UPDG: Utilities package for data analysis of Pooled DNA GWAS

<p>Abstract</p> <p>Background</p> <p>Despite being a well-established strategy for cost reduction in disease gene mapping, pooled DNA association study is much less popular than the individual DNA approach. This situation is especially true for pooled DNA genomewide association study (GWAS), for which very few computer resources have been developed for its data analysis. This motivates the development of UPDG (Utilities package for data analysis of Pooled DNA GWAS).</p> <p>Results</p> <p>UPDG represents a generalized framework for data analysis of pooled DNA GWAS with the integration of Unix/Linux shell operations, Perl programs and R scripts. With the input of raw intensity data from GWAS, UPDG performs the following tasks in a stepwise manner: raw data manipulation, correction for allelic preferential amplification, normalization, nested analysis of variance for genetic association testing, and summarization of analysis results. Detailed instructions, procedures and commands are provided in the comprehensive user manual describing the whole process from preliminary preparation of software installation to final outcome acquisition. An example dataset (input files and sample output files) is also included in the package so that users can easily familiarize themselves with the data file formats, working procedures and expected output. Therefore, UPDG is especially useful for users with some computer knowledge, but without a sophisticated programming background.</p> <p>Conclusions</p> <p>UPDG provides a free, simple and platform-independent one-stop service to scientists working on pooled DNA GWAS data analysis, but with less advanced programming knowledge. It is our vision and mission to reduce the hindrance for performing data analysis of pooled DNA GWAS through our contribution of UPDG. More importantly, we hope to promote the popularity of pooled DNA GWAS, which is a very useful research strategy.</p

Pathway analysis of complex diseases for GWAS, extending to consider rare variants, multi-omics and interactions

Version of RecordPublishe

Evaluation of proteoglycan gene polymorphisms as risk factors in the genetic susceptibility to high myopia

Author name used in this manuscript: Maurice K. H. Yap2011-2012 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

A DNA pooling-based case-control study of myopia candidate genes COL11A1, COL18A1, FBN1, and PLOD1 in a Chinese population

Author name used in this publication: Maurice K. H. Yap2010-2011 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Advanced AODV approach for efficient detection and mitigation of wormhole attack in MANET

Wireless Communication is an inevitable part of Smart Home domain. A Mobile Ad-Hoc Network (MANET) is defined as an arrangement of wireless mobile nodes which creates a temporary network for the communication. MANET suffers from both kinds of attacks, active and passive attacks at all the layers of the network model. The lacks of security measures of routing protocols allow attackers to intrude the network. Wormhole, the attack is generated by tunnels creation and it results in complete disruption of routing paths on MANET. The proposed security approach is to detect and mitigate wormhole attack. It is secured Ad hoc on demand distance vector (AODV) approach which efficiently finds wormhole attack present in a MANET and Digital signature is used to prevent it. This approach is based on a calculation of tunneling time taken by tunnel to analyze the behavior of wormhole. Afterward, it decides some static threshold value. Based upon this tunneling time and threshold value, it decides whether given node is wormhole node or trustworthy node. A digital signature and hash chain algorithm is applied to mitigate the wormhole node

Systematic investigation of the relationship between high myopia and polymorphisms of the MMP₂, TIMP₂, and TIMP₃ genes by a DNA pooling approach

Author name used in this manuscript: Maurice K. H. Yap2010-2011 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Role of cardiac mitofusins in cardiac conduction following simulated ischemia–reperfusion

Mitochondrial dysfunction induced by acute cardiac ischemia–reperfusion (IR), may increase susceptibility to arrhythmias by perturbing energetics, oxidative stress production and calcium homeostasis. Although changes in mitochondrial morphology are known to impact on mitochondrial function, their role in cardiac arrhythmogenesis is not known. To assess action potential duration (APD) in cardiomyocytes from the Mitofusins-1/2 (Mfn1/Mfn2)-double-knockout (Mfn-DKO) compared to wild-type (WT) mice, optical-electrophysiology was conducted. To measure conduction velocity (CV) in atrial and ventricular tissue from the Mfn-DKO and WT mice, at both baseline and following simulated acute IR, multi-electrode array (MEA) was employed. Intracellular localization of connexin-43 (Cx43) at baseline was evaluated by immunohistochemistry, while Cx-43 phosphorylation was assessed by Western-blotting. Mfn-DKO cardiomyocytes demonstrated an increased APD. At baseline, CV was significantly lower in the left ventricle of the Mfn-DKO mice. CV decreased with simulated-ischemia and returned to baseline levels during simulated-reperfusion in WT but not in atria of Mfn-DKO mice. Mfn-DKO hearts displayed increased Cx43 lateralization, although phosphorylation of Cx43 at Ser-368 did not differ. In summary, Mfn-DKO mice have increased APD and reduced CV at baseline and impaired alterations in CV following cardiac IR. These findings were associated with increased Cx43 lateralization, suggesting that the mitofusins may impact on post-MI cardiac-arrhythmogenesis

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies

Child, Maternal and Demographic Factors Influencing Caregiver-Reported Autistic Trait Symptomatology in Toddlers.

Current research on children's autistic traits in the general population relies predominantly on caregiver-report, yet the extent to which individual, caregiver or demographic characteristics are associated with informants' ratings has not been sufficiently explored. In this study, caregivers of 396 Singaporean two-year-olds from a birth cohort study completed the Quantitative Checklist for Autism in Toddlers. Children's gender, cognitive functioning and birth order, maternal age, and ethnic group membership were not significant predictors of caregiver-reported autistic traits. Poorer child language development and higher maternal depressive symptoms significantly predicted more social-communicative autistic traits, while lower maternal education predicted more behavioural autistic traits. Children's language and informants' educational level and depressive symptomatology may need to be considered in caregiver-reports of autistic traits.This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore—NMRC/TCR/004-NUS/2008 and NMRC/TCR/012-NUHS/2014. Additional funding was provided by the Ministry of Education AcRF Tier 1 funding grant R581000130112 awarded to the corresponding/senior author and Singapore Institute for Clinical Sciences—A*STAR