DNAprint Genomics (DNAG)

[mingwan0]

Robert, one of the most interesting connections in the Affymetrix work is of course the following:

http://www.ingenta.com/isis/searching/Expand/ingenta?pub=infobike://hsp/hg/2004/00000001/00000004/ar...

The genomic distribution of population substructure in four populations using 8,525 autosomal SNPs

Human Genomics May 2004, vol. 1, no. 4, pp. 274-286(13)

Shriver M.D.[1]; Kennedy G.C.[2]; Parra E.J.[3]; Lawson H.A.[1]; Sonpar V.[1]; Huang J.[2]; Akey J.M.[4]; Jones K.W.[2]

[1] Penn State University, University Park, Pennsylvania, USA [2] Affymetrix, Inc., Santa Clara, California, USA [3] University of Toronto at Mississauga, Mississauga, Canada [4] Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Abstract:
Understanding the nature of evolutionary relationships among persons and populations is important for the efficient application of genome science to biomedical research. We have analysed 8,525 autosomal single nucleotide polymorphisms (SNPs) in 84 individuals from four populations: African-American, European-American, Chinese and Japanese. Individual relationships were reconstructed using the allele sharing distance and the neighbour-joining tree making method. Trees show clear clustering according to population, with the root branching from the African-American clade. The African-American cluster is much less star-like than European-American and East Asian clusters, primarily because of admixture. Furthermore, on the East Asian branch, all ten Chinese individuals cluster together and all ten Japanese individuals cluster together. Using positional information, we demonstrate strong correlations between inter-marker distance and both locus-specific FST (the proportion of total variation due to differentiation) levels and branch lengths. Chromosomal maps of the distribution of locus-specific branch lengths were constructed by combining these data with other published SNP markers (total of 33,704 SNPs). These maps clearly illustrate a non-uniform distribution of human genetic substructure, an instructional and useful paradigm for education and research.

Keywords: population genomics; population genetics; microarray; genotyping; evolution; admixture

Document Type: Research article ISSN: 1473-9542

SICI (online): 1473-9542(20040501)1:4L.274;1-

Matsuzaki H, Loi H, Dong S, Tsai YY, Fang J, Law J, Di X, Liu WM, Yang G, Liu G, Huang J, Kennedy GC, Ryder TB, Marcus GA, Walsh PS, Shriver MD, Puck JM, Jones KW, Mei R.

Parallel genotyping of over 10,000 SNPs using a one-primer assay on a high-density oligonucleotide array.

Genome Res. 2004 Mar;14(3):414-25.

Affymetrix, Inc., Santa Clara, California 95051, USA.

The analysis of single nucleotide polymorphisms (SNPs) is increasingly utilized to investigate the genetic causes of complex human diseases. Here we present a high-throughput genotyping platform that uses a one-primer assay to genotype over 10,000 SNPs per individual on a single oligonucleotide array. This approach uses restriction digestion to fractionate the genome, followed by amplification of a specific fractionated subset of the genome. The resulting reduction in genome complexity enables allele-specific hybridization to the array. The selection of SNPs was primarily determined by computer-predicted lengths of restriction fragments containing the SNPs, and was further driven by strict empirical measurements of accuracy, reproducibility, and average call rate, which we estimate to be >99.5%, >99.9%, and>95%, respectively [corrected]. With average heterozygosity of 0.38 and genome scan resolution of 0.31 cM, the SNP array is a viable alternative to panels of microsatellites (STRs). As a demonstration of the utility of the genotyping platform in whole-genome scans, we have replicated and refined a linkage region on chromosome 2p for chronic mucocutaneous candidiasis and thyroid disease, previously identified using a panel of microsatellite (STR) markers.

http://egweb.bcgsc.ca/journal_club/2003_2004/pdfs/journal_club_040322.pdf