Genome Wide Association Mapping of Grain Arsenic, Copper, Molybdenum and Zinc in Rice (Oryza sativa L.) Grown at Four International Field Sites

The mineral concentrations in cereals are important for human health, especially for individuals who consume a cereal subsistence diet. A number of elements, such as zinc, are required within the diet, while some elements are toxic to humans, for example arsenic. In this study we carry out genome-wide association (GWA) mapping of grain concentrations of arsenic, copper, molybdenum and zinc in brown rice using an established rice diversity panel of,300 accessions and 36.9 k single nucleotide polymorphisms (SNPs). The study was performed across five environments: one field site in Bangladesh, one in China and two in the US, with one of the US sites repeated over two years. GWA mapping on the whole dataset and on separate subpopulations of rice revealed a large number of loci significantly associated with variation in grain arsenic, copper, molybdenum and zinc. Seventeen of these loci were detected in data obtained from grain cultivated in more than one field location, and six co-localise with previously identified quantitative trait loci. Additionally, a number of candidate genes for the uptake or transport of these elements were located near significantly associated SNPs (within 200 kb, the estimated global linkage disequilibrium previously employed in this rice panel). This analysis highlights a number of genomic regions and candidate genes for further analysis as well as the challenges faced when mapping environmentally-variable traits in a highly genetically structured diversity panel.

Cartographic veracity in medieval mapping: analyzing geographical variation in the Gough Map of Great Britain

This article explores statistical approaches for assessing the relative accuracy of medieval mapping. It focuses on one particular map, the Gough Map of Great Britain. This is an early and remarkable example of a medieval “national” map covering Plantagenet Britain. Conventionally dated to c. 1360, the map shows the position of places in and coastal outline of Great Britain to a considerable degree of spatial accuracy. In this article, aspects of the map's content are subjected to a systematic analysis to identify geographical variations in the map's veracity, or truthfulness. It thus contributes to debates among historical geographers and cartographic historians on the nature of medieval maps and mapping and, in particular, questions of their distortion of geographic space. Based on a newly developed digital version of the Gough Map, several regression-based approaches are used here to explore the degree and nature of spatial distortion in the Gough Map. This demonstrates that not only are there marked variations in the positional accuracy of places shown on the map between regions (i.e., England, Scotland, and Wales), but there are also fine-scale geographical variations in the spatial accuracy of the map within these regions. The article concludes by suggesting that the map was constructed using a range of sources, and that the Gough Map is a composite of multiscale representations of places in Great Britain. The article details a set of approaches that could be transferred to other contexts and add value to historic maps by enhancing understanding of their contents.

Anatomy and facies association of a drumlin in Co. Down, Northern Ireland, from seismic and electrical resistivity surveys

Seismic refraction and electrical resistivity geophysical techniques were used to reconstruct the internal architecture of a drumlin in Co. Down, Northern Ireland. Geophysical results were both validated and complemented by borehole drilling, ground water flow modelling, and geologic mapping. The geophysical anatomy of the drumlin consists of five successive layers with depth including; topsoil, partially saturated and saturated glacial tills, and weathered and more competent greywacke bedrock. There are numerous, often extensive inclusions of clay, sand, gravel, cobbles, and boulders within the topsoil and the till units. Together geophysical and geotechnical findings imply that the drumlin is part of the subglacial lodgement, melt-out, debris flow, sheet flow facies described by previous authors, and formed by re-sedimentation and streamlining of pre-existing sediments during deglaciation of the Late Devensian ice sheet. Seismic refraction imaging is particularly well suited to delineating layering within the drumlin, and is able to reconstruct depths to interfaces to within ± 0.5 m accuracy. Refraction imaging ascertained that the weathered bedrock layer is continuous and of substantial thickness, so that it acts as a basal aquifer which underdrains the bulk of the drumlin. Electrical resistivity imaging was found to be capable of delineating relative spatial changes in the moisture content of the till units, as well as mapping sedimentary inclusions within the till. The moisture content appeared to be elevated near the margins of the drumlin, which may infer a weakening of the drumlin slopes. Our findings advocate the use of seismic refraction and electrical resistivity methods in future sedimentological and geotechnical studies of internal drumlin architecture and drumlin formation, owing particularly to the superior, 3- D spatial coverage of these methods.

MEGF10 association with schizophrenia

Background: The 5q21-31 region has been implicated as harboring risk genes for schizophrenia in many linkage studies. In our previous report of stepwise fine mapping of this region, the MEGF10 gene was one of the genes showing consistent associations in our screening subsample. In this study, we carried out independent replication and expression studies of the MEGF10 gene.

Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis

We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P <5 × 10(-8)), increasing the number of known susceptibility loci to 25. The most associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further implicating JAK-STAT and cytokine signaling in disease pathogenesis. An additional five loci contained nonsynonymous variants in high linkage disequilibrium (LD; r(2) > 0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r(2) > 0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.

Genome-wide association study of Alzheimer's disease with psychotic symptoms

Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysis of three genome-wide association studies (GWASs) to identify loci that (1) increase susceptibility to an AD and subsequent psychotic symptoms; or (2) modify risk of psychotic symptoms in the presence of neurodegeneration caused by AD. In all, 1299 AD cases with psychosis (AD+P), 735 AD cases without psychosis (AD-P) and 5659 controls were drawn from Genetic and Environmental Risk in AD Consortium 1 (GERAD1), the National Institute on Aging Late-Onset Alzheimer's Disease (NIA-LOAD) family study and the University of Pittsburgh Alzheimer Disease Research Center (ADRC) GWASs. Unobserved genotypes were imputed to provide data on >1.8 million single-nucleotide polymorphisms (SNPs). Analyses in each data set were completed comparing (1) AD+P to AD-P cases, and (2) AD+P cases with controls (GERAD1, ADRC only). Aside from the apolipoprotein E (APOE) locus, the strongest evidence for association was observed in an intergenic region on chromosome 4 (rs753129; 'AD+PvAD-P' P=2.85 × 10(-7); 'AD+PvControls' P=1.11 × 10(-4)). SNPs upstream of SLC2A9 (rs6834555, P=3.0 × 10(-7)) and within VSNL1 (rs4038131, P=5.9 × 10(-7)) showed strongest evidence for association with AD+P when compared with controls. These findings warrant further investigation in larger, appropriately powered samples in which the presence of psychotic symptoms in AD has been well characterized.Molecular Psychiatry advance online publication, 18 October 2011; doi:10.1038/mp.2011.125.

Invariant Information Local Sub-map Filter (IILSF) for Efficient Simultaneous Localisation and Mapping of Large Environments

This paper presents an Invariant Information Local Sub-map Filter (IILSF) as a technique for consistent Simultaneous Localisation and Mapping (SLAM) in a large environment. It harnesses the benefits of sub-map technique to improve the consistency and efficiency of Extended Kalman Filter (EKF) based SLAM. The IILSF makes use of invariant information obtained from estimated locations of features in independent sub-maps, instead of incorporating every observation directly into the global map. Then the global map is updated at regular intervals. Applying this technique to the EKF based SLAM algorithm: (a) reduces the computational complexity of maintaining the global map estimates and (b) simplifies transformation complexities and data association ambiguities usually experienced in fusing sub-maps together. Simulation results show that the method was able to accurately fuse local map observations to generate an efficient and consistent global map, in addition to significantly reducing computational cost and data association ambiguities.

No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF)

The neuregulin-1 gene (NRG1) at chromosome 8p21-22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations. The shared ancestry between these populations led us to investigate the NRG1 polymorphisms and appropriate marker haplotypes for linkage and/or association to schizophrenia in the Irish study of high-density schizophrenia families (ISHDSF). Neither single-point nor multi-point linkage analysis of NRG1 markers gave evidence for linkage independent of our pre-existing findings telomeric on 8p. Analysis of linkage disequilibrium (LD) across the 252 kb interval encompassing the 7 marker core Icelandic/Scottish NRG1 haplotype revealed two separate regions of modest LD, comprising markers SNP8NRG255133, SNP8NRG249130 and SNP8NRG243177 (telomeric) and microsatellites 478B14-428, 420M9-1395, D8S1810 and 420M9-116I12 (centromeric). From single marker analysis by TRANSMIT and FBAT we found no evidence for association with schizophrenia for any marker. Haplotype analysis for the three SNPs in LD region 1 and, separately, the four microsatellites in LD region 2 (analyzed in overlapping 2-marker windows), showed no evidence for overtransmission of specific haplotypes to affected individuals. We therefore conclude that if NRG1 does contain susceptibility alleles for schizophrenia, they impact quite weakly on risk in the ISHDSF.

Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis

Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk there is significant heritability for host resistance to bovine TB (bTB) in dairy cattle. To identify resistance loci for bTB, we undertook a genome-wide association study in female Holstein-Friesian cattle with 592 cases and 559 age-matched controls from case herds. Cases and controls were categorised into distinct phenotypes: skin test and lesion positive vs skin test negative on multiple occasions, respectively these animals were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association using linear and logistic mixed models and regression (GRAMMAR), regional heritability mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that attained chromosome-wise significance, protein tyrosine phosphatase receptor T (PTPRT; P=4.8 × 10 -7) and myosin IIIB (MYO3B; P=5.4 × 10 -6). We estimated that 21% of the phenotypic variance in TB resistance could be explained by all of the informative single-nucleotide polymorphisms, of which the region encompassing the PTPRT gene accounted for 6.2% of the variance and a further 3.6% was associated with a putative copy number variant in MYO3B the results from this study add to our understanding of variation in host control of infection and suggest that genetic marker-based selection for resistance to bTB has the potential to make a significant contribution to bTB control.

Optimizing the efficiency of the sub-map technique for large-scale simultaneous localization and mapping

A technique for optimizing the efficiency of the sub-map method for large-scale simultaneous localization and mapping (SLAM) is proposed. It optimizes the benefits of the sub-map technique to improve the accuracy and consistency of an extended Kalman filter (EKF)-based SLAM. Error models were developed and engaged to investigate some of the outstanding issues in employing the sub-map technique in SLAM. Such issues include the size (distance) of an optimal sub-map, the acceptable error effect caused by the process noise covariance on the predictions and estimations made within a sub-map, when to terminate an existing sub-map and start a new one and the magnitude of the process noise covariance that could produce such an effect. Numerical results obtained from the study and an error-correcting process were engaged to optimize the accuracy and convergence of the Invariant Information Local Sub-map Filter previously proposed. Applying this technique to the EKF-based SLAM algorithm (a) reduces the computational burden of maintaining the global map estimates and (b) simplifies transformation complexities and data association ambiguities usually experienced in fusing sub-maps together. A Monte Carlo analysis of the system is presented as a means of demonstrating the consistency and efficacy of the proposed technique.

Compositional and Performance Mapping in Computer Chamber Music: A Case Study

The mapping problem is inherent to digital musical instruments (DMIs), which require, at the very least, an association between physical gestures and digital synthesis algorithms to transform human bodily performance into sound. This article considers the DMI mapping problem in the context of the creation and performance of a heterogeneous computer chamber music piece, a trio for violin, biosensors, and computer. Our discussion situates the DMI mapping problem within the broader set of interdependent musical interaction issues that surfaced during the composition and rehearsal of the trio. Through descriptions of the development of the piece, development of the hardware and software interfaces, lessons learned through rehearsal, and self-reporting by the participants, the rich musical possibilities and technical challenges of the integration of digital musical instruments into computer chamber music are demonstrated.