Autoregressive Models for Spectral Analysis of Short Tandem Repeats in DNA Sequences

Author(s):  
Hongxia Zhou ◽  
Hong Yan
Author(s):  
Pierre Murat ◽  
Guillaume Guilbaud ◽  
Julian E. Sale

AbstractBackgroundShort tandem repeats (STRs) contribute significantly to de novo mutagenesis, driving phenotypic diversity and genetic disease. Although highly diverse, their repetitive sequences induce DNA polymerase slippage and stalling, leading to length and sequence variation. However, current studies of DNA synthesis through STRs are restricted to a handful of selected sequences, limiting our broader understanding of their evolutionary behaviour and hampering the characterisation of the determinants of their abundance and stability in eukaryotic genomes.ResultsWe perform a comprehensive analysis of DNA synthesis at all STR permutations and interrogate the impact of STR sequence and secondary structure on their genomic representation and mutability. To do so, we developed a high-throughput primer extension assay that allows monitoring of the kinetics and fidelity of DNA synthesis through 20,000 sequences comprising all STR permutations in different lengths. By combining these measurements with population-scale genomic data, we show that the response of a model replicative DNA polymerase to variously structured DNA is sufficient to predict the complex genomic behaviour of STRs, including abundance and mutational constraints. We demonstrate that DNA polymerase stalling at DNA structures induces error-prone DNA synthesis, which constrains STR expansion.ConclusionsOur data support a model in which STR length in eukaryotic genomes results from a balance between expansion due to polymerase slippage at repeated DNA sequences and point mutations caused by error-prone DNA synthesis at DNA structures.


1997 ◽  
Vol 45 (3) ◽  
pp. 265-270 ◽  
Author(s):  
Anna Pérez-Lezaun ◽  
Francesc Calafell ◽  
Mark Seielstad ◽  
Eva Mateu ◽  
David Comas ◽  
...  

Genetics ◽  
2000 ◽  
Vol 155 (4) ◽  
pp. 1973-1980
Author(s):  
Jinko Graham ◽  
James Curran ◽  
B S Weir

Abstract Modern forensic DNA profiles are constructed using microsatellites, short tandem repeats of 2–5 bases. In the absence of genetic data on a crime-specific subpopulation, one tool for evaluating profile evidence is the match probability. The match probability is the conditional probability that a random person would have the profile of interest given that the suspect has it and that these people are different members of the same subpopulation. One issue in evaluating the match probability is population differentiation, which can induce coancestry among subpopulation members. Forensic assessments that ignore coancestry typically overstate the strength of evidence against the suspect. Theory has been developed to account for coancestry; assumptions include a steady-state population and a mutation model in which the allelic state after a mutation event is independent of the prior state. Under these assumptions, the joint allelic probabilities within a subpopulation may be approximated by the moments of a Dirichlet distribution. We investigate the adequacy of this approximation for profiled loci that mutate according to a generalized stepwise model. Simulations suggest that the Dirichlet theory can still overstate the evidence against a suspect with a common microsatellite genotype. However, Dirichlet-based estimators were less biased than the product-rule estimator, which ignores coancestry.


2019 ◽  
Vol 108 (2) ◽  
pp. e115-e117
Author(s):  
Kelly Brown ◽  
Robert Homer ◽  
Marina Baine ◽  
Justin D. Blasberg

1999 ◽  
Vol 65 (1) ◽  
pp. 208-219 ◽  
Author(s):  
Anna Pérez-Lezaun ◽  
Francesc Calafell ◽  
David Comas ◽  
Eva Mateu ◽  
Elena Bosch ◽  
...  

Gene ◽  
2008 ◽  
Vol 410 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Edit Kassai-Jáger ◽  
Csaba Ortutay ◽  
Gábor Tóth ◽  
Tibor Vellai ◽  
Zoltán Gáspári

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