Dataset Information

Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysis.

ABSTRACT: In the past 15 years, the quantitative trait locus (QTL) mapping approach has been applied to crosses between different inbred mouse strains to identify genetic loci associated with plasma HDL cholesterol levels. Although successful, a disadvantage of this method is low mapping resolution, as often several hundred candidate genes fall within the confidence interval for each locus. Methods have been developed to narrow these loci by combining the data from the different crosses, but they rely on the accurate mapping of the QTL and the treatment of the data in a consistent manner. We collected 23 raw datasets used for the mapping of previously published HDL QTL and reanalyzed the data from each cross using a consistent method and the latest mouse genetic map. By utilizing this approach, we identified novel QTL and QTL that were mapped to the wrong part of chromosomes. Our new HDL QTL map allows for reliable combining of QTL data and candidate gene analysis, which we demonstrate by identifying Grin3a and Etv6, as candidate genes for QTL on chromosomes 4 and 6, respectively. In addition, we were able to narrow a QTL on Chr 19 to five candidates.

SUBMITTER: Ackert-Bicknell C

PROVIDER: S-EPMC3606003 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysis.

Ackert-Bicknell Cheryl C Paigen Beverly B Korstanje Ron R

Journal of lipid research 20130207 4

In the past 15 years, the quantitative trait locus (QTL) mapping approach has been applied to crosses between different inbred mouse strains to identify genetic loci associated with plasma HDL cholesterol levels. Although successful, a disadvantage of this method is low mapping resolution, as often several hundred candidate genes fall within the confidence interval for each locus. Methods have been developed to narrow these loci by combining the data from the different crosses, but they rely on ...[more]

PMID: 23393305

Similar Datasets

Project description:A rapid high-resolution genome-wide strategy for molecular mapping of major QTL(s)/gene(s) regulating important agronomic traits is vital for in-depth dissection of complex quantitative traits and genetic enhancement in chickpea. The present study for the first time employed a NGS-based whole-genome QTL-seq strategy to identify one major genomic region harbouring a robust 100-seed weight QTL using an intra-specific 221 chickpea mapping population (desi cv. ICC 7184 × desi cv. ICC 15061). The QTL-seq-derived major SW QTL (CaqSW1.1) was further validated by single-nucleotide polymorphism (SNP) and simple sequence repeat (SSR) marker-based traditional QTL mapping (47.6% R(2) at higher LOD >19). This reflects the reliability and efficacy of QTL-seq as a strategy for rapid genome-wide scanning and fine mapping of major trait regulatory QTLs in chickpea. The use of QTL-seq and classical QTL mapping in combination narrowed down the 1.37 Mb (comprising 177 genes) major SW QTL (CaqSW1.1) region into a 35 kb genomic interval on desi chickpea chromosome 1 containing six genes. One coding SNP (G/A)-carrying constitutive photomorphogenic9 (COP9) signalosome complex subunit 8 (CSN8) gene of these exhibited seed-specific expression, including pronounced differential up-/down-regulation in low and high seed weight mapping parents and homozygous individuals during seed development. The coding SNP mined in this potential seed weight-governing candidate CSN8 gene was found to be present exclusively in all cultivated species/genotypes, but not in any wild species/genotypes of primary, secondary and tertiary gene pools. This indicates the effect of strong artificial and/or natural selection pressure on target SW locus during chickpea domestication. The proposed QTL-seq-driven integrated genome-wide strategy has potential to delineate major candidate gene(s) harbouring a robust trait regulatory QTL rapidly with optimal use of resources. This will further assist us to extrapolate the molecular mechanism underlying complex quantitative traits at a genome-wide scale leading to fast-paced marker-assisted genetic improvement in diverse crop plants, including chickpea.

Project description:Gene-regulatory enhancers have been identified using various approaches, including evolutionary conservation, regulatory protein binding, chromatin modifications, and DNA sequence motifs. To integrate these different approaches, we developed EnhancerFinder, a two-step method for distinguishing developmental enhancers from the genomic background and then predicting their tissue specificity. EnhancerFinder uses a multiple kernel learning approach to integrate DNA sequence motifs, evolutionary patterns, and diverse functional genomics datasets from a variety of cell types. In contrast with prediction approaches that define enhancers based on histone marks or p300 sites from a single cell line, we trained EnhancerFinder on hundreds of experimentally verified human developmental enhancers from the VISTA Enhancer Browser. We comprehensively evaluated EnhancerFinder using cross validation and found that our integrative method improves the identification of enhancers over approaches that consider a single type of data, such as sequence motifs, evolutionary conservation, or the binding of enhancer-associated proteins. We find that VISTA enhancers active in embryonic heart are easier to identify than enhancers active in several other embryonic tissues, likely due to their uniquely high GC content. We applied EnhancerFinder to the entire human genome and predicted 84,301 developmental enhancers and their tissue specificity. These predictions provide specific functional annotations for large amounts of human non-coding DNA, and are significantly enriched near genes with annotated roles in their predicted tissues and lead SNPs from genome-wide association studies. We demonstrate the utility of EnhancerFinder predictions through in vivo validation of novel embryonic gene regulatory enhancers from three developmental transcription factor loci. Our genome-wide developmental enhancer predictions are freely available as a UCSC Genome Browser track, which we hope will enable researchers to further investigate questions in developmental biology.

Project description:The accuracy of motion prediction, utilized to overcome the system latency of motion management radiotherapy systems, is hampered by irregularities present in the patients' respiratory pattern. Audiovisual (AV) biofeedback has been shown to reduce respiratory irregularities. The aim of this study was to test the hypothesis that AV biofeedback improves the accuracy of motion prediction.An AV biofeedback system combined with real-time respiratory data acquisition and MR images were implemented in this project. One-dimensional respiratory data from (1) the abdominal wall (30 Hz) and (2) the thoracic diaphragm (5 Hz) were obtained from 15 healthy human subjects across 30 studies. The subjects were required to breathe with and without the guidance of AV biofeedback during each study. The obtained respiratory signals were then implemented in a kernel density estimation prediction algorithm. For each of the 30 studies, five different prediction times ranging from 50 to 1400 ms were tested (150 predictions performed). Prediction error was quantified as the root mean square error (RMSE); the RMSE was calculated from the difference between the real and predicted respiratory data. The statistical significance of the prediction results was determined by the Student's t-test.Prediction accuracy was considerably improved by the implementation of AV biofeedback. Of the 150 respiratory predictions performed, prediction accuracy was improved 69% (103/150) of the time for abdominal wall data, and 78% (117/150) of the time for diaphragm data. The average reduction in RMSE due to AV biofeedback over unguided respiration was 26% (p < 0.001) and 29% (p < 0.001) for abdominal wall and diaphragm respiratory motion, respectively.This study was the first to demonstrate that the reduction of respiratory irregularities due to the implementation of AV biofeedback improves prediction accuracy. This would result in increased efficiency of motion management techniques affected by system latencies used in radiotherapy.

Dataset Information

Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysis.

Publications

Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets