Phenotypic variability and genetic architecture of limbs in populations and strains of the house mouse (Mus musculus)

Škrabar, Neva

The present thesis addresses the variability and genetic basis of limb bone length phenotypes in different populations and strains of the house mouse (Mus musculus). The first two chapters investigate mainly questions of developmental architecture. Chapter one observes the degree of fluctuating asymmetry (FA), reflected in non-directional differences between right and left sides of paired bilateral characters. The lowest level of FA was found in the mice from the hybrid zone and the highest in the inbred strain. Moreover, the level of FA was not affected by the degree of hybridization. The second chapter examines covariation between limb bone lengths, which is commonly observed through morphological integration based on shared functional and developmental connections among different structures. Higher degree of integration was found in the hybrid group, implying on stronger influence of stabilizing selection, whereas outbred populations and inbred strains did not show larger differences. The third chapter constitutes an approach to map genetic factors that generate limb variation and considers genetic variation that can affect multiple traits. In this part of the study, only mice from the hybrid zone were used. Based on the results from the second chapter which showed high phenotypic correlations, special interest was in developmentally and functionally related traits that could have common genetic variants underlying these complex structures. Overall, these traits revealed high heritability explained by genotyped markers, as well as a polygenic genetic architecture. Candidate genes previously described in limb and bone formation were identified together with genetic variants that were not previously reported in QTL studies of this phenotype. Further, genetic regions associated with different bones were found, as well as high genetic correlations between the bones that share developmental mechanisms, i.e. serially homologous structures.

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Škrabar, Neva: Phenotypic variability and genetic architecture of limbs in populations and strains of the house mouse (Mus musculus).

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