Biomedical subjects

Peter von Rohr

Publications and source records attributed to Peter von Rohr.

6 recordsLinked to original sources

PubMed2006

From genetical genomics to systems genetics: potential applications in quantitative genomics and animal breeding.

This article reviews methods of integration of transcriptomics (and equally proteomics and metabolomics), genetics, and genomics in the form of systems genetics into existing genome analyses and their potential use in animal breeding and quantitative genomic modeling of complex traits. Genetical genomics or the expression quantitative trait loci (eQTL) mapping method and key findings in this research are reviewed. Various procedures and potential uses of eQTL mapping, global linkage clustering, and systems genetics are illustrated using actual analysis on recombinant inbred lines of mice with data on gene expression (for diabetes- and obesity-related genes), pathway, and single nucleotide polymorphism (SNP) linkage maps. Experimental and bioinformatics difficulties and possible solutions are discussed. The main uses of this systems genetics approach in quantitative genomics were shown to be in refinement of the identified QTL, candidate gene and SNP discovery, understanding gene-environment and gene-gene interactions, detection of candidate regulator genes/eQTL, discriminating multiple QTL/eQTL, and detection of pleiotropic QTL/eQTL, in addition to its use in reconstructing regulatory networks. The potential uses in animal breeding are direct selection on heritable gene expression measures, termed "expression assisted selection," and genetical genomic selection of both QTL and eQTL based on breeding values of the respective genes, termed "expression-assisted evaluation."

Animals↗

PubMed2005

Scoring functions for transcription factor binding site prediction.

BACKGROUND: Transcription factor binding site (TFBS) prediction is a difficult problem, which requires a good scoring function to discriminate between real binding sites and background noise. Many scoring functions have been proposed in the literature, but it is difficult to assess their relative performance, because they are implemented in different software tools using different search methods and different TFBS representations. RESULTS: Here we compare how several scoring functions perform on both real and semi-simulated data sets in a common test environment. We have also developed two new scoring functions and included them in the comparison. The data sets are from the yeast (S. cerevisiae) genome. Our new scoring function LLBG (least likely under the background model) performs best in this study. It achieves the best average rank for the correct motifs. Scoring functions based on positional bias performed quite poorly in this study. CONCLUSION: LLBG may provide an interesting alternative to current scoring functions for TFBS prediction.

Algorithms↗

PubMed2004

Sparse graphical Gaussian modeling of the isoprenoid gene network in Arabidopsis thaliana.

We present a novel graphical Gaussian modeling approach for reverse engineering of genetic regulatory networks with many genes and few observations. When applying our approach to infer a gene network for isoprenoid biosynthesis in Arabidopsis thaliana, we detect modules of closely connected genes and candidate genes for possible cross-talk between the isoprenoid pathways. Genes of downstream pathways also fit well into the network. We evaluate our approach in a simulation study and using the yeast galactose network.

Arabidopsis↗

PubMed2004

Limitations of codon adaptation index and other coding DNA-based features for prediction of protein expression in Saccharomyces cerevisiae.

The relationship between codon usage and protein/mRNA expression in S. cerevisiae has been extensively studied. Recently, protein expression data for the whole yeast genome was published. We investigate which properties of coding DNA sequences can be used to predict expression levels. The new algorithm by Carbone et al. for computing dominating codon bias in a genome is evaluated. It is concluded that it works at least as well as existing methods, and eliminates the need to arbitrarily choose a set of highly expressed genes. Also, the hypothesis that information on codon pair frequencies can be used to predict expression is investigated. Our conclusion is that codon pairs do not contribute more information than do single codon frequencies. Overall correlation between predicted and actual expression data using properties of coding DNA sequences is around 0.65. Hence, while being a useful source of information, the expression levels predicted by these methods should only be used as a rule of thumb.

Algorithms↗

PubMed2003

ATP-binding cassette transporter A1 locus is not a major determinant of HDL-C levels in a population at high risk for coronary heart disease.

ATP-binding cassette transporter A1 (ABCA1) transports cellular cholesterol to lipid-poor apolipoproteins. Mutations in the ABCA1 gene are linked to rare phenotypes, familial hypoalphalipoproteinemia (FHA) and Tangier disease (TD), characterized by markedly decreased plasma high-density lipoprotein cholesterol (HDL-C) levels. The aim was to test if the ABCA1 locus is a major locus regulating HDL-C levels in the homogenous Finnish population with a high prevalence of coronary heart disease (CHD). Firstly, the ABCA1 locus was tested for linkage to HDL-C levels in 35 families with premature CHD and low HDL-C levels. Secondly, 62 men with low HDL-C levels and CHD were screened for the five mutations known to cause FHA. Thirdly, polymorphisms of the ABCA1 gene were tested for an association with HDL-C levels in a population sample of 515 subjects. The ABCA1 locus was not linked to HDL-C levels in the CHD families, and no carriers of the FHA mutations were found. The AA596 genotype was associated with higher HDL-C levels compared with the GG and GA genotypes in the women, but not in the men. The G596A genotypes explained 4% and the A2589G genotypes 3% of the variation in plasma HDL-C levels in women. The data suggest that the ABCA1 locus is of minor importance in the regulation of HDL-C in Finns.

ATP Binding Cassette Transporter 1↗

PubMedDate not supplied

Bayesian QTL mapping using skewed Student-t distributions.

In most QTL mapping studies, phenotypes are assumed to follow normal distributions. Deviations from this assumption may lead to detection of false positive QTL. To improve the robustness of Bayesian QTL mapping methods, the normal distribution for residuals is replaced with a skewed Student-t distribution. The latter distribution is able to account for both heavy tails and skewness, and both components are each controlled by a single parameter. The Bayesian QTL mapping method using a skewed Student-t distribution is evaluated with simulated data sets under five different scenarios of residual error distributions and QTL effects.

Algorithms↗