Mountain JL, Knight A, Jobin M, Gignoux C, Miller A, Lin AA et al.. SNPSTRs: empirically derived, rapidly typed, autosomal haplotypes for inference of population history and mutational processes. Genome Res 12: 1766-1772

Department of Anthropological Sciences, Stanford, California 94305, USA.
Genome Research (Impact Factor: 13.85). 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.

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Available from: Peter A Underhill, Aug 31, 2015
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    • "Several different approaches have been used to solve this problem. For SNPSTRs, Mountain et al. (2002) amplified the STR locus with two differently labelled primers, each designed to match one of the two nucleotides segregating at the flanking SNP, followed by standard fragment sizing on an automated sequencer. This approach is practical only for SNPSTRs (i.e. "
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    ABSTRACT: HapSTRs combine information from a microsatellite (or simple tandem repeat, STR) with one or more single nucleotide polymorphisms in the DNA sequence immediately flanking the STR. These loci may offer increased power for the estimation of demographic parameters, but also present some challenges for data collection and analysis. We describe a process for inferring HapSTR alleles, including the flanking haplotypes, STR alleles and their phase relative to each other, directly from DNA sequence electropherograms of PCR products from heterozygous individuals. Our approach eliminates the need for more costly and time-consuming processes, such as cloning or acrylamide gel electrophoresis to separate alleles prior to sequencing.
    Molecular Ecology Resources 06/2011; 11(6):1068-75. DOI:10.1111/j.1755-0998.2011.03036.x · 5.63 Impact Factor
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    • "Microsatellite variation also can be compared and combined with SNP variation to reconstruct human evolutionary history on different timescales (deKnijff 2000; Mountain et al. 2002; Payseur and Cutter 2006). The development of analytical tools for integrating patterns of polymorphism at loci with contrasting mutation rates and mechanisms will be required for building a synthetic view of human genomic variation in its many forms. "
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    ABSTRACT: Rapid advances in DNA sequencing and genotyping technologies are beginning to reveal the scope and pattern of human genomic variation. Although single nucleotide polymorphisms (SNPs) have been intensively studied, the extent and form of variation at other types of molecular variants remain poorly understood. Polymorphism at the most variable loci in the human genome, microsatellites, has rarely been examined on a genomic scale without the ascertainment biases that attend typical genotyping studies. We conducted a genomic survey of variation at microsatellites with at least three perfect repeats by comparing two complete genome sequences, the Human Genome Reference sequence and the sequence of J. Craig Venter. The genomic proportion of polymorphic loci was 2.7%, much higher than the rate of SNP variation, with marked heterogeneity among classes of loci. The proportion of variable loci increased substantially with repeat number. Repeat lengths differed in levels of variation, with longer repeat lengths generally showing higher polymorphism at the same repeat number. Microsatellite variation was weakly correlated with regional SNP number, indicating modest effects of shared genealogical history. Reductions in variation were detected at microsatellites located in introns, in untranslated regions, in coding exons, and just upstream of transcription start sites, suggesting the presence of selective constraints. Our results provide new insights into microsatellite mutational processes and yield a preview of patterns of variation that will be obtained in genomic surveys of larger numbers of individuals.
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    • "Thus, LD between multiallelic markers may indeed be greater and extend over longer distances than LD among biallelic SNP markers, which was also found in the LD studies in humans (Pritchard and Przeworski, 2001; Varilo et al., 2003) and cattle (Khatkar et al., 2006a, b). In addition, the relatively high rate of mutation in microsatellite markers makes possible the assessment of recently created LD (Mountain et al., 2002). Thus, microsatellite markers will continue to be useful and informative for studies of LD in the wild. "
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    ABSTRACT: Knowledge about the extent and patterns of linkage disequilibrium (LD) can provide important insights into demographic processes and strategies to identify the genetic basis of complex phenotypes in wild populations. However, data on the extent and patterns of LD from non-model vertebrate species from the wild are still scarce. We conducted so far the most extensive and detailed examination of LD in a pedigreed wild bird population using genotypes from 97 autosomal and 6 gonosomal microsatellites and a recently established linkage map of Siberian jays (Perisoreus infaustus). Analysis of syntenic marker pairs showed high levels of LD that extended over tens of centimorgans or several megabases and generally decayed as an increasing function of intermarker distance. In addition, significant LD was also very common between nonsyntenic markers. Patterns of LD varied across different linkage groups possibly because of the differences in chromosomal structure (macro-, micro-, and Z-chromosome). In particular, the level of LD was significantly lower on the Z-chromosome than on the autosomes at comparable genetic distances. In general, the high levels and extent of LD in this population are likely owing to its relatively small size, significant intrapopulation genetic structure, and occurrence of inbreeding. Whatever the cause, the long-range LD between syntenic loci suggests that LD mapping of phenotypic traits in this population using low-density markers maps is feasible. However, the frequent occurrence of LD between nonsyntenic markers suggests that the combined use of linkage and LD methods is needed to reduce the likelihood of false-positive associations between marker loci and traits of ecological and evolutionary interest.
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