Abstract:
:Generating human single-nucleotide polymorphisms (SNPs) is no longer a rate-limiting step for genetic studies of disease. The number of SNPs in public databases already exceeds 200,000, and the total is expected to exceed 1,000,000 within a year. Rather, progress is limited by the inability to genotype large numbers of SNPs. Current genotyping methods are suitable for studying individual loci or at most a handful at a time. Here, we describe a method for parallel genotyping of SNPs, called single base extension-tag array on glass slides, SBE-TAGS. The principle is as follows. SNPs are genotyped by single base extension (SBE), using bifunctional primers carrying a unique sequence tag in addition to a locus-specific sequence. Because each locus has a distinct tag, the genotyping reactions can be performed in a highly multiplexed fashion, and the resulting product can then be "demultiplexed" by hybridization to the reverse complements of the sequence tags arrayed on a glass slide. SBE-TAGS is simple and inexpensive because of the high degree of multiplexing and the use of an easily generated, generic tag array. The method is also highly accurate: we genotyped over 100 SNPs, obtaining over 5, 000 genotypes, with approximately 99% accuracy.
journal_name
Proc Natl Acad Sci U S Aauthors
Hirschhorn JN,Sklar P,Lindblad-Toh K,Lim YM,Ruiz-Gutierrez M,Bolk S,Langhorst B,Schaffner S,Winchester E,Lander ESdoi
10.1073/pnas.210394597keywords:
subject
Has Abstractpub_date
2000-10-24 00:00:00pages
12164-9issue
22eissn
0027-8424issn
1091-6490pii
210394597journal_volume
97pub_type
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