Phenotypic variation manifests from either simple (monogenic) or complex (multigenic) traits. Variation due to genetic and environmental influences is important because the ability to produce a range of phenotypes is essential for adaptive evolution. Complex traits are important not only for evolution, but because many diseases are complex traits. The genetic architecture of complex traits can be very multifaceted, with a large number of causal genes each having a small effect on the overall heritability of the trait, and as such our understanding of the genetic architecture and control of complex traits is limited. Complex traits are studied through quantitative trait loci mapping and genome-wide association studies. Since there are a great range of resources available for the nematode Caenorhabditis elegans, this is an appropriate system in which to study the genetic architecture of complex traits. Dauer larvae development represents a suitable complex trait as many of the genes involved and their genetic pathways have been identified. This trait is also important for the clear links between the dauer larvae of free-living species and the infective stages of many parasitic nematodes, and is therefore important as a model complex trait. Dauer larvae are routinely studied under unnatural conditions, with a cohort of aged-matched worms exposed to concentrated pheromone from many worms, conditions that are not obviously ecologically or evolutionally relevant. It is therefore important to understand the dynamics of growing populations in the laboratory both specifically to understand C. elegans, and generally to understand the genetics of complex traits. Methods have been established for the analysis of population growth assays, and experiments to validate this style of assay have been carried out for the analysis of dauer larvae development in a growing population. In this, extensive variation in dauer larvae development between natural wild isolates and the canonical isolate N2 has been shown, variation which has previously not been demonstrated in standard dauer larvae assays. The genetic basis of this variation was also investigated using two Recombinant Inbred Line (RILs) panels made from two distinct parental genotypes of C. elegans, Isogenic Lines (ILs) of C. elegans and also a C. briggsae RIL panel. These analyses revealed that the genetic architecture of dauer larvae development in growing populations is highly complex, with a large number of QTLs affecting this trait. Also, comparison of the results from the different mapping approaches (RILs vs. ILs) revealed variation in their power to detect QTLs, as the ILs were capable of identifying far more QTLs than the RILs. Three candidate genes which have an effect on dauer larvae development in growing populations were identified and analysed. These candidates are npr-1, srg-36 and srg-37, each showing a negative effect on dauer larvae development in a growing population and an allelic effect of variation at npr-1. Together, these results demonstrate that extensive variation in dauer larvae development can be analysed in growing populations, that the underlying genetics can be mapped and that candidate genes can be identified for the underlying regions.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:681255 |
| Date | January 2014 |
| Creators | Green, J. |
| Publisher | Canterbury Christ Church University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://create.canterbury.ac.uk/14316/ |
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