity in a population of Drosophila melanogaster. IV. Analysis of alcohol dehydrogenase activity in chromosome substitution lines.

Chromosome substitution lines derived from two inbred strains of Drosophila melanogaster homozygous for the AdhS allele of alcohol dehydrogenase but differing significantly in ADH activity have been analysed. Variation in activity can be attributed to all three major chromosomes. The effect of the second chromosome, where the ADH structural gene is located, can be modified significantly by the genotype of both the first and the third chromosomes. The most substantial single effect results from homozygous differences between the third chromosomes. In contrast, differences between the X chromosomes are revealed only when the second or second and third chromosomes are heterozygous.

Genetical variation for enzyme activity in a population of Drosophila melanogaster. II. Aspects of the inheritance of alcohol dehydrogenase activity in Adhs/s flies.

Two inbred lines of Drosophila melanogaster extracted from a laboratory cage population and homozygous for the AdhS allele of alcohol dehydrogenase (Adh) showed almost a twofold difference in specific activity. Analysis of generations derived from these lines showed that the genetic variation in ADH activity was controlled by additive gene action. There was no evidence of directional dominance or of non-allelic interactions. Although the Adh structural gene is on the second chromosome there was a significant effect of the X chromosome, indicating the action of modifying genes.

Genetical variation for enzyme activity in a population of Drosophila melanogaster. III. Dominance relationships for alcohol dehydrogenase activity.

Four inbred lines, two homozygous AdhS/S and two homozygous AdhF/F, were extracted from a laboratory cage population of Drosophila melanogaster and crossed in all combinations. Directional dominance for low ADH activity was present and confined to AdhF/S heterozygotes. The remaining genetical differences between the four lines for ADH activity were due to additive genetical variation. The frequency of the AdhS allele in the population was 0-89. The observed directional dominance for low ADH activity in AdhF/S heterozygotes corresponded to the general direction of selection for ADH activity within the population.

Genetical variation for enzyme activity in a population of Drosophila melanogaster. VII. Genotype-environment interaction for alcohol dehydrogenase (ADH) activity.

Genotype-environment interaction was detected for ADH activity amongst a set of 18 highly inbred lines of Drosophila melanogaster which had been extracted from the laboratory population, "Texas". The genotype-environment interaction for ADH activity was not wholly associated with genotype-environment interaction for body weight or total protein level. Detailed analyses of the responses of the individual inbred lines in ADH activity in relation to the environmental index, ej and following the procedure of Jinks and Pooni (1979), showed substantial diversity in the form of response. Lines homozygous for the AdhF allele were more environmentally sensitive than AdhS/S lines. Amongst the 16 AdhS/S lines, models of linear, quadratic or two intersecting-straight-lines were used to illustrate the varied responses of genotypes to the environment. The heterogeneity in the response characteristics of the inbred lines was attributed to variations in the conditions of culture media normally present within populations and laboratories. Moreover the non-linear responses shown by some lines to the environment are consistent with a model of genotype-environment interaction for ADH activity mediated by varied genotype-specific sensitivities to different environmental factors.

Genetical composition, temperature, density and selection in an enzyme polymorphism.

Selection in egg-to-adult viability was investigated at the Esterase-6 locus of Drosophila melanogaster. A factorial experiment was carried out with three variables, temperature, density and genetical composition; there were four temperatures (15 degrees, 20 degrees, 25 degrees and 30 degrees), three densities (115 ml, 10 ml and 2-5 ml of food). Strong frequency dependent selection was observed in many environments. The strength of the selection was very much modified by an interaction between temperature and density. The results are discussed in relation to evidence for a chemical mechanism which mediates frequency dependent selection, by conditioning, in the larval environment.

Restriction endonuclease map variation in the Adh region in populations of Drosophila melanogaster.

Variation within a 12-kb region of the second chromosome of Drosophila melanogaster which includes the Adh transcriptional unit was studied in 59 isochromosomal lines drawn from two populations. A number of restriction-fragment length polymorphisms due to both restriction-site presence/absence and insertions/deletions were revealed and the proportion of polymorphic nucleotides was estimated as 0.017 in population "Chateau Tahbilk" and 0.025 in population "Groningen." The presence within population Groningen of two complementary haplotypes at a high frequency was noted and its possible origin is discussed. The distribution of insertion/deletion variants within the populations was consistent with an associated deleterious effect and significant clustering of such variants to a 1-kb region approximately 4 kb from the transcriptional unit was also revealed. Analysis of gametic disequilibrium showed that its intensity was not related to the physical distance separating the markers on the chromosome and that strong disequilibria may flank weaker disequilibria. Two alternative interpretations of these data are advanced based upon natural selection and the hitchhiking effect of a favorable mutation. Comparisons of gametic disequilibrium among the four populations now surveyed at this locus were made using model fitting by weighted least squares and several significant contrasts were revealed.

Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei.

Histone H4 isoforms acetylated at lysines 5, 8, 12, or 16 have been shown, by indirect immunofluorescence with site-specific antisera, to have distinct patterns of distribution in interphase, polytene chromosomes from Drosophila larvae. H4 molecules acetylated at lysines 5 or 8 are distributed in overlapping, but nonidentical, islands throughout the euchromatic chromosome arms. beta-Heterochromatin in the chromocenter is depleted in these isoforms, but relatively enriched in H4 acetylated at lysine 12. H4 acetylated at lysine 16 is found at numerous sites along the transcriptionally hyperactive X chromosome in male larvae, but not in male autosomes or any chromosome in female cells. These findings support the hypothesis that H4 molecules acetylated at particular sites mediate unique and specific effects on chromatin function.

Molecular variation of the human elastin (ELN) gene in a normal human population.

DNA sequence diversity in the human elastin genomic region has been estimated by RFLP analysis in a normal human population. The proportion of polymorphic nucleotides and the degree of nucleotide diversity were 0.0034 and 0.0018 respectively. It is argued that the estimate of nucleotide diversity does not indicate strong purifying selection in the region. A total of 144 restriction sites were sampled in each of 80 independent chromosomes representing the screening of 58080 bp overall. Six main haplotypes were constructed; they represent at least 84% of the 80 chromosomes sampled. Analysis for linkage disequilibrium revealed two statistically significant comparisons out of 54 tests, approximately the proportion that would be statistically significant at the 5% level by chance. A higher order quadrigenic disequilibrium was detected. The relationship between the physical distance separating polymorphic restriction sites and linkage disequilibrium is discussed. The development of elastin haplotypes and knowledge of the pattern of linkage disequilibrium should aid the study of elastin related disease and human evolution.