Biology subjects

Stastna, J. J.

Publications and source records attributed to Stastna, J. J..

2 recordsLinked to original sources

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↗

bioRxiv2018

C. elegans genetic background modifies the core transcriptional response in an α-synuclein model of Parkinson’s disease

Accumulation of protein aggregates is a major cause of Parkinsons disease (PD), a progressive neurodegenerative condition that is one of the most common causes of dementia. Transgenic Caenorhabditis elegans worms expressing the human synaptic protein -synuclein show inclusions of aggregated protein and replicate the defining pathological hallmarks of PD. It is however not known how PD progression and pathology differs among individual genetic backgrounds. Here, we compared gene expression patterns, and investigated the phenotypic consequences of transgenic -synuclein expression in five different C. elegans genetic backgrounds. Transcriptome analysis indicates that the effects of -synuclein expression on pathways associated with nutrient storage, lipid transportation and ion exchange depend on the genetic background. The gene expression changes we observe suggest that a range of phenotypes will be affected by -synuclein expression. We experimentally confirm this, showing that the transgenic lines generally show delayed development, reduced lifespan, and an increased rate of matricidal hatching. These phenotypic effects coincide with the core changes in gene expression, linking developmental arrest, mobility, metabolic and cellular repair mechanisms to -synuclein expression. Together, our results show both genotype-specific effects and core alterations in global gene expression and in phenotype in response to -synuclein. We conclude that the PD effects are substantially modified by the genetic background, illustrating that genetic background mechanisms should be elucidated to understand individual variation in PD.

genomics↗