title: Haplotype of multiple polymorphisms resolved by enzymatic amplification of single DNA molecules.
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.
authors.affiliation: Department of Human Genetics, Yale University School of Medicine, New Haven, CT 06510.
authors.forename: G
authors.initials: G
authors.lastname: Ruano
authors.forename: K K
authors.initials: KK
authors.lastname: Kidd
authors.forename: J C
authors.initials: JC
authors.lastname: Stephens
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D021141:Nucleic Acid Amplification Techniques; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D005879:Tourette Syndrome / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D015345:Oligonucleotide Probes; D004247:DNA; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases