title: Current sequencing technology makes microhaplotypes a powerful new type of genetic marker for forensics.
abstract: SNPs that are molecularly very close (<10kb) will generally have extremely low recombination rates, much less than 10(-4). Multiple haplotypes will often exist because of the history of the origins of the variants at the different sites, rare recombinants, and the vagaries of random genetic drift and/or selection. Such multiallelic haplotype loci are potentially important in forensic work for individual identification, for defining ancestry, and for identifying familial relationships. The new DNA sequencing capabilities currently available make possible continuous runs of a few hundred base pairs so that we can now determine the allelic combination of multiple SNPs on each chromosome of an individual, i.e., the phase, for multiple SNPs within a small segment of DNA. Therefore, we have begun to identify regions, encompassing two to four SNPs with an extent of <200bp that define multiallelic haplotype loci. We have identified candidate regions and have collected pilot data on many candidate microhaplotype loci. Here we present 31 microhaplotype loci that have at least three alleles, have high heterozygosity, are globally informative, and are statistically independent at the population level. This study of microhaplotype loci (microhaps) provides proof of principle that such markers exist and validates their usefulness for ancestry inference, lineage-clan-family inference, and individual identification. The true value of microhaplotypes will come with sequencing methods that can establish alleles unambiguously, including disentangling of mixtures, because a single sequencing run on a single strand of DNA will encompass all of the SNPs.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA. Electronic address: Kenneth.Kidd@yale.edu.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Kidd
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pakstis
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Speed
authors.affiliation: Human Identification Group, Thermo Fisher Scientific, 180 Oyster Point Blvd., South San Francisco, CA 94080, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Lagacé
authors.affiliation: Human Identification Group, Thermo Fisher Scientific, 180 Oyster Point Blvd., South San Francisco, CA 94080, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Chang
authors.affiliation: Human Identification Group, Thermo Fisher Scientific, 180 Oyster Point Blvd., South San Francisco, CA 94080, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Wootton
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Haigh
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Kidd
mesh_terms: D053803:Forensic Genetics; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers
keywords: AIMs; AISNPs; Ancestry; Lineage; Microhaplotypes; SNPs