Dataset Information

A genomic portrait of human microsatellite variation.

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.

SUBMITTER: Payseur BA

PROVIDER: S-EPMC3002246 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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A genomic portrait of human microsatellite variation.

Payseur Bret A BA Jing Peicheng P Haasl Ryan J RJ

Molecular biology and evolution 20100730 1

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 studi ...[more]

PMID: 20675409

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Project description:BackgroundMicrosatellites are frequently used genetic markers in a wide range of applications, primarily due to their high length polymorphism levels that can easily be genotyped by fragment length analysis. However, the mode of microsatellite evolution is yet not fully understood, and the role of interrupting motifs for the stability of microsatellites remains to be explored in more detail. Here we present a sequence analysis of mutation events and a description of the structure of repeated regions in the hypervariable, pentanucleotide microsatellite locus HrU10 in barn swallows (Hirundo rustica) and tree swallows (Tachycineta bicolor).ResultsIn a large-scale parentage analysis in barn swallows and tree swallows, broods were screened for mutations at the HrU10 locus. In 41 cases in the barn swallows and 15 cases in the tree swallows, mutations corresponding to the loss or gain of one or two repeat units were detected. The parent and mutant offspring alleles were sequenced for 33 of these instances (26 in barn swallows and 7 in tree swallows). Replication slippage was considered the most likely mutational process. We tested the hypothesis that HrU10, a microsatellite with a wide allele size range, has an increased probability of introductions of interruptive motifs (IMs) with increasing length of the repeated region. Indeed, the number and length of the IMs was strongly positively correlated with the total length of the microsatellite. However, there was no significant correlation with the length of the longest stretch of perfectly repeated units, indicating a threshold level for the maximum length of perfectly repeated pentanucleotide motifs in stable HrU10 alleles. The combination of sequence and pedigree data revealed that 15 barn swallow mutations (58%) produced alleles that were size homoplasic to other alleles in the data set.ConclusionOur results give further insights into the mode of microsatellite evolution, and support the assumption of increased slippage rate with increased microsatellite length and a stabilizing effect of interrupting motifs for microsatellite regions consisting of perfect repeats. In addition, the observed extent of size homoplasy may impose a general caution against using hypervariable microsatellites in genetic diversity measures when alleles are identified by fragment length analysis only.

Dataset Information

A genomic portrait of human microsatellite variation.

Publications

A genomic portrait of human microsatellite variation.

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