Journal article
Reducing the exome search space for Mendelian diseases using genetic linkage analysis of exome genotypes
KR Smith, CJ Bromhead, MS Hildebrand, AE Shearer, PJ Lockhart, H Najmabadi, RJ Leventer, G McGillivray, DJ Amor, RJ Smith, M Bahlo
Genome Biology | Published : 2011
Abstract
Many exome sequencing studies of Mendelian disorders fail to optimally exploit family information. Classical genetic linkage analysis is an effective method for eliminating a large fraction of the candidate causal variants discovered, even in small families that lack a unique linkage peak. We demonstrate that accurate genetic linkage mapping can be performed using SNP genotypes extracted from exome data, removing the need for separate array-based genotyping. We provide software to facilitate such analyses. © 2011 Smith et al.; licensee BioMed Central Ltd.
Grants
Awarded by National Institute of General Medical Sciences
Funding Acknowledgements
We acknowledge Kate Pope, Hayley Mountford and Elizabeth Fitzpatrick (Accelerated Gene Identification Project, Murdoch Childrens Research Institute) for assistance with families A, T and M. This work was supported by an Australian Research Council (ARC) Future Fellowship (MB), an NHMRC Program Grant (MB, DJA), NIH-NIDCD grant RO1 DCOO2842 (RJHS), NHMRC overseas biomedical postdoctoral training fellowship 546943 (MSH), a Doris Duke Fellowship (AES) and the Victorian Government's Operational Infrastructure Support Program (PL, RJL, GM, DJA). Funding sources had no role any of the following: design of the study; the collection, analysis, and interpretation of data; the writing of the manuscript; and the decision to submit the manuscript for publication.