Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Sep 14;12(9):R85.
doi: 10.1186/gb-2011-12-9-r85.

Reducing the exome search space for mendelian diseases using genetic linkage analysis of exome genotypes

Katherine R Smith  1 , Catherine J Bromhead, Michael S Hildebrand, A Eliot Shearer, Paul J Lockhart, Hossein Najmabadi, Richard J Leventer, George McGillivray, David J Amor, Richard J Smith, Melanie Bahlo
Affiliations

Reducing the exome search space for mendelian diseases using genetic linkage analysis of exome genotypes

Katherine R Smith et al. Genome Biol. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Partial pedigrees for families A, T and M.
Figure 2
Figure 2
Genome-wide comparison of LOD scores using array-based and WES-derived genotypes for families A, T and M.
See this image and copyright information in PMC

References

    1. Durbin RM, Abecasis GR, Altshuler DL, Auton A, Brooks LD, Gibbs RA, Hurles ME, McVean GA. 1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature. 2010;467:1061–1073. doi: 10.1038/nature09534. - DOI - PMC - PubMed
    1. Johnson JO, Mandrioli J, Benatar M, Abramzon Y, Van Deerlin VM, Trojanowski JQ, Gibbs JR, Brunetti M, Gronka S, Wuu J, Ding J, McCluskey L, Martinez-Lage M, Falcone D, Hernandez DG, Arepalli S, Chong S, Schymick JC, Rothstein J, Landi F, Wang Y-D, Calvo A, Mora G, Sabatelli M, Monsurrò, Rosaria Maria, Battistini S, Salvi F, Spataro R, Sola P, Borghero G. et al.Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS. Neuron. 2010;68:857–864. doi: 10.1016/j.neuron.2010.11.036. - DOI - PMC - PubMed
    1. Wang JL, Yang X, Xia K, Hu ZM, Weng L, Jin X, Jiang H, Zhang P, Shen L, Feng Guo J, Li N, Li YR, Lei LF, Zhou J, Du J, Zhou YF, Pan Q, Wang J, Wang J, Li RQ, Tang BS. TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain. 2010;133:3510–3518. doi: 10.1093/brain/awq323. - DOI - PubMed
    1. Southgate L, Machado RD, Snape KM, Primeau M, Dafou D, Ruddy DM, Branney PA, Fisher M, Lee GJ, Simpson MA, He Y, Bradshaw TY, Blaumeiser B, Winship WS, Reardon W, Maher ER, FitzPatrick DR, Wuyts W, Zenker M, Lamarche-Vane N, Trembath RC. Gain-of-Function Mutations of ARHGAP31, a Cdc42/Rac1 GTPase Regulator, Cause Syndromic Cutis Aplasia and Limb Anomalies. The American Journal of Human Genetics. 2011;88:574–585. doi: 10.1016/j.ajhg.2011.04.013. - DOI - PMC - PubMed
    1. Bilguvar K, Ozturk AK, Louvi A, Kwan KY, Choi M, Tatli B, Yalnizoglu D, Tuysuz B, Caglayan AO, Gokben S, Kaymakcalan H, Barak T, Bakircioglu M, Yasuno K, Ho W, Sanders S, Zhu Y, Yilmaz S, Dincer A, Johnson MH, Bronen RA, Kocer N, Per H, Mane S, Pamir MN, Yalcinkaya C, Kumandas S, Topcu M, Ozmen M, Sestan N. et al.Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature. 2010;467:207–210. doi: 10.1038/nature09327. - DOI - PMC - PubMed

Publication types