Gene-level quantitative trait mapping in Caenorhabditis elegans.
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ABSTRACT:
SUBMITTER: Noble LM
PROVIDER: S-EPMC8022935 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Positional cloning of mutations in model genetic systems is a powerful method for the identification of targets of medical and agricultural importance. To facilitate the high-throughput mapping of mutations in Caenorhabditis elegans, we have identified a further 9602 putative new single nucleotide polymorphisms (SNPs) between two C. elegans strains, Bristol N2 and the Hawaiian mapping strain CB4856, by sequencing inserts from a CB4856 genomic DNA library and using an informatics pipeline to compare sequences with the canonical N2 genomic sequence. When combined with data from other laboratories, our marker set of 17,189 SNPs provides even coverage of the complete worm genome. To date, we have confirmed >1099 evenly spaced SNPs (one every 91 +/- 56 kb) across the six chromosomes and validated the utility of our SNP marker set and new fluorescence polarization-based genotyping methods for systematic and high-throughput identification of genes in C. elegans by cloning several proprietary genes. We illustrate our approach by recombination mapping and confirmation of the mutation in the cloned gene, dpy-18.
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Project description:Time to flowering and maturity in soybean is controlled by loci E1 to E5, and E7 to E9. These loci were assigned to molecular linkage groups (MLGs) except for E5. This study was conducted to map the E5 locus using F2 populations expected to segregate for E5. F2 populations were subjected to quantitative trait locus (QTL) analysis for days to flowering (DF) and maturity (DM). In Harosoy-E5 × Clark-e2 population, QTLs for DF and DM were found at a similar position with E2. In Harosoy × Clark-e2E5 population, QTLs for DF and DM were found in MLG D1a and B1, respectively. In Harosoy-E5Dt2 × Clark-e2 population, a QTL for DF was found in MLG B1. Thus, results from these populations were not fully consistent, and no candidate QTL for E5 was found. In Harosoy × PI 80837 population, from which E5 was originally identified, QTLs corresponding to E1 and E3 were found, but none for E5 existed. Harosoy and PI 80837 had the e2-ns allele whereas Harosoy-E5 had the E2-dl allele. The E2-dl allele of Harosoy-E5 may have been generated by outcrossing and may be responsible for the lateness of Harosoy-E5. We conclude that a unique E5 gene may not exist.
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Project description:Mutations in mitochondrial genome have epistatic effects on organisms depending on the nuclear background, but a role for the compatibility of mitochondrial-nuclear genomes (mit-n) in the quantitative nature of a complex trait remains unexplored. We studied a panel of recombinant inbred advanced intercrossed lines (RIAILs) of C. elegans that were established from a cross between the N2 and HW strains. We determined the HW nuclear genome content and the mitochondrial type (HW or N2) of each RIAIL strain. We found that the degree of mit-n compatibility was correlated with the lifespans but not the foraging behaviors of RIAILs. Several known aging-associated QTLs individually showed no relationship with mitotypes but collectively a weak trend consistent with a role in mit-n compatibility. By association mapping, we identified 293 SNPs that showed linkage with lifespan and a relationship with mitotypes consistent with a role in mit-n compatibility. We further found an association between mit-n compatibility and several functional characteristics of mitochondria as well as the expressions of genes involved in the respiratory oxidation pathway. The results provide the first evidence implicating mit-n compatibility in the quantitative nature of a complex trait, and may be informative to certain evolutionary puzzles on hybrids.
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Project description:Most heritable behavioral traits have a complex genetic basis, but few multigenic traits are understood at a molecular level. Here we show that the C. elegans strains N2 and CB4856 have opposite behavioral responses to simultaneous changes in environmental O(2) and CO(2). We identify two quantitative trait loci (QTL) that affect this trait and map each QTL to a single-gene polymorphism. One gene, npr-1, encodes a previously described neuropeptide receptor whose high activity in N2 promotes CO(2) avoidance. The second gene, glb-5, encodes a neuronal globin domain protein whose high activity in CB4856 modifies behavioral responses to O(2) and combined O(2)/CO(2) stimuli. glb-5 acts in O(2)-sensing neurons to increase O(2)-evoked calcium signals, implicating globins in sensory signaling. An analysis of wild C. elegans strains indicates that the N2 alleles of npr-1 and glb-5 arose recently in the same strain background, possibly as an adaptation to laboratory conditions.
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Project description:The gene (odc-1) encoding ornithine decarboxylase, a key enzyme in polyamine biosynthesis, was cloned and characterized. Two introns interrupt the coding sequence of the gene. The deduced protein contains 422 amino acids and is homologous to ornithine decarboxylases of other eukaryotic species. In vitro translation of a transcript of the cDNA yielded an enzymatically active product. The mRNA is 1.5 kb in size and is formed by trans-splicing to SL1, a common 5' RNA segment. odc-1 maps to the middle of LG V, between dpy-11 and unc-42 and near a breakpoint of the nDf32 deficiency strain. Enzymatic activity is low in starved stage 1 (L1) larva and, after feeding, rises progressively as the worms develop. Targeted gene disruption was used to create a null allele. Homozygous mutants are normally viable and show no apparent defects, with the exception of a somewhat reduced brood size. In vitro assays for ornithine decarboxylase activity, however, show no detectable enzymatic activity, suggesting that ornithine decarboxylase is dispensible for nematode growth in the laboratory.
| S-EPMC1206631 | biostudies-other
Project description:Coordinated regulation of gene expression levels across a series of experimental conditions provides valuable information about the functions of correlated transcripts. The consideration of gene expression correlation over a time or tissue dimension has proved valuable in predicting gene function. Here, we consider correlations over a genetic dimension. In addition to identifying coregulated genes, the genetic dimension also supplies us with information about the genomic locations of putative regulatory loci. We calculated correlations among approximately 45,000 expression traits derived from 60 individuals in an F2 sample segregating for obesity and diabetes. By combining the correlation results with linkage mapping information, we were able to identify regulatory networks, make functional predictions for uncharacterized genes, and characterize novel members of known pathways. We found evidence of coordinate regulation of 174 G protein-coupled receptor protein signaling pathway expression traits. Of the 174 traits, 50 had their major LOD peak within 10 cM of a locus on Chromosome 2, and 81 others had a secondary peak in this region. We also characterized a Riken cDNA clone that showed strong correlation with stearoyl-CoA desaturase 1 expression. Experimental validation confirmed that this clone is involved in the regulation of lipid metabolism. We conclude that trait correlation combined with linkage mapping can reveal regulatory networks that would otherwise be missed if we studied only mRNA traits with statistically significant linkages in this small cross. The combined analysis is more sensitive compared with linkage mapping alone.
| S-EPMC1331977 | biostudies-literature
Project description:Coordinated regulation of gene expression levels across a series of experimental conditions provides valuable information about the functions of correlated transcripts. To map gene regulatory pathways, we used microarray-derived gene expression measurements in 60 individuals of an F2 sample segregating for diabetes. We performed correlation analysis among ~40,000 expression traits. By combining correlation among expression traits and linkage mapping information, we were able to identify regulatory networks, make functional predictions to uncharacterized genes, and characterize novel members of known pathways. Using 36 seed traits, we found evidence of coordinate regulation of 160 G-protein coupled receptor (GPCR) pathway expression traits. Of the 160 traits, 50 had their major LOD peak within 8 cM of a locus on chromosome 2, and 81 others had a secondary peak in this region. A previously uncharacterized Riken cDNA clone, which showed strong correlation with stearoyl CoA desaturase 1 expression, was experimentally validated to be responsive to conditions that regulate lipid metabolism. Using linkage mapping, we identified multiple genes whose expression is under the control of transcription regulatory loci. Trait-correlation combined with linkage mapping can reveal regulatory networks that would otherwise be missed if we only studied mRNA traits with statistically significant linkages in this small cross. The combined analysis is more sensitive compared with linkage mapping only. References: Kendziorski C., M. Chen, M. Yuan, H. Lan, and A.D. Attie. Statistical Methods for Expression Quantitative Trait Loci (eQTL) Mapping. Biometrics, to appear, 2005. Lan H, Chen M, Flowers JB, Yandell BS, Stapleton DS, et al. (2006) Combined Expression Trait Correlations and Expression Quantitative Trait Locus Mapping. PLoS Genet 2(1): e6. Keywords: Genetics of gene expression
2005-09-21 | GSE3330 | GEO
Project description:We present an approach for quantitative trait locus (QTL) mapping, termed as 'lineage-specific QTL mapping', for inferring allelic changes of QTL evolution along with branches in a phylogeny. We describe and analyze the simplest case: by adding a third taxon into the normal procedure of QTL mapping between pairs of taxa, such inferences can be made along lineages to a presumed common ancestor. Although comparisons of QTL maps among species can identify homology of QTLs by apparent co-location, lineage-specific mapping of QTL can classify homology into (1) orthology (shared origin of QTL) versus (2) paralogy (independent origin of QTL within resolution of map distance). In this light, we present a graphical method that identifies six modes of QTL evolution in a three taxon comparison. We then apply our model to map lineage-specific QTLs for inbreeding among three taxa of yellow monkey-flower: Mimulus guttatus and two inbreeders M. platycalyx and M. micranthus, but critically assuming outcrossing was the ancestral state. The two most common modes of homology across traits were orthologous (shared ancestry of mutation for QTL alleles). The outbreeder M. guttatus had the fewest lineage-specific QTL, in accordance with the presumed ancestry of outbreeding. Extensions of lineage-specific QTL mapping to other types of data and crosses, and to inference of ancestral QTL state, are discussed.
| S-EPMC3716265 | biostudies-literature
Project description:Mendelian loci that control the expression levels of transcripts are called expression quantitative trait loci (eQTL). When mapping eQTL, we often deal with thousands of expression traits simultaneously, which complicates the statistical model and data analysis. Two simple approaches may be taken in eQTL analysis: (1) individual transcript analysis in which a single expression trait is mapped at a time and the entire eQTL mapping involves separate analysis of thousands of traits and (2) individual marker analysis where differentially expressed transcripts are detected on the basis of their association with the segregation pattern of an individual marker and the entire analysis requires scanning markers of the entire genome. Neither approach is optimal because data are not analyzed jointly. We develop a Bayesian clustering method that analyzes all expressed transcripts and markers jointly in a single model. A transcript may be simultaneously associated with multiple markers. Additionally, a marker may simultaneously alter the expression of multiple transcripts. This is a model-based method that combines a Gaussian mixture of expression data with segregation of multiple linked marker loci. Parameter estimation for each variable is obtained via the posterior mean drawn from a Markov chain Monte Carlo sample. The method allows a regular quantitative trait to be included as an expression trait and subject to the same clustering assignment. If an expression trait links to a locus where a quantitative trait also links, the expressed transcript is considered to be associated with the quantitative trait. The method is applied to a microarray experiment with 60 F(2) mice measured for 25 different obesity-related quantitative traits. In the experiment, approximately 40,000 transcripts and 145 codominant markers are investigated for their associations. A program written in SAS/IML is available from the authors on request.
| S-EPMC1893048 | biostudies-literature
Project description:BackgroundQuantitative real-time PCR (qPCR) has become the "gold standard" for measuring expression levels of individual miRNAs. However, little is known about the validity of reference miRNAs, the improper use of which can result in misleading interpretation of data.ResultsHere we undertook a systematic approach to identify highly stable miRNAs in different stress conditions such as low oxygen (hypoxia), UV-stress and high temperature (heat-stress) in the nematode Caenorhabditis elegans. We conducted genome-wide RNA-seq for small RNAs and selected abundant miRNAs with minimal variation of expression between the different conditions. We further validated the stable expression of a selection of those constitutively expressed candidates in the different stress conditions by SYBR Green qPCR. The selected miRNA candidates were analyzed for stability by applying the widely used geNorm logarithm. With this approach, we were able to successfully identify suitable reference miRNAs for each stress condition. Interestingly, we also found that 3 miRNAs, namely mir-2-5p, mir-46-3p and mir-47-3p, are stable in all the above-mentioned conditions suggesting that they might have general functions independent of stress.ConclusionsOur analysis offers a comprehensive list of stably expressed miRNAs in different stress conditions that can be confidently used as reference miRNAs for qPCR analysis in C. elegans.
| S-EPMC3997968 | biostudies-literature