Snoek, B. L. | Search bioRxiv

bioRxiv2018

A multi-parent recombinant inbred line population of Caenorhabditis elegans enhances mapping resolution and identification of novel QTLs for complex life-history traits

Local populations of the bacterivorous nematode Caenorhabditis elegans can be genetically almost as diverse as global populations. To investigate the effect of local genetic variation on heritable traits, we developed a new recombinant inbred line (RIL) population derived from four wild isolates. The wild isolates were collected from two closely located sites in France: Orsay and Santeuil. By crossing these four genetically diverse parental isolates a population of 200 RILs was constructed. RNA-seq was used to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the four genotypes with an average spacing of 11 kb, possibly doubling the mapping resolution relative to currently available RIL panels. The SNPs were used to construct a genetic map to facilitate QTL analysis. Life history traits, such as lifespan, stress resistance, developmental speed and population growth were measured in different environments. For most traits substantial variation was found, and multiple QTLs could be detected, including novel QTLs not found in previous QTL analysis, for example for lifespan or pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping. Taken together, we show that RNA-seq can be used for genotyping, that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates permits analysis of local adaptation and life history trade-offs.

genetics↗

bioRxiv2017

Genetical genomics reveals Ras/MAPK modifier loci

The oncogenic Ras/MAPK pathway is evolutionary conserved across metazoans and is essential for many cellular functions. Mutant screens in the model nematode Caenorhabditis elegans have been invaluable for elucidating Ras/MAPK pathway characteristics and identification of the genes involved. Almost all of these screens have been conducted in a single genetic background. However, phenotypic traits of induced mutations can vary widely depending on the genetic background. At the moment, we lack insight into how different genetic backgrounds modulate Ras/MAPK-signaling and which genetic modifiers are involved.\n\nWe previously introduced a gain-of-function mutation in the Ras/MAPK pathway gene let-60 in over 200 recombinant inbred lines (mutant introgressed RILs: miRILs) and detected genetic modifiers affecting this pathway by studying variation in vulval development. In the present study, we investigate how gene expression regulation is affected by the let-60 gain-of-function mutation and the genetic background by mapping eQTL using 33 miRILs. We found that the majority ([~]73%) of the 1516 detected cis-eQTL are not specific for the let-60 mutation, whereas most ([~]76%) of the 898 detected trans-eQTL are associated with the let-60 mutation. We detected 6 eQTL trans-bands that were specific for the interaction between the genetic background and the mutation. One of these eQTL hotspots co-localizes with the previously identified polymorphic Ras/MAPK modifier amx-2. Comparing gene expression profiles between transgenic lines expressing either the N2 or the CB4856 alleles of amx-2 showed the involvement of amx-2 in 79% of the trans-eQTLs for genes mapping to this trans-band.\n\nTogether, our results have revealed hidden loci affecting Ras/MAPK signaling using sensitized backgrounds in C. elegans. These loci harbor putative polymorphic modifier genes that would not have been detected using mutant screens in single genetic backgrounds.

genetics↗