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Systems genetics links Bicc1 to bone development

Nature Reviews Endocrinology volume 10, page 380 (2014)Cite this article

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In their previous work, the researchers used linkage analysis to identify quantitative trait loci (QTLs) for BMD in a cross between mice with low bone mass and mice with high bone mass. In the new study, the team used a systems genetics approach to identify the gene responsible for a BMD-associated QTL on mouse chromosome 10. As Farber explains, “systems genetics studies seek to identify genetic variation that influences gene expression and then use this information to more rapidly identify the subset of variation that contributes to disease”.

The researchers used microarray analysis to identify a subset of genes located on chromosome 10 whose transcript levels were influenced by local genetic variation and whose expression correlated with BMD. Nine genes fitting these criteria were identified, of which only Bicc1 was predicted by causality modelling to be responsible for the change in BMD. To validate this prediction in vivo, the researchers studied Bicc1-deficient mice. As Bicc1−/− mice develop severe early-onset PKD and die shortly after birth, the team used Bicc1+/− mice. BMD was significantly lower in Bicc1+/− mice than in their wild-type littermates, confirming that Bicc1 is a genetic determinant of BMD.

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References

  1. Mesner, L. D. et al. Bicc1 is a genetic determinant of osteoblastogenesis and bone mineral density. J. Clin. Invest. 10.1172/JCI73072

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  1. David Holmes
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Holmes, D. Systems genetics links Bicc1 to bone development. Nat Rev Endocrinol 10, 380 (2014). https://doi.org/10.1038/nrendo.2014.77

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