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Nucleic Acids Research 2004 32(20):e164; doi:10.1093/nar/gnh163
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Published online 23 November 2004

Nucleic Acids Research, Vol. 32 No. 20 © Oxford University Press 2004; all rights reserved

Genomewide linkage searches for Mendelian disease loci can be efficiently conducted using high-density SNP genotyping arrays

Gabrielle S. Sellick, Cheryl Longman1, John Tolmie1, Ruth Newbury-Ecob2, Lynn Geenhalgh2, Simon Hughes, Margo Whiteford1, Christine Garrett3 and Richard S. Houlston*

Section of Cancer Genetics, Institute of Cancer Research, Sutton, SM2 5NG, UK, 1 Department of Clinical Genetics, Royal Hospital for Sick Children, Glasgow, G3 8SJ, UK, 2 Department of Clinical Genetics, The United Bristol Healthcare NHS Trust, Bristol, BS2 8EG, UK and 3 North West Thames Regional Genetics Service, Kennedy-Galton Centre, North West London Hospitals NHS Trust, Harrow, HA1 3UJ, UK

* To whom correspondence should be addressed. Tel: +44 208 722 4175; Fax: +44 208 722 4362; Email: richard.houlston{at}icr.ac.uk
+NM_003989, NP_003980, NP_035167, S23341, CAB09696, AAL04157

Received July 6, 2004; Revised October 14, 2004; Accepted November 2, 2004

Genomewide linkage searches aimed at identifying disease susceptibility loci are generally conducted using 300–400 microsatellite markers. Genotyping bi-allelic single nucleotide polymorphisms (SNPs) provides an alternative strategy. The availability of dense SNP maps coupled with recent technological developments in highly paralleled SNP genotyping makes it practical to now consider the use of these markers for whole-genome genetic linkage analyses. Here, we report the findings from three successful genomewide linkage analyses of families segregating autosomal recessively inherited neonatal diabetes, craniosynostosis and dominantly inherited renal dysplasia using the Affymetrix 10K SNP array. A single locus was identified for each disease state, two of which are novel. The performance of the SNP array, both in terms of efficiency and precision, indicates that such platforms will become the dominant technology for performing genomewide linkage searches.


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