QTL global meta-analysis: are trait determining genes clustered?

Background: A key open question in biology is if genes are physically clustered with respect to their known functions or phenotypic effects. This is of particular interest for Quantitative Trait Loci (QTL) where a QTL region could contain a number of genes that contribute to the trait being measured. Results: We observed a significant increase in gene density within QTL regions compared to non-QTL regions and/or the entire bovine genome. By grouping QTL from the Bovine QTL Viewer database into 8 categories of non-redundant regions, we have been able to analyze gene density and gene function distribution, based on Gene Ontology (GO) with relation to their location within QTL regions, outside of QTL regions and across the entire bovine genome. We identified a number of GO terms that were significantly over represented within particular QTL categories. Furthermore, select GO terms expected to be associated with the QTL category based on common biological knowledge have also proved to be significantly over represented in QTL regions. Conclusion: Our analysis provides evidence of over represented GO terms in QTL regions. This increased GO term density indicates possible clustering of gene functions within QTL regions of the bovine genome. Genes with similar functions may be grouped in specific locales and could be contributing to QTL traits. Moreover, we have identified over-represented GO terminology that from a biological standpoint, makes sense with respect to QTL category type.Hanni Salih and David L Adelso

USDA Stakeholder Workshop on Animal Bioinformatics: Summary and Recommendations

An electronic workshop was conducted on 4 November–13 December 2002 to discuss current issues and needs in animal bioinformatics. The electronic (e-mail listserver) format was chosen to provide a relatively speedy process that is broad in scope, cost-efficient and easily accessible to all participants. Approximately 40 panelists with diverse species and discipline expertise communicated through the panel e-mail listserver. The panel included scientists from academia, industry and government, in the USA, Australia and the UK. A second ‘stakeholder’ e-mail listserver was used to obtain input from a broad audience with general interests in animal genomics. The objectives of the electronic workshop were: (a) to define priorities for animal genome database development; and (b) to recommend ways in which the USDA could provide leadership in the area of animal genome database development. E-mail messages from panelists and stakeholders are archived at http://genome.cvm.umn.edu/bioinfo/. Priorities defined for animal genome database development included: (a) data repository; (b) tools for genome analysis; (c) annotation; (d) practical application of genomic data; and (e) a biological framework for DNA sequence. A stable source of funding, such as the USDA Agricultural Research Service (ARS), was recommended to support maintenance of data repositories and data curation. Continued support for competitive grants programs within the USDA Cooperative State Research, Education and Extension Service (CSREES) was recommended for tool development and hypothesis-driven research projects in genome analysis. Additional stakeholder input will be required to continuously refine priorities and maximize the use of limited resources for animal bioinformatics within the USDA

The bovine QTL viewer: a web accessible database of bovine Quantitative Trait Loci

BACKGROUND: Many important agricultural traits such as weight gain, milk fat content and intramuscular fat (marbling) in cattle are quantitative traits. Most of the information on these traits has not previously been integrated into a genomic context. Without such integration application of these data to agricultural enterprises will remain slow and inefficient. Our goal was to populate a genomic database with data mined from the bovine quantitative trait literature and to make these data available in a genomic context to researchers via a user friendly query interface. DESCRIPTION: The QTL (Quantitative Trait Locus) data and related information for bovine QTL are gathered from published work and from existing databases. An integrated database schema was designed and the database (MySQL) populated with the gathered data. The bovine QTL Viewer was developed for the integration of QTL data available for cattle. The tool consists of an integrated database of bovine QTL and the QTL viewer to display QTL and their chromosomal position. CONCLUSION: We present a web accessible, integrated database of bovine (dairy and beef cattle) QTL for use by animal geneticists. The viewer and database are of general applicability to any livestock species for which there are public QTL data. The viewer can be accessed at

Genomic organization, annotation, and ligand-receptor inferences of chicken chemokines and chemokine receptor genes based on comparative genomics

BACKGROUND: Chemokines and their receptors play important roles in host defense, organogenesis, hematopoiesis, and neuronal communication. Forty-two chemokines and 19 cognate receptors have been found in the human genome. Prior to this report, only 11 chicken chemokines and 7 receptors had been reported. The objectives of this study were to systematically identify chicken chemokines and their cognate receptor genes in the chicken genome and to annotate these genes and ligand-receptor binding by a comparative genomics approach. RESULTS: Twenty-three chemokine and 14 chemokine receptor genes were identified in the chicken genome. All of the chicken chemokines contained a conserved CC, CXC, CX(3)C, or XC motif, whereas all the chemokine receptors had seven conserved transmembrane helices, four extracellular domains with a conserved cysteine, and a conserved DRYLAIV sequence in the second intracellular domain. The number of coding exons in these genes and the syntenies are highly conserved between human, mouse, and chicken although the amino acid sequence homologies are generally low between mammalian and chicken chemokines. Chicken genes were named with the systematic nomenclature used in humans and mice based on phylogeny, synteny, and sequence homology. CONCLUSION: The independent nomenclature of chicken chemokines and chemokine receptors suggests that the chicken may have ligand-receptor pairings similar to mammals. All identified chicken chemokines and their cognate receptors were identified in the chicken genome except CCR9, whose ligand was not identified in this study. The organization of these genes suggests that there were a substantial number of these genes present before divergence between aves and mammals and more gene duplications of CC, CXC, CCR, and CXCR subfamilies in mammals than in aves after the divergence

Infall, Outflow, Rotation, and Turbulent Motions of Dense Gas within NGC 1333 IRAS 4

Millimeter wavelength observations are presented of NGC 1333 IRAS 4, a group of highly-embedded young stellar objects in Perseus, that reveal motions of infall, outflow, rotation, and turbulence in the dense gas around its two brightest continuum objects, 4A and 4B. These data have finest angular resolution of approximately 2" (0.0034 pc) and finest velocity resolution of 0.13 km/s. Infall motions are seen from inverse P-Cygni profiles observed in H2CO 3_12-2_11 toward both objects, but also in CS 3-2 and N2H+ 1-0 toward 4A, providing the least ambiguous evidence for such motions toward low-mass protostellar objects. Outflow motions are probed by bright line wings of H2CO 3_12-2_11 and CS 3-2 observed at positions offset from 4A and 4B, likely tracing dense cavity walls. Rotational motions of dense gas are traced by a systematic variation of the N2H+ line velocities, and such variations are found around 4A but not around 4B. Turbulent motions appear reduced with scale, given N2H+ line widths around both 4A and 4B that are narrower by factors of 2 or 3 than those seen from single-dish observations. Minimum observed line widths of approximately 0.2 km/s provide a new low, upper bound to the velocity dispersion of the parent core to IRAS 4, and demonstrate that turbulence within regions of clustered star formation can be reduced significantly. A third continuum object in the region, 4B', shows no detectable line emission in any of the observed molecular species.Comment: LateX, 51 pages, 9 figures, accepted by Ap

Characterization of the equine 2\u27-5\u27 oligoadenylate synthetase 1 (OAS1) and ribonuclease L (RNASEL) innate immunity genes

BACKGROUND: The mammalian OAS/RNASEL pathway plays an important role in antiviral host defense. A premature stop-codon within the murine Oas1b gene results in the increased susceptibility of mice to a number of flaviviruses, including West Nile virus (WNV). Mutations in either the OAS1 or RNASEL genes may also modulate the outcome of WNV-induced disease or other viral infections in horses. Polymorphisms in the human OAS gene cluster have been previously utilized for case-control analysis of virus-induced disease in humans. No polymorphisms have yet been identified in either the equine OAS1 or RNASEL genes for use in similar case-control studies. RESULTS: Genomic sequence for equine OAS1 was obtained from a contig assembly generated from a shotgun subclone library of CHORI-241 BAC 100I10. Specific amplification of regions of the OAS1 gene from 13 horses of various breeds identified 33 single nucleotide polymorphisms (SNP) and two microsatellites. RNASEL cDNA sequences were determined for 8 mammals and utilized in a phylogenetic analysis. The chromosomal location of the RNASEL gene was assigned by FISH to ECA5p17-p16 using two selected CHORI-241 BAC clones. The horse genomic RNASEL sequence was assembled. Specific amplification of regions of the RNASEL gene from 13 horses identified 31 SNPs. CONCLUSION: In this report, two dinucleotide microsatellites and 64 single nucleotide polymorphisms within the equine OAS1 and RNASEL genes were identified. These polymorphisms are the first to be reported for these genes and will facilitate future case-control studies of horse susceptibility to infectious diseases

Characterization of the equine 2'-5' oligoadenylate synthetase 1 (OAS1) and ribonuclease L (RNASEL) innate immunity genes

Background The mammalian OAS/RNASEL pathway plays an important role in antiviral host defense. A premature stop-codon within the murine Oas1b gene results in the increased susceptibility of mice to a number of flaviviruses, including West Nile virus (WNV). Mutations in either the OAS1 or RNASEL genes may also modulate the outcome of WNV-induced disease or other viral infections in horses. Polymorphisms in the human OAS gene cluster have been previously utilized for case-control analysis of virus-induced disease in humans. No polymorphisms have yet been identified in either the equine OAS1 or RNASEL genes for use in similar case-control studies. Results Genomic sequence for equine OAS1 was obtained from a contig assembly generated from a shotgun subclone library of CHORI-241 BAC 100I10. Specific amplification of regions of the OAS1 gene from 13 horses of various breeds identified 33 single nucleotide polymorphisms (SNP) and two microsatellites. RNASEL cDNA sequences were determined for 8 mammals and utilized in a phylogenetic analysis. The chromosomal location of the RNASEL gene was assigned by FISH to ECA5p17-p16 using two selected CHORI-241 BAC clones. The horse genomic RNASEL sequence was assembled. Specific amplification of regions of the RNASEL gene from 13 horses identified 31 SNPs. Conclusion In this report, two dinucleotide microsatellites and 64 single nucleotide polymorphisms within the equine OAS1 and RNASEL genes were identified. These polymorphisms are the first to be reported for these genes and will facilitate future case-control studies of horse susceptibility to infectious diseases

A functional genomics catalogue of activated transcription factors during pathogenesis of pneumococcal disease

Background: Association analysis is an alternative to conventional family-based methods to detect the location of gene(s) or quantitative trait loci (QTL) and provides relatively high resolution in terms of defining the genome position of a gene or QTL. Seed protein and oil concentration are quantitative traits which are determined by the interaction among many genes with small to moderate genetic effects and their interaction with the environment. In this study, a genome-wide association study (GWAS) was performed to identify quantitative trait loci (QTL)controlling seed protein and oil concentration in 298 soybean germplasm accessions exhibiting a wide range of seed protein and oil content. Results: A total of 55,159 single nucleotide polymorphisms (SNPs) were genotyped using various methods including illumina Infinium and GoldenGate assays and 31,954 markers with minor allele frequency >0.10 were used to estimate linkage disequilibrium (LD) in heterochromatic and euchromatic regions. In euchromatic regions, the mean LD (r2) rapidly declined to 0.2 within 360 Kbp, whereas the mean LD declined to 0.2 at 9,600 Kbp in heterochromatic regions. The GWAS results identified 40 SNPs in 17 different genomic regions significantly associated with seed protein. Of these, the five SNPs with the highest associations and seven adjacent SNPs were located in the 27.6-30.0 Mbp region of Gm20. A major seed protein QTL has been previously mapped to the same location and potential candidate genes have recently been identified in this region. The GWAS results also detected 25 SNPs in 13 different genomic regions associated with seed oil. Of these markers, seven SNPs had a significant association with both protein and oil. Conclusions: This research indicated that GWAS not only identified most of the previously reported QTL controlling seed protein and oil, but also resulted in narrower genomic regions than the regions reported as containing these QTL. The narrower GWAS-defined genome regions will allow more precise marker-assisted allele selection and will expedite positional cloning of the causal gene(s)

Genome Stability Is in the Eye of the Beholder: CR1 Retrotransposon Activity Varies Significantly across Avian Diversity

Since the sequencing of the zebra finch genome it has become clear that avian genomes, while largely stable in terms of chromosome number and gene synteny, are more dynamic at an intrachromosomal level. A multitude of intrachromosomal rearrangements and significant variation in transposable element (TE) content have been noted across the avian tree. TEs are a source of genome plasticity, because their high similarity enables chromosomal rearrangements through nonallelic homologous recombination, and they have potential for exaptation as regulatory and coding sequences. Previous studies have investigated the activity of the dominant TE in birds, chicken repeat 1 (CR1) retrotransposons, either focusing on their expansion within single orders, or comparing passerines with nonpasserines. Here, we comprehensively investigate and compare the activity of CR1 expansion across orders of birds, finding levels of CR1 activity vary significantly both between and within orders. We describe high levels of TE expansion in genera which have speciated in the last 10 Myr including kiwis, geese, and Amazon parrots; low levels of TE expansion in songbirds across their diversification, and near inactivity of TEs in the cassowary and emu for millions of years. CR1s have remained active over long periods of time across most orders of neognaths, with activity at any one time dominated by one or two families of CR1s. Our findings of higher TE activity in species-rich clades and dominant families of TEs within lineages mirror past findings in mammals and indicate that genome evolution in amniotes relies on universal TE-driven processes

\u3cem\u3eOAS1\u3c/em\u3e Polymorphisms Are Associated with Susceptibility to West Nile Encephalitis in Horses

West Nile virus, first identified within the United States in 1999, has since spread across the continental states and infected birds, humans and domestic animals, resulting in numerous deaths. Previous studies in mice identified the Oas1b gene, a member of the OAS/RNASEL innate immune system, as a determining factor for resistance to West Nile virus (WNV) infection. A recent case-control association study described mutations of human OAS1 associated with clinical susceptibility to WNV infection. Similar studies in horses, a particularly susceptible species, have been lacking, in part, because of the difficulty in collecting populations sufficiently homogenous in their infection and disease states. The equine OAS gene cluster most closely resembles the human cluster, with single copies of OAS1, OAS3 and OAS2 in the same orientation. With naturally occurring susceptible and resistant sub-populations to lethal West Nile encephalitis, we undertook a case-control association study to investigate whether, similar to humans (OAS1) and mice (Oas1b), equine OAS1 plays a role in resistance to severe WNV infection. We identified naturally occurring single nucleotide mutations in equine (Equus caballus) OAS1 and RNASEL genes and, using Fisher\u27s Exact test, we provide evidence that mutations in equine OAS1 contribute to host susceptibility. Virtually all of the associated OAS1 polymorphisms were located within the interferon-inducible promoter, suggesting that differences in OAS1 gene expression may determine the host\u27s ability to resist clinical manifestations associated with WNV infection