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. 1990 Aug;87(16):6296–6300. doi: 10.1073/pnas.87.16.6296

Haplotype of multiple polymorphisms resolved by enzymatic amplification of single DNA molecules.

G Ruano 1, K K Kidd 1, J C Stephens 1
PMCID: PMC54520  PMID: 1974719

Abstract

We have developed a reliable method for the direct resolution of haplotypes or linkage phase from individuals who are multiply heterozygous in a given genomic region. The method is based on single-molecule dilution (SMD) of genomic template and amplification via biphasic polymerase chain reaction (booster PCR). We have verified the feasibility of the SMD method for a highly polymorphic region within the beta-globin cluster by analysis of triply heterozygous individuals of known haplotype. This approach should be useful in many studies in population or evolutionary genetics and in a variety of clinical settings.

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