| First Author | Ramsbottom SA | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 2 | Pages | 1113-1118 |
| PubMed ID | 31879347 | Mgi Jnum | J:283231 |
| Mgi Id | MGI:6386259 | Doi | 10.1073/pnas.1912602117 |
| Citation | Ramsbottom SA, et al. (2020) Mouse genetics reveals Barttin as a genetic modifier of Joubert syndrome. Proc Natl Acad Sci U S A 117(2):1113-1118 |
| abstractText | Genetic and phenotypic heterogeneity and the lack of sufficiently large patient cohorts pose a significant challenge to understanding genetic associations in rare disease. Here we identify Bsnd (alias Barttin) as a genetic modifier of cystic kidney disease in Joubert syndrome, using a Cep290-deficient mouse model to recapitulate the phenotypic variability observed in patients by mixing genetic backgrounds in a controlled manner and performing genome-wide analysis of these mice. Experimental down-regulation of Bsnd in the parental mouse strain phenocopied the severe cystic kidney phenotype. A common polymorphism within human BSND significantly associates with kidney disease severity in a patient cohort with CEP290 mutations. The striking phenotypic modifications we describe are a timely reminder of the value of mouse models and highlight the significant contribution of genetic background. Furthermore, if appropriately managed, this can be exploited as a powerful tool to elucidate mechanisms underlying human disease heterogeneity. |
