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Nucleic Acids Research, 2002, Vol. 30, No. 15 e76
© 2002 Oxford University Press

An efficient haplotyping method with DNA pools

Ester Inbar1, Benjamin Yakir2 and Ariel Darvasi*,1,3

1 Life Sciences Institute, Givat-Ram, The Hebrew University of Jerusalem, 2 Department of Statistics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel and 3 IDgene Pharmaceuticals Ltd Bet Offer, Nahum Hafzadi 5, Jerusalem 91344, Israel

*To whom correspondence should be addressed at: Life Sciences Institute, Givat-Ram, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. Tel: +972 2 6584298; Fax: +972 2 5671179; Email: arield{at}cc.huji.ac.il

Determination of haplotype frequencies (the joint distribution of genetic markers) in large population samples is a powerful tool for association studies. This is due to their greater extent of polymorphism since any two bi-allelic single nucleotide polymorphisms (SNPs) generate a potential four-allele genetic marker. Therefore, a haplotype may capture a given functional polymorphism with higher statistical power than its SNP components. The statistical estimation of haplotype frequencies, usually employed in linkage disequilibrium studies, requires individual genotyping for each SNP in the haplotype, thus making it an expensive process. In this study, we describe a new method for direct measurement of haplotype frequencies in DNA pools by allele-specific, long-range haplotype amplification. The proposed method allows the efficient determination of haplotypes composed of two SNPs in close vicinity (up to 20 kb).


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