Published in:
Open Access
01-12-2014 | Oral presentation
Use of animal models for exome prioritization of rare disease genes
Authors:
Damian Smedley, Sebastian Kohler, William Bone, Anika Oellrich, Jules Jacobsen, Kai Wang, Chris Mungall, Nicole Washington, Sebastian Bauer, Dominic Seelow, Peter Krawitz, Cornelius Boerkel, Christian Gilissen, Melissa Haendel, Suzanna E Lewis, Peter N Robinson, Sanger Mouse Genetics Project
Published in:
Orphanet Journal of Rare Diseases
|
Special Issue 1/2014
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Excerpt
Over 100 disease-gene associations have been identified by whole-exome sequencing since the first reports in 2010, leading to a revolution in rare disease-gene discovery [
1,
2]. However, many cases remain unsolved due to the fact that ~100-1000 loss of function, candidate variants remain after removing those deemed as common, low quality or non-pathogenic. In some cases it may be possible to use multiple affected individuals, linkage data, identity-by-descent inference, identification of
de novo heterozygous mutations from trio analysis, or prior knowledge of affected pathways to narrow down to the causative variant [
3]. Where this is not possible or successful, one approach is to use phenotype data to evaluate whether a particular candidate variant is likely to result in the patient’s clinical manifestations. …
