Abstract
BackgroundGenetic determinism of cranial morphology in the mouse is still largely unknown, despite the localization of putative QTLs and the identification of genes associated with Mendelian skull malformations. To approach the dissection of this multigenic control, we have used a set of interspecific recombinant congenic strains (IRCS) produced between C57BL/6 and mice of the distant species Mus spretus (SEG/Pas). Each strain has inherited 1.3% of its genome from SEG/Pas under the form of few, small-sized, chromosomal segments.ResultsThe shape of the nasal bone was studied using outline analysis combined with Fourier descriptors, and differential features were identified between IRCS BcG-66H and C57BL/6. An F2 cross between BcG-66H and C57BL/6 revealed that, out of the three SEG/Pas-derived chromosomal regions present in BcG-66H, two were involved. Segments on chromosomes 1 (∼32 Mb) and 18 (∼13 Mb) showed additive effect on nasal bone shape. The three chromosomal regions present in BcG-66H were isolated in congenic strains to study their individual effect. Epistatic interactions were assessed in bicongenic strains.ConclusionsOur results show that, besides a strong individual effect, the QTL on chromosome 1 interacts with genes on chromosomes 13 and 18. This study demonstrates that nasal bone shape is under complex genetic control but can be efficiently dissected in the mouse using appropriate genetic tools and shape descriptors.
Highlights
The skull is a complex three-dimensional structure, with features highly adapted to specialized functions
While variations in natural or pedigreed populations have been used for example in plants [1] fishes [2] or primates [3], studies in mice have been made on either F2 progeny [4], or recombinant inbred strains [5], using classical measurements [6], or geometric morphometrics [7,8]
Nasal Bone Shape Nineteen interspecific recombinant congenic strains (IRCS) strains were compared to B6 and SEG/Pas strain for global skull shape
Summary
The skull is a complex three-dimensional structure, with features highly adapted to specialized functions. Several groups have attempted to tackle the complexity of skull shape in mice using different approaches. Compared with segregating populations such as F2s, where every individual carries a unique genotype, recombinant inbred strains allow for replications, since a trait can be measured on a group of genetically identical, sex- and age-matched individuals, buffering between-individual noise. This results in more power for both the identification and precise localization of QTLs. published studies have failed so far to provide small-sized confidence intervals amenable to the positional cloning of underlying genes. Each strain has inherited 1.3% of its genome from SEG/Pas under the form of few, small-sized, chromosomal segments
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