Comparison of the accuracy of methods of computational haplotype inference using a large empirical dataset

BACKGROUND: Analyses of genetic data at the level of haplotypes provide increased accuracy and power to infer genotype-phenotype correlations and evolutionary history of a locus. However, empirical determination of haplotypes is expensive and laborious. Therefore, several methods of inferring haplotypes from unphased genotypic data have been proposed, but it is unclear how accurate each of the methods is or which methods are superior. The accuracy of some of the leading methods of computational haplotype inference (PL-EM, Phase, SNPHAP, Haplotyper) are compared using a large set of 308 empirically determined haplotypes based on 15 SNPs, among which 36 haplotypes were observed to occur. This study presents several advantages over many previous comparisons of haplotype inference methods: a large number of subjects are included, the number of known haplotypes is much smaller than the number of chromosomes surveyed, a range in values of linkage disequilibrium, presence of rare SNP alleles, and considerable dispersion in the frequencies of haplotypes. RESULTS: In contrast to some previous comparisons of haplotype inference methods, there was very little difference in the accuracy of the various methods in terms of either assignment of haplotypes to individuals or estimation of haplotype frequencies. Although none of the methods inferred all of the known haplotypes, the assignment of haplotypes to subjects was about 90% correct for individuals heterozygous for up to three SNPs and was about 80% correct for up to five heterozygous sites. All of the methods identified every haplotype with a frequency above 1%, and none assigned a frequency above 1% to an incorrect haplotype. CONCLUSIONS: All of the methods of haplotype inference have high accuracy and one can have confidence in inferences made by any one of the methods. The ability to identify even rare (≥ 1%) haplotypes is reassuring for efforts to identify haplotypes that contribute to disease in a significant proportion of a population. Assignment of haplotypes is relatively accurate among subjects heterozygous for up to 5 sites, and this might be the largest number of SNPs for which one should define haplotype blocks or have confidence in haplotype assignments

Mammalian mitochondrial DNA evolution: A comparison of the cytochrome b and cytochrome c oxidase II genes

The evolution of two mitochondrial genes, cytochrome b and cytochrome c oxidase subunit II, was examined in several eutherian mammal orders, with special emphasis on the orders Artiodactyla and Rodentia. When analyzed using both maximum parsimony, with either equal or unequal character weighting, and neighbor joining, neither gene performed with a high degree of consistency in terms of the phylogenetic hypotheses supported. The phylogenetic inconsistencies observed for both these genes may be the result of several factors including differences in the rate of nucleotide substitution among particular lineages (especially between orders), base composition bias, transition/transversion bias, differences in codon usage, and different constraints and levels of homoplasy associated with first, second, and third codon positions. We discuss the implications of these findings for the molecular systematics of mammals, especially as they relate to recent hypotheses concerning the polyphyly of the order Rodentia, relationships among the Artiodactyla, and various interordinal relationships.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48049/1/239_2004_Article_BF00163231.pd

Genome-wide analysis of the RpoN regulon in Geobacter sulfurreducens

Background The role of the RNA polymerase sigma factor RpoN in regulation of gene expression in Geobacter sulfurreducens was investigated to better understand transcriptional regulatory networks as part of an effort to develop regulatory modules for genome-scale in silico models, which can predict the physiological responses of Geobacter species during groundwater bioremediation or electricity production. Results An rpoN deletion mutant could not be obtained under all conditions tested. In order to investigate the regulon of the G. sulfurreducens RpoN, an RpoN over-expression strain was made in which an extra copy of the rpoN gene was under the control of a taclac promoter. Combining both the microarray transcriptome analysis and the computational prediction revealed that the G. sulfurreducens RpoN controls genes involved in a wide range of cellular functions. Most importantly, RpoN controls the expression of the dcuB gene encoding the fumarate/succinate exchanger, which is essential for cell growth with fumarate as the terminal electron acceptor in G. sulfurreducens. RpoN also controls genes, which encode enzymes for both pathways of ammonia assimilation that is predicted to be essential under all growth conditions in G. sulfurreducens. Other genes that were identified as part of the RpoN regulon using either the computational prediction or the microarray transcriptome analysis included genes involved in flagella biosynthesis, pili biosynthesis and genes involved in central metabolism enzymes and cytochromes involved in extracellular electron transfer to Fe(III), which are known to be important for growth in subsurface environment or electricity production in microbial fuel cells. The consensus sequence for the predicted RpoN-regulated promoter elements is TTGGCACGGTTTTTGCT. Conclusion The G. sulfurreducens RpoN is an essential sigma factor and a global regulator involved in a complex transcriptional network controlling a variety of cellular processes

Bioinformatic analysis of gene regulation in Geobacter sulfurreducens

Background Geobacteraceae are a family of microorganisms from the delta subdivision of Proteobacteria. They have potential for environmental bioremediation and electricity generation. In this presentation, we describe our recent bioinformatic analyses of gene regulation in Geobacter sulfurreducens, a model representative of this family. Results and conclusion We have developed an online database, GSEL (Geobacter Sequence Elements), which compiles regulatory information for G. sulfurreducens. We have recently completed the development of a new, significantly expanded and updated, relational version 2 of the GSEL database and its accompanying online query system, which compiles manually curated information on operon organization and transcription regulatory elements in the genome of G. sulfurreducens. GSEL v. 2 incorporates a graphical browser and provides significantly expanded search capabilities. It also includes new information on predicted and/or experimentally validated genome regulatory sites and provides links to information from microarray experiments stored in public gene expression databases, and to original publications describing how particular regulatory interactions were identified. Using sequence and gene expression analyses, we investigated target genes and promoters regulated by RpoN, an alternative RNA polymerase sigma factor, which regulates a variety of important cellular processes in G. sulfurreducens. Our current studies are focusing on an investigation of several transcription regulatory systems involved in RpoN-dependent regulatory pathways. We have investigated target regulatory sites for an enhancer binding protein, PilR, which participates in RpoN-dependent transcriptional regulation of the pilA gene encoding structural pilin. We predicted multiple PilR-regulated sites upstream of operons related to biosynthesis, assembly, and function of pili and flagella, type II secretory pathways, and cell wall biogenesis. We also investigated sequence changes and molecular classification of the TetR family of transcriptional regulators. In G. sulfurreducens, we identified RpoN-regulated promoters upstream of several operons containing tetR family genes. The genome of G. sulfurreducens contains nine tetR family genes. Some of them are located upstream of operons encoding functionally important c-type cytochromes. In order to better understand the roles of TetR family members in the ability of Geobacteraceae to participate in electron transfer, we investigated phylogenetic relationships among TetR proteins in Geobacteraceae and in other microbial species. We identified their conserved and variable domains, which may be important for the diversity of their functional roles, and classified them into subgroups based on sequence similarities

Orbiter Interface Unit and Early Communication System

This report describes the Orbiter Interface Unit (OIU) and the Early Communication System (ECOMM), which are systems of electronic hardware and software that serve as the primary communication links for the International Space Station (ISS). When a space shuttle is at or near the ISS during assembly and resupply missions, the OIU sends groundor crew-initiated commands from the space shuttle to the ISS and relays telemetry from the ISS to the space shuttle s payload data systems. The shuttle then forwards the telemetry to the ground. In the absence of a space shuttle, the ECOMM handles communications between the ISS and Johnson Space Center via the Tracking and Data Relay Satellite System (TDRSS). Innovative features described in the report include (1) a "smart data-buffering algorithm that helps to preserve synchronization (and thereby minimize loss) of telemetric data between the OIU and the space-shuttle payload data interleaver; (2) an ECOMM antenna-autotracking algorithm that selects whichever of two phased-array antennas gives the best TDRSS signal and electronically steers that antenna to track the TDRSS source; and (3) an ECOMM radiation-latchup controller, which detects an abrupt increase in current indicative of radiation-induced latchup and temporarily turns off power to clear the latchup, restoring power after the charge dissipates

An Empirical Comparison of Consumer Innovation Adoption Models: Implications for Subsistence Marketplaces

So called “pro-poor” innovations may improve consumer wellbeing in subsistence marketplaces. However, there is little research that integrates the area with the vast literature on innovation adoption. Using a questionnaire where respondents were asked to provide their evaluations about a mobile banking innovation, this research fills this gap by providing empirical evidence of the applicability of existing innovation adoption models in subsistence marketplaces. The study was conducted in Bangladesh among a geographically dispersed sample. The data collected allowed an empirical comparison of models in a subsistence context. The research reveals the most useful models in this context to be the Value Based Adoption Model and the Consumer Acceptance of Technology model. In light of these findings and further examination of the model comparison results the research also shows that consumers in subsistence marketplaces are not just motivated by functionality and economic needs. If organizations cannot enhance the hedonic attributes of a pro-poor innovation, and reduce the internal/external constraints related to adoption of that pro-poor innovation, then adoption intention by consumers will be lower