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Nucleic Acids Research Advance Access published online on June 18, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn373
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Methods Online

Long-range, high-throughput haplotype determination via haplotype-fusion PCR and ligation haplotyping

Daniel J. Turner*, Chris Tyler-Smith and Matthew E. Hurles

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK

*To whom correspondence should be addressed. Tel: +44 (0) 1223 494588; Fax: +44 (0) 1223 494919; Email: djt{at}sanger.ac.uk

Received April 2, 2008. Revised May 13, 2008. Accepted May 28, 2008.

Ligation Haplotyping is a robust, novel method for experimental determination of haplotypes over long distances, which can be applied to assaying both sequence and structural variation. The simplicity and efficacy of the method for genotyping large chromosomal rearrangements and haplotyping SNPs over long distances make it a valuable and powerful addition to the methodological repertoire, which will be beneficial to studies of population genetics and evolution, disease association and inheritance, and genomic variation. We illustrate the versatility of the method both by genotyping a Yp paracentric inversion, found in ~60% of Northwest European males, that strongly influences the germline rate of infertility-causing XY translocations and by haplotyping two autosomal SNPs that lie 16.4 kb apart on chromosome 7, and which influence an individual's susceptibility to systemic lupus erythematosus.


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