The IMPC aids the functional annotation of genes in wild species

• The IMPC has focused on translating knowledge from mouse to human, to identify models for human disease. However, translating to other species is relevant as well
• Genetic functional data from the IMPC is relevant to identify genes essential for development or associated to disease or adaptation in other species
• The type of analyses presented here could be used to improve the breeding management of endangered mammals

Approach

We used IMPC data derived from the IMPC Viability Primary Screen [IMPC_VIA_001] to identify genes essential for organismal viability (development and survival) collected up to DR 7.0., as well as all phenotype associations collected by the IMPC up to DR 6.2. We used these data in combination with (human) cell viability data to inform wild species genomic data sets collected from the literature.

IMPC Conservation Publication

Aiding the functional annotation of genes relevant for development and adaptation in mammalian species

Conservation Genetics Special Issue on Adaptation
Supplementary Material

• We used IMPC organism viability data in combination with human cell viability data to identify essential genes.
• Genes in gorillas with loss-of-function (LoF) alleles have been previously identified; we inferred gorilla-to-mouse and gorilla-to-human orthologues of those genes and associated them to genes essential for organism and cell viability.
• For this set of genes with LoF alleles, we found that the percentage of lethal/essential genes was lower than for protein-coding genes, but the difference was not significant (P > 0.1 in all comparisons).
• Future research may include improved methods to detect LoF variants, detailed observation of gorillas carrying these variants, investigating whether the LoF variants affect or not the functional exons, and whether there are paralogues or alternative genes providing functional compensation.
• We also show how phenotype associations collected by the IMPC can aid the functional annotation of regions putatively targeted by positive selection or associated to disease using examples from wild species, such as polar bears and cheetahs.
• This investigation is based on about 15% of mammalian protein-coding genes. The IMPC continues screening for genes essential for organism survival and development and collecting phenotype association data.

Methods

• We developed custom scripts to infer orthologues based on available resources (HGNC Comparison of Orthology Predictions (HCOP), MetaPhOrs) and to conduct gene overlaps
• We collected IMPC primary viability screen data and combined it with human cell viability data from 3 different studies (Blomen et al. 2015; Hartl et al. 2015; Wang et al. 2015) to identify essential genes in cells and in mouse (for data, see Supplementary Material)
• We collected IMPC phenotype annotations (also MGI) to characterize genes potentially linked to disease or to regions putatively under positive selection in selected endangered species (for data, see Supplementary Material)

IMPC significant phenotypes

IMPC significant phenotypes for selected mammal species, based on orthologue inferences (source: IMPC Conservation Genetics paper). Note links are to phenotype pages depicting data as in the current Data Release.