High resolution analysis of bacterial GWAS signals in the mouse and human genomes

Associated Principal Investigator

Background and current state of research

Currently, great effort is being focused on the description and comprehension of the structure, function and evolution of the mammalian gut microbiome. Despite extensive research, little is known about bacterial diversity at the species level and the factors, such as host genetics, that influence microbial traits. During my project, I will be involved in the evaluation and characterization of candidate bacterial taxa displaying host genetic associations at the species/strain level.

Our goals

The goal of this research is to define more precisely the underlying basis of host gene-microbe associations.

How to get there

Next-generation sequencing-based approaches have extended the scope of culture-independent analyses of bacterial communities to unprecedented levels, such as enabling genome-wide association analyses for host genetic factors influencing these communities. However, precise identification of microbial traits cannot reach levels of resolution higher than genus-level classification due to constraints in 16S rRNA gene sequence read length (typically, a max. of a few hundred base-pairs). To characterize genetic associations at the bacterial species level, I will develop group-specific primers for longer 16S rRNA gene fragments at the genus and family levels for promising candidate taxa, such as the genus Bacteroides. I will amplify and sequence near full-length 16S-rRNA genes using Sanger sequencing. This will be performed on human feces and feces from M. m. domesticus- M.m. musculus house mouse subspecies.