Enhancing linkage analysis of complex disorders: an evaluation of high-density genotyping

• Published in: Human molecular genetics 2004-09, Vol.13 (17), p.1943-1949
• Main Authors: Sawcer, Stephen J, Maranian, Mel, Singlehurst, Sara, Yeo, TaiWai, Compston, Alastair, Daly, Mark J, De Jager, Philip L, Gabriel, Stacey, Hafler, David A, Ivinson, Adrian J, Lander, Eric S, Rioux, John D, Walsh, Emily, Gregory, Simon G, Schmidt, Silke, Pericak-Vance, Margaret A, Barcellos, Lisa, Hauser, Stephen L, Oksenberg, Jorge R, Kenealy, Shannon J, Haines, Jonathan L
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chromosome Mapping - methods; Classical genetics, quantitative genetics, hybrids; Evaluation Studies as Topic; Fundamental and applied biological sciences. Psychology; Genetic Markers - genetics; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Humans; Methods, theories and miscellaneous; Microsatellite Repeats - genetics; Molecular and cellular biology; Multiple Sclerosis - genetics; Polymorphism, Single Nucleotide - genetics; United Kingdom
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddh202

To explore the potential value of recently developed high-density linkage mapping methods in the analysis of complex disease we have regenotyped five nuclear families first studied in the 1996 UK multiple sclerosis linkage genome screen, using Applied Biosystems high-density microsatellite linkage mapping set, the Illumina BeadArray™ linkage mapping panel (version 3) and the Affymetrix GeneChip® Human Mapping 10K array. We found that genotyping success, information extraction and genotyping accuracy were improved with all systems. These improvements were particularly marked with the SNP-based methods (Illumina and Affymetrix), with little difference between these. The extent of additional information extracted is considerable, indicating that reanalysis of existing multiplex families using these newer systems would substantially increase power.