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Genetic Mapping of Evolutionary Developmental Variation using Hybrid Mouse in vitro Crosses

Periodic Reporting for period 4 - HybridMiX (Genetic Mapping of Evolutionary Developmental Variation using Hybrid Mouse in vitro Crosses)

Reporting period: 2020-02-01 to 2020-07-31

The genome is constantly evolving, yet it must maintain essential functions. Studying molecular patterns of evolutionary change within and among taxa can be a powerful way to dissect genome function and genotype-phenotype maps throughout evolution.

Understanding the genetic basis of trait variation has direct impact on health and medicine, conservation and many agricultural practices.

The overall objectives of our work is the development and application a method to greatly accelerate the genetic mapping of traits, using an cell culture based system. We will use this method to understand how genes and their interactions with each other change throughout evolution and how that affects traits.
"We have developed our main technique, called ""in vitro recombination"", in our system. We show that it is possible to perform genetic mapping of species differences in the mouse entirely in a cell culture context, without requiring breeding any mice.

This method is directly applicable also to human-derived induced pluripotent stem cells, suggesting that our method can be applied to help understand disease and health conditions that have a genetic basis.

Our first results are now published in the Proceedings of the National Academy of Sciences, a prestigious international scientific journal, under Lazzarano et al., 2018."
"Until our project it is not been routinely possible to map genetic traits across species barriers in the mouse or mammals. We have achieved initial results suggesting that we can do exactly that.

It is also difficult to generate genetic lines from the mice that contain a great deal of genetic diversity sampled from the laboratory mice and their related relatives. We have been able to generate about 60 lines that carry far greater genetic information than any existing resources.

The method we have developed may be applied to human cell lines. This may allow drug development or other similar applications to be performed safely without using animal testing, while capturing the genetic diversity found in real human populations. This would be a great advance for medicine, especially in the branch referred to as ""personalized medicine"".