Common polymorphism in H19 associated with birthweight and cord blood IGF-II levels in humans.

BACKGROUND: Common genetic variation at genes that are imprinted and exclusively maternally expressed could explain the apparent maternal-specific inheritance of low birthweight reported in large family pedigrees. We identified ten single nucleotide polymorphisms (SNPs) in H19, and we genotyped three of these SNPs in families from the contemporary ALSPAC UK birth cohort (1,696 children, 822 mothers and 661 fathers) in order to explore associations with size at birth and cord blood IGF-II levels. RESULTS: Both offspring's and mother's H19 2992C>T SNP genotypes showed associations with offspring birthweight (P = 0.03 to P = 0.003) and mother's genotype was also associated with cord blood IGF-II levels (P = 0.0003 to P = 0.0001). The offspring genotype association with birthweight was independent of mother's genotype (P = 0.01 to P = 0.007). However, mother's untransmitted H19 2992T allele was also associated with larger birthweight (P = 0.04) and higher cord blood IGF-II levels (P = 0.002), suggesting a direct effect of mother's genotype on placental IGF-II expression and fetal growth. The association between mother's untransmitted allele and cord blood IGF-II levels was more apparent in offspring of first pregnancies than subsequent pregnancies (P-interaction = 0.03). Study of the independent Cambridge birth cohort with available DNA in mothers (N = 646) provided additional support for mother's H19 2992 genotype associations with birthweight (P = 0.04) and with mother's glucose levels (P = 0.01) in first pregnancies. CONCLUSION: The common H19 2992T allele, in the mother or offspring or both, may confer reduced fetal growth restraint, as indicated by associations with larger offspring birth size, higher cord blood IGF-II levels, and lower compensatory early postnatal catch-up weight gain, that are more evident among mother's smaller first-born infants.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Investigating the utility of combining Φ29 whole genome amplification and highly multiplexed single nucleotide polymorphism BeadArray™ genotyping

BACKGROUND: Sustainable DNA resources and reliable high-throughput genotyping methods are required for large-scale, long-term genetic association studies. In the genetic dissection of common disease it is now recognised that thousands of samples and hundreds of thousands of markers, mostly single nucleotide polymorphisms (SNPs), will have to be analysed. In order to achieve these aims, both an ability to boost quantities of archived DNA and to genotype at low costs are highly desirable. We have investigated Φ29 polymerase Multiple Displacement Amplification (MDA)-generated DNA product (MDA product), in combination with highly multiplexed BeadArray™ genotyping technology. As part of a large-scale BeadArray genotyping experiment we made a direct comparison of genotyping data generated from MDA product with that from genomic DNA (gDNA) templates. RESULTS: Eighty-six MDA product and the corresponding 86 gDNA samples were genotyped at 345 SNPs and a concordance rate of 98.8% was achieved. The BeadArray sample exclusion rate, blind to sample type, was 10.5% for MDA product compared to 5.8% for gDNA. CONCLUSIONS: We conclude that the BeadArray technology successfully produces high quality genotyping data from MDA product. The combination of these technologies improves the feasibility and efficiency of mapping common disease susceptibility genes despite limited stocks of gDNA samples

Evaluation and monitoring of terrestrial and aquatic insect biodiversity in forested and cleared watersheds at Camp Atterbury, Indiana.

Executive Summary Camp Atterbury is a 33,132 ha military installation near Edinburgh, Indiana. Construction of a 80 ha (4,550 ha with safety fan) Multi-Purpose Training Range (MPTR) began in 1998, and supports training for military vehicles and dismounted infantry, with a variety of stationary and moving targets. This study provides a baseline for long term monitoring and evaluation of natural communities to assess the impacts of construction of, and training in, the MPTR. We assessed both aquatic macroinvertebrate and terrestrial insect community diversity, abundance, and richness and similarity at a series of study plots using quantifiable, repeatable and replicated methods. These data provide baseline data facilitating long-term monitoring and assessment as a measure of ecosystem health, and allow evaluation of relationships between community composition and habitat metrics. Methods Eight terrestrial study sites, each comprised of a 30 m square plot, were randomly selected, with four of these placed in the cleared portions of the MPTR and four placed in adjacent upland forest. We used several sampling methods, with focus on three groups of taxa (all insect taxa, ants, and leafhoppers and kin) and compared the efficacy of both the methods and the groups as monitoring tools. Sampling methods included: 1) a Malaise trap (mesh tent-like device that captures flying insects) at each site; 2) four sweep sample transects at each site; 3) four leaf litter samples from each site, with invertebrates extracted using the Winkler method; and 4) Nine pitfall traps at each site. Samples were collect during Summer and Fall study periods, and this report gives results from the Summer sample period. Several habitat parameters were recorded, including a vegetation index, canopy cover, ground cover, and leaf litter depth. Dominant plant taxa were collected, and data loggers recorded soil and air temperature during the study. We sampled aquatic macroinvertebrates at three stream sites draining the MPTR. Invertebrates were collected in replicate samples with a dipnet and these were sorted and subsampled in the laboratory. Canopy cover and basic water chemistry data were collected, and data loggers recorded changes in terrestrial and aquatic temperature. An index of biotic integrity and taxon richness were used to evaluate the aquatic communities. Results and Discussion At least 409 taxa and 3776 specimens were collected at terrestrial sample sites during the Summer sampling period. In general, there were some differences among sites, among sampling methods, and among treatments (cleared MPTR versus forested) when we examined taxon richness and species diversity, but these differences could not always be fully resolved. While taxon richness and species diversity differed among treatments, and, in general, plots in the two treatments harbored different insect communities. Species accumulation curves and various estimators of taxon richness were used to evaluate the four sampling methods and the three groups of taxa (all taxa, ants, leafhoppers). Based on the performance of the different taxa (all, ants, leafhoppers) compared across the different methods (malaise sampling, Winkler extracted leaf litter samples, pitfall traps, and sweep samples), the single most effective taxon for monitoring was found to be the ants (Formicidae), and the single best method for monitoring was found to be pitfall trapping. We collected 818 specimens, primarily aquatic macroinvertebrates, from the three stream sites during Summer sampling. All three streams were dry during the fall sample period, and thus no aquatic macroinvertebrates were collected. Using Hilsenhoff’s (1988) family-level index of biotic integrity, water quality was classified as “good” at one site, and “fair” at the other two, although taxon richness was lowest at the site classified as good. In addition to invertebrates, numerous salamanders (Eurycea cirrigera, the Two-lined Salamander) were observed in the streams. 3 For aquatic invertebrates, we found that the small upstream portions that directly drained the MPTR only held water seasonally, and thus were not effective sites for monitoring of stream macroinvertebrates. There was insufficient separation between MPTR-influenced stream sites and control sites, and a lack of replication (few streams flowing away from the MPTR) precluded robust statistical analysis of the data we did obtain. The community of aquatic macroinvertebrates collected during this study appeared similar to the communities reported by Robinson (2004) elsewhere at Camp Atterbury in larger streams, and includes taxa typical of rocky bottom Midwestern forest streams. Fish were largely absent due to the intermittent nature of the streams. Salamanders were abundant in the streams, and because they are top predators in this seasonal habitat, they may be suitable subjects for studies of potential bioaccumulation of toxins. This study provides a snapshot of insect biodiversity at a point in time, thus providing baseline for any possible future monitoring of insect biodiversity. Sampling methods and analyses developed in this study could easily be implemented at a wide variety of other military installations to facilitate inventory and/or monitoring of insect biodiversity.Ope

Development of an integrated genome informatics, data management and workflow infrastructure: a toolbox for the study of complex disease genetics.

The genetic dissection of complex disease remains a significant challenge. Sample-tracking and the recording, processing and storage of high-throughput laboratory data with public domain data, require integration of databases, genome informatics and genetic analyses in an easily updated and scaleable format. To find genes involved in multifactorial diseases such as type 1 diabetes (T1D), chromosome regions are defined based on functional candidate gene content, linkage information from humans and animal model mapping information. For each region, genomic information is extracted from Ensembl, converted and loaded into ACeDB for manual gene annotation. Homology information is examined using ACeDB tools and the gene structure verified. Manually curated genes are extracted from ACeDB and read into the feature database, which holds relevant local genomic feature data and an audit trail of laboratory investigations. Public domain information, manually curated genes, polymorphisms, primers, linkage and association analyses, with links to our genotyping database, are shown in Gbrowse. This system scales to include genetic, statistical, quality control (QC) and biological data such as expression analyses of RNA or protein, all linked from a genomics integrative display. Our system is applicable to any genetic study of complex disease, of either large or small scale.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

In the dedicated pursuit of dedicated capital: restoring an indigenous investment ethic to British capitalism

Tony Blair’s landslide electoral victory on May 1 (New Labour Day?) presents the party in power with a rare, perhaps even unprecedented, opportunity to revitalise and modernise Britain’s ailing and antiquated manufacturing economy.* If it is to do so, it must remain true to its long-standing (indeed, historic) commitment to restore an indigenous investment ethic to British capitalism. In this paper we argue that this in turn requires that the party reject the very neo-liberal orthodoxies which it offered to the electorate as evidence of its competence, moderation and ‘modernisation’, which is has internalised, and which it apparently now views as circumscribing the parameters of the politically and economically possible

Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.METHODS AND RESULTS: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p&lt;1×10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p&lt;5×10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.CONCLUSIONS: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.</p

Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response

Author Correction: Environmental variability supports chimpanzee behavioural diversity

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21010-z