Article

SNPSTRs: Empirically Derived, Rapidly Typed, Autosomal Haplotypes for Inference of Population History and Mutational Processes

Department of Anthropological Sciences, Stanford, California 94305, USA.
Genome Research (Impact Factor: 14.63). 12/2002; 12(11):1766-72. DOI: 10.1101/gr.238602
Source: PubMed

ABSTRACT

Each independently evolving segment of the genomes of a sexually reproducing organism has a separate history reflecting part of the evolutionary history of that organism. Uniparentally or clonally inherited DNA segments such as the mitochondrial and chloroplast genomes and the nonrecombining portion of the Y chromosome have provided, to date, most of the known data regarding compound haplotypic variation within and among populations. These comparatively small segments include numerous polymorphic sites and undergo little or no recombination. Recombining autosomes, however, comprise the major repository of genetic variation. Technical challenges and recombination have limited large-scale application of autosomal haplotypes. We have overcome this barrier through development of a general approach to the assessment of short autosomal DNA segments. Each such segment includes one or more single nucleotide polymorphisms (SNPs) and exactly one short tandem repeat (STR) locus. With dramatically different mutation rates, these two types of genetic markers provide complementary evolutionary information. We call the combination of a SNP and a STR polymorphism a SNPSTR, and have developed a simple, rapid method for empirically determining gametic phase for double and triple heterozygotes. Here, we illustrate the approach with two SNPSTR systems. Although even one system provides insight into population history, the power of the approach lies in combining results from multiple SNPSTR systems.

    • "Flanking region polymorphisms may also aid our understanding of mutational events and the evolutionary history of these loci [29] [66] [101] [102]. These polymorphisms may be present in the form of " microhaplotypes " , recently described in forensic literature as genomic regions containing two to four SNPs within 200 bp, with those of particular forensic interest being characterized as highly heterozygous and statistically independent [103]. "
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    ABSTRACT: The development of next generation sequencing (NGS) technologies creates the potential for changing the method by which the forensic science community genotypes short tandem repeat (STR) loci. While the capabilities of NGS are promising, moving from current capillary electrophoresis (CE) methods would require new guidelines to be established and a new understanding of artifacts that may arise with the use of NGS. Stutter has been well characterized for CE technologies; however, NGS workflows may use different polymerases and amplification approaches, which could alter the appearance of this artifact. Stutter is most commonly seen in the n-4 position in CE data, but may be observed more rarely in the n+4 and n-8 positions. NGS data frequently contains detectable sequences consistent with stutter at the n+4 and n-8 positions, and may even contain stutter at the n-12 position for some loci. It is possible that these alternate types of stutter events occur at similar levels in CE workflows and go undetected due to the analytical threshold employed or because the artifacts do not exceed the background noise. Comparing stutter events in NGS data to what has been observed by CE will improve our understanding of the effects of library preparation and sequencing. Characterizing stutter events by sequence will contribute to the development of guidelines and facilitate implementation of NGS technology. Further, determining stutter ratios for each isoallele would allow for individual sequence thresholds to be set, which could then be used to improve mixture interpretation models.
    No preview · Article · Sep 2015 · Forensic Science International Genetics Supplement Series
    • "Flanking region polymorphisms may also aid our understanding of mutational events and the evolutionary history of these loci [29] [66] [101] [102]. These polymorphisms may be present in the form of " microhaplotypes " , recently described in forensic literature as genomic regions containing two to four SNPs within 200 bp, with those of particular forensic interest being characterized as highly heterozygous and statistically independent [103]. "
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    ABSTRACT: This article reviews what is currently known about short tandem repeat (STR) allelic sequence variation in and around the twenty-four loci most commonly used throughout the world to perform forensic DNA investigations. These STR loci include D1S1656, TPOX, D2S441, D2S1338, D3S1358, FGA, CSF1PO, D5S818, SE33, D6S1043, D7S820, D8S1179, D10S1248, TH01, vWA, D12S391, D13S317, Penta E, D16S539, D18S51, D19S433, D21S11, Penta D, and D22S1045. All known reported variant alleles are compiled along with genomic information available from GenBank, dbSNP, and the 1000 Genomes Project. Supplementary files are included which provide annotated reference sequences for each STR locus, characterize genomic variation around the STR repeat region, and compare alleles present in currently available STR kit allelic ladders. Looking to the future, STR allele nomenclature options are discussed as they relate to next generation sequencing efforts underway. Published by Elsevier Ireland Ltd.
    No preview · Article · Jul 2015 · Forensic Science International: Genetics
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    • "APOE isoforms were coded by the rs429358 and rs7412 genotypes. Ten STRs were selected after scanning the APOE/C1/C4/C2 region with the UCSC Genome Browser (http://genome.ucsc.edu/cgibin/hgGateway ) and the SNPSTR database (Mountain et al., 2002). Details on the analysed SNPs and STRs are described in Tables 1 and 2. "
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    ABSTRACT: The APOE/C1/C4/C2 gene cluster presents high relevance in lipid metabolism and, therefore, has important epidemiological implications. Here, we study for the first time the variation patterns of 25 polymorphisms (10 short tandem repeats, STRs, and 15 single nucleotide polymorphismas, SNPs) in two native Andean samples from Bolivia (45 Aymaras and 45 Quechuas) as well as one European sample (n = 41) as external reference. We estimated diversity parameters, linkage disequilibrium patterns, population structure, and possible selective effects. In general, diversity was low and could be partly attributed to selection (probably due to its physiological importance), since the APOE/C1/C4/C2 region was highly conserved compared to the flanking genes in both Bolivians and Europeans. Moreover, the lower gene diversity in Bolivians compared to Europeans for some markers might indicate different demographic histories. Regarding the APOE isoforms, in addition to ɛ3 (94%) and ɛ4 (5%), isoform ɛ2 (1%) was also detected in Bolivians. In relation to previous hypotheses, our results support that genetic drift or founder effects rather than selection for increased cholesterol absorption are the main factors that have shaped the distribution of APOE isoforms observed in South America.
    Full-text · Article · Jul 2012 · Annals of Human Genetics
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