Common PPARγ variants C161T and Pro12Ala are not associated with inflammatory bowel disease in an Australian cohort

Background & Aims: Peroxisome proliferator-activated receptor (PPAR) γ is a transcription factor, highly expressed in colonic epithelial cells, adipose tissue and macrophages, with an important role in the regulation of inflammatory pathways. The common PPARγ variants C161T and Pro12Ala have recently been associated with Ulcerative Colitis (UC) and an extensive UC phenotype respectively, in a Chinese population. PPARγ Pro12Ala variant homozygotes appear to be protected from the development of Crohn's disease (CD) in European Caucasians. Methods: A case-control study was performed for both variants (CD n=575, UC n=306, Controls n=360) using a polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis in an Australian IBD cohort. A transmission disequilibrium test was also performed using CD trios for the PPARγ C161T variant. Genotype-phenotype analyses were also undertaken. Results: There was no significant difference in genotype distribution data or allele frequency between CD and UC patients and controls. There was no difference in allele transmission for the C161T variant. No significant relationship between the variants and disease location was observed. Conclusions: We were unable to replicate in a Caucasian cohort the recent association between PPARγ C161T and UC or between PPARγ Pro12Ala and an extensive UC phenotype in a Chinese population. There are significant ethnic differences in genetic susceptibility to IBD and its phenotypic expression.

Five years of GWAS discovery

The past five years have seen many scientific and biological discoveries made through the experimental design of genome-wide association studies (GWASs). These studies were aimed at detecting variants at genomic loci that are associated with complex traits in the population and, in particular, at detecting associations between common single-nucleotide polymorphisms (SNPs) and common diseases such as heart disease, diabetes, auto-immune diseases, and psychiatric disorders. We start by giving a number of quotes from scientists and journalists about perceived problems with GWASs. We will then briefly give the history of GWASs and focus on the discoveries made through this experimental design, what those discoveries tell us and do not tell us about the genetics and biology of complex traits, and what immediate utility has come out of these studies. Rather than giving an exhaustive review of all reported findings for all diseases and other complex traits, we focus on the results for auto-immune diseases and metabolic diseases. We return to the perceived failure or disappointment about GWASs in the concluding section. © 2012 The American Society of Human Genetics.

Comparison of the performance of two commercial genome-wide association study genotyping platforms in Han Chinese samples

Most genome-wide association studies to date have been performed in populations of European descent, but there is increasing interest in expanding these studies to other populations. The performance of genotyping chips in Asian populations is not well established. Therefore, we sought to test the performance of widely used fixed-marker, genome-wide association studies chips in the Han Chinese population. Non-HapMap Chinese samples (n = 396) were genotyped using the Illumina OmniExpress and Affymetrix 6.0 platforms, whereas a subset also were genotyped using the Immunochip. Genotyped markers from the Affymetrix 6.0 and Illumina OmniExpress were used for full genome imputation based on the HapMap 2 JPT+CHB (Japanese from Tokyo, Japan and Chinese from Beijing, China) reference panel. The concordance between markers genotypes for the three platforms was very high whether directly genotyped or genotyped and imputed single nucleotide polymorphisms (SNPs; .99.8% for directly genotyped and .99.5% for genotyped and imputed SNPs, respectively) were compared. The OmniExpress chip data enabled more SNPs to be imputed, particularly SNPs with minor allele frequency .5%. The OmniExpress chip achieved better coverage of HapMap SNPs than the Affymetrix 6.0 chip (73.6% vs. 65.9%, respectively, for minor allele frequency .5%). The Affymetrix 6.0 and Illumina OmniExpress chip have similar genotyping accuracy and provide similar accuracy of imputed SNPs. The OmniExpress chip however provides better coverage of Asian HapMap SNPs, although its coverage of HapMap SNPs is moderate. © 2013 Jiang et al.

东亚人群 LMBR1 基因 Intron 5的遗传多样性研究

人LMBR1(Limb region 1 homolog (mouse)) 基因位于染色体7q36区域，全长约210.2 kb，含17个外显子，编码一个由490个氨基酸构成的跨膜蛋白。研究表明，LMBR1 基因的表达活性与脊椎动物四肢的手指或脚趾数目变化有关；另外，发生在其重要元件——intron 5 内的许多变异与多种表型的轴前多指症((PPD, Preaxial polydactyly)存在相关性，这主要是因为LMBR1 intron 5 内含有一个与骨骼系统发育有关的基因（SHH(Sonic hedgehog)基因）的远程顺式调控元件。本研究旨在探究LMBR1基因 intron 5 内的遗传多样性，进而评估HapMap计划的样本选择策略，并检测该区域是否受自然选择的作用。 国际人类基因组单体型图计划(HapMap Project，The International Haplotype Map Project) 于2002年10月正式启动，该计划旨在构建人类基因组中常见变异的遗传图式。自其数据发布以来，广泛应用于生物医学、群体遗传学等领域，在复杂疾病的遗传机理研究、自然选择的检测等方面做出了前所未有的贡献；但是HapMap计划中样本的代表性有待评估。 本研究中，我们综合考虑地理来源信息及线粒体单倍型类群 (Haplogroup)信息选择了41个东亚人作为样本（以保证样本的代表性），测定位于LMBR1 基因intron 5 内的目的片段中存在的单核苷酸多态性(SNP, Singe nucleotide polymorphism)位点，通过所得数据与HapMap数据的比较，发现二者之间差异显著且HapMap数据不能覆盖所有我们得到的常见变异，因而我们认为：HapMap计划中国部分的样本选择策略有待进一步完善。 关于自然选择的研究不仅可以使我们了解生物的进化机制，同时还对复杂疾病的遗传机理研究具有重要的提示作用，因而，对于自然选择的检测，一直以来都是生物学研究的重点。平衡选择是一种维持遗传多态性的自然选择方式，现已发现很多与特定疾病或性状相关的基因或调控序列受平衡选择的作用，如 G6PD 基因、PTC 基因、FMO3 基因、FSHB 基因及 CCR5 基因5’端顺式调控区等我们对41个东亚样本中LMBR1 intron 5 内一段长为9256 bp (Chr7: 156280954-156271699 (Build36))的序列进行以 Tajima’s D 检验为主的群体遗传学分析，发现该区域在进化历程中受到平衡选择的作用。LMBR1 intron 5 内的多态位点与多种表型的多指症存在相关性，受其调控的 SHH 基因在骨骼系统发育中具有重要作用，人类骨骼系统的适应性进化等三方面的因素为该区域受平衡选择的作用提供了进一步的佐证。 总之，本研究对HapMap计划的样本选择策略和数据应用提供了一定的参考；同时还发现一个与骨骼系统发育有关的基因调控元件受平衡选择的作用。

Minor allele frequency of myeloproliferative neoplasm mutations in the Irish blood donor population

Myeloproliferative neoplasms (MPNs) are rare diseases that include classic entities; polycythaemia vera, essential thrombocythaemia and primary myelofibrosis. In this short report, minor allele frequencies of common MPN mutations are compared between the Irish blood donor population and other populations of European descent using data from the Haplotype Map project. The Affymetrix array 6.0 platform was utilised identifying nine single nucleotide polymorphisms (SNPs) and six proxy SNPs. The variability of allele frequencies for MPN mutations could account for the different incidence rates seen between populations of European ancestry, giving a better understanding of the genetic predisposition to MPNs. 

Trans-Ancestral Studies Fine Map the SLE-Susceptibility Locus TNFSF4

We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: rs2205960-T (P = 1.71×10-34, OR = 1.43[1.26-1.60]) and rs1234317-T (P = 1.16×10-28, OR = 1.38[1.24-1.54]). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5′ region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5′ risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and lymphopenia. Our data confirm a global signal at TNFSF4 and a role for the expressed product at multiple stages of lymphocyte dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral mapping in a complex trait. © 2013 Manku et al.

Linkage disequilibrium and haplotype block structure in a composite beef cattle breed

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Combining ganglion cell topology and data of patients with glaucoma to determine a structure-function map

PURPOSE: To introduce techniques for deriving a map that relates visual field locations to optic nerve head (ONH) sectors and to use the techniques to derive a map relating Medmont perimetric data to data from the Heidelberg Retinal Tomograph. METHODS: Spearman correlation coefficients were calculated relating each visual field location (Medmont M700) to rim area and volume measures for 10 degrees ONH sectors (HRT III software) for 57 participants: 34 with glaucoma, 18 with suspected glaucoma, and 5 with ocular hypertension. Correlations were constrained to be anatomically plausible with a computational model of the axon growth of retinal ganglion cells (Algorithm GROW). GROW generated a map relating field locations to sectors of the ONH. The sector with the maximum statistically significant (P < 0.05) correlation coefficient within 40 degrees of the angle predicted by GROW for each location was computed. Before correlation, both functional and structural data were normalized by either normative data or the fellow eye in each participant. RESULTS: The model of axon growth produced a 24-2 map that is qualitatively similar to existing maps derived from empiric data. When GROW was used in conjunction with normative data, 31% of field locations exhibited a statistically significant relationship. This significance increased to 67% (z-test, z = 4.84; P < 0.001) when both field and rim area data were normalized with the fellow eye. CONCLUSIONS: A computational model of axon growth and normalizing data by the fellow eye can assist in constructing an anatomically plausible map connecting visual field data and sectoral ONH data.

Correlating eye gaze direction, depth and vehicle information on an interactive map for driver training

The over represented number of novice drivers involved in crashes is alarming. Driver training is one of the interventions aimed at mitigating the number of crashes that involve young drivers. Experienced drivers have better hazard perception ability compared to inexperienced drivers. Eye gaze patterns have been found to be an indicator of the driver's competency level. The aim of this paper is to develop an in-vehicle system which correlates information about the driver's gaze and vehicle dynamics, which is then used to assist driver trainers in assessing driving competency. This system allows visualization of the complete driving manoeuvre data on interactive maps. It uses an eye tracker and perspective projection algorithms to compute the depth of gaze and plots it on Google maps. This interactive map also features the trajectory of the vehicle and turn indicator usage. This system allows efficient and user friendly analysis of the driving task. It can be used by driver trainers and trainees to understand objectively the risks encountered during driving manoeuvres. This paper presents a prototype that plots the driver's eye gaze depth and direction on an interactive map along with the vehicle dynamics information. This prototype will be used in future to study the difference in gaze patterns in novice and experienced drivers prior to a certain manoeuvre.

The Brisbane media map : participatory design and authentic learning to link students and industry

The Brisbane Media Map is both an online resource and a tertiary-level authentic learning project. The Brisbane Media Map is an online database which provides a detailed overview of about 600 media industry organisations in Brisbane, Australia. In addition to providing contact details and synopses for each organisation’s profile, the Brisbane Media Map also includes supplementary information on current issues, trends, and individuals in the media and communication industry sectors. This resource is produced and updated annually by final-year undergraduate Media and Communication students. This article introduces the Brisbane Media Map, its functionality and systems design approach, as well as its alignment with key learning infrastructures. It examines authentic learning as the pedagogical framework underpinning the ongoing development work of the resource and highlights some synergies of this framework with participatory design principles. The Brisbane Media Map is a useful example of an authentic learning approach that successfully engages students of non-traditional and non-design areas of study in human-computer interaction, usability, and participatory design activities.

A distributed knowledge management infrastructure based on a Topic Map grid

Modern enterprise knowledge management systems typically require distributed approaches and the integration of numerous heterogeneous sources of information. A powerful foundation for these tasks can be Topic Maps, which not only provide a semantic net-like knowledge representation means and the possibility to use ontologies for modelling knowledge structures, but also offer concepts to link these knowledge structures with unstructured data stored in files, external documents etc. In this paper, we present the architecture and prototypical implementation of a Topic Map application infrastructure, the ‘Topic Grid’, which enables transparent, node-spanning access to different Topic Maps distributed in a network.

Enhancing digital road map with lane details extracted from large-scale stereo aerial imagery using object-oriented image analysis

Precise, up-to-date and increasingly detailed road maps are crucial for various advanced road applications, such as lane-level vehicle navigation, and advanced driver assistant systems. With the very high resolution (VHR) imagery from digital airborne sources, it will greatly facilitate the data acquisition, data collection and updates if the road details can be automatically extracted from the aerial images. In this paper, we proposed an effective approach to detect road lane information from aerial images with employment of the object-oriented image analysis method. Our proposed algorithm starts with constructing the DSM and true orthophotos from the stereo images. The road lane details are detected using an object-oriented rule based image classification approach. Due to the affection of other objects with similar spectral and geometrical attributes, the extracted road lanes are filtered with the road surface obtained by a progressive two-class decision classifier. The generated road network is evaluated using the datasets provided by Queensland department of Main Roads. The evaluation shows completeness values that range between 76% and 98% and correctness values that range between 82% and 97%.