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A highly informative SNP linkage panel for human genetic studies

Abstract

We have developed a highly informative set of single-nucleotide polymorphism (SNP) assays designed for linkage mapping of the human genome. These assays were developed on a robust multiplexed assay system to provide a combination of very high accuracy and data completeness with high throughput for linkage studies. The linkage panel is comprised of approximately 4,700 SNPs with 0.39 average minor allele frequency and 624-kb average spacing. Based on almost 2 million genotypes, data quality was shown to be extremely high, with a 99.94% call rate, >99.99% reproducibility and 99.995% genotypes consistent with mendelian inheritance. We constructed a genetic map with an average 1.5-cM resolution using series of 28 CEPH pedigrees. The relative information content of this panel was higher than those of commonly used STR marker panels. The potent combination of this SNP linkage panel with the multiplexed assay system provides a previously unattainable level of performance for linkage studies.

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Figure 1: Distribution of linkage mapping panel loci.
Figure 2: Information content (IC) comparisons.

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Acknowledgements

We would like to thank members of Illumina's scientific operations, laboratory automation systems and integration (LASI), informatics and software development groups for invaluable technical assistance. In addition, we would like to thank P. Ng, S. Kruglyak, D. Barker and J. Stuelpnagel for helpful discussions and review of the manuscript; T. Matise for helpful discussions about constructing the genetic maps and calculating information content; and K. Markianos and L. Kruglyak for Genehunter version 2.1 to accommodate analysis of all SNP loci in our linkage panel.

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Correspondence to Sarah Shaw Murray.

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All authors are employees of Illumina, Inc. and own stock or stock options in the company.

Supplementary information

Supplementary Table 1

Minor allele frequencies by ethnicity. (PDF 356 kb)

Supplementary Table 2

Genetic map summary. (PDF 21 kb)

Supplementary Table 3

Genetic map. (PDF 211 kb)

Supplementary Methods (PDF 15 kb)

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Murray, S., Oliphant, A., Shen, R. et al. A highly informative SNP linkage panel for human genetic studies. Nat Methods 1, 113–117 (2004). https://doi.org/10.1038/nmeth712

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