Mapping different mouse strains to mm10

Question

[Assa Yeroslaviz]

Hi,

I was wondering if one should be concerned about mapping different strains of mouse genome (e.g. CBA/J and C57BL/6J) to the same mouse genomic sequence e.g. mm10 ( = C57BL/6J).

I know there are differences in the sequences, both in terms of SNPs and indels.

I have found a paper, where they did this kind of mapping for ChIP-Seq analysis. But I am not sure how much this would also apply to single-cell experiments. I would assume that the scRNA-Seq will be more proned to changes/differences in the genomic sequence ( or maybe even bulk-RNA-Seq would be more proned to this than ChIp-Seq).

But I am not sure how severe this would be.

Does anyone has any experience with this kind of analysis?

thanks

[Asaf]

I have experience but I didn't understand your question. Are you asking about how bad is it to map CBA/J to mm10 or should you map to the specific strain genome? Can you elaborate

[Assa Yeroslaviz]

Yes, exactly. I was wondering if there is anything specific I must pay attention to, when doing a single-cell/single-nuclei RNA-Seq experiment with two different mouse strains. Do I need to make sure to map them both to their specific genomic sequence, or would it be good enough to map them both to the same genome, e.g. mm10?

I am asking this, because I know there are differences in the genomic sequence between different strains, but I am not sure how much difference would result in changes in the mapping -> clustering -> etc.

[Asaf]

We've been struggling with this question, mainly in the diversity outbred and collaborative cross mice. Eventually, there is no real difference between the two alternatives. Eventually, the strain will be a major factor in gene expression signature and a gene's expression levels could not be directly compared between the two strains anyway.

[Assa Yeroslaviz]

thanks, I'll take that under consideration.