Morphometric properties and quantitative trait loci mapping of the mouse limb skeleton

The skeleton of vertebrates is a complex biological system, in which the morphometric properties of each bone reflect species’ adaptation to their unique ecological niche. In most tetrapods, the front and hind limbs exhibit a modular pattern that is conserved among species. This pattern involves the long bones: the humerus and femur form the stylopod, while radius, ulna, fibula and tibia make up the zeugopod part. The morphometric correlation of same module bones reflects their shared function in achieving gait. However, in many species limbs have evolved to fullfil more diverse roles, such as digging, swimming or jumping. In murine rodents, such as house mouse the front limb is specialised not only for walking, but also for grooming or feeding. These diverse roles lead to changes in the correlation patterns between same module bones. Importantly, it has been previously shown, that not only length but also proportions of limb bones are complex traits controlled by multiple genetic regions. Genes from the Sox family play a crucial role in chondrogenesis, whereas cadherin protein coding genes influence tissue diversification. Although these, and several other genes have already been identified as affecting the diversification of bone proportions, the full picture of vertebrate limb evolution remains poorly understood. I used the advanced intercross mouse population, called the G15 to further explore genetic basis of bone morphometric properties. Thanks to a large number of recombination events in this long-maintained population, as well as using dense genotyping array, I identified new regions linked to the lengths and proportions of limb bones, and I narrowed down regions found in previous mapping attempts. Newly found candidate genes might provide excellent ground for the future functional genetic studies.


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