Profiling variable-number tandem repeat variation across populations using repeat-pangenome graphs

Variable Number ◽

Population Diversity ◽

Protein Coding ◽

Short Reads ◽

Repeat Structure ◽

Tandem Repeat Sequences ◽

Continental Population

AbstractVariable number tandem repeat sequences (VNTR) are composed of consecutive repeats of short segments of DNA with hypervariable repeat count and composition. They include protein coding sequences and associations with clinical disorders. It has been difficult to incorporate VNTR analysis in disease studies that use short-read sequencing because the traditional approach of mapping to the human reference is less effective for repetitive and divergent sequences. We solve VNTR mapping for short reads with a repeat-pangenome graph (RPGG), a data structure that encodes both the population diversity and repeat structure of VNTR loci from multiple haplotype-resolved assemblies. We developed software to build a RPGG, and use the RPGG to estimate VNTR composition with short reads. We used this to discover VNTRs with length stratified by continental population, and novel expression quantitative trait loci, indicating that RPGG analysis of VNTRs will be critical for future studies of diversity and disease.

Profiling variable-number tandem repeat variation across populations using repeat-pangenome graphs

Nature Communications ◽

10.1038/s41467-021-24378-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Tsung-Yu Lu ◽

Katherine M. Munson ◽

Alexandra P. Lewis ◽

Qihui Zhu ◽

Luke J. Tallon ◽

...

Keyword(s):

Tandem Repeats ◽

Traditional Approach ◽

Variable Number ◽

Population Diversity ◽

Protein Coding ◽

Short Reads ◽

Repeat Structure ◽

Continental Population ◽

Develop Software

AbstractVariable number tandem repeats (VNTRs) are composed of consecutive repetitive DNA with hypervariable repeat count and composition. They include protein coding sequences and associations with clinical disorders. It has been difficult to incorporate VNTR analysis in disease studies that use short-read sequencing because the traditional approach of mapping to the human reference is less effective for repetitive and divergent sequences. In this work, we solve VNTR mapping for short reads with a repeat-pangenome graph (RPGG), a data structure that encodes both the population diversity and repeat structure of VNTR loci from multiple haplotype-resolved assemblies. We develop software to build a RPGG, and use the RPGG to estimate VNTR composition with short reads. We use this to discover VNTRs with length stratified by continental population, and expression quantitative trait loci, indicating that RPGG analysis of VNTRs will be critical for future studies of diversity and disease.

Evolutionary clues from comparative analysis of Mycobacterium tuberculosis variable-number tandem repeat sequences within genetic families☆

Infection Genetics and Evolution ◽

10.1016/j.meegid.2006.09.006 ◽

2007 ◽

Vol 7 (2) ◽

pp. 239-246 ◽

Cited By ~ 4

Author(s):

Nicola Thorne ◽

Anthony Underwood ◽

Saheer Gharbia ◽

Cath Arnold

Keyword(s):

Mycobacterium Tuberculosis ◽

Comparative Analysis ◽

Tandem Repeat ◽

Variable Number ◽

Repeat Sequences ◽

Tandem Repeat Sequences

Reply to "Evaluation of Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeat Genotyping as Performed in Laboratories in Canada, France, and the United States"

10.1128/jcm.00233-12 ◽

2012 ◽

Vol 50 (5) ◽

pp. 1832-1832

Author(s):

J. L. de Beer ◽

D. van Soolingen

Keyword(s):

United States ◽

Tandem Repeat ◽

The United States ◽

Variable Number

Comparison of Multilocus Variable-Number Tandem-Repeat Analysis and Whole-Genome Sequencing for Investigation of Clostridium difficile Transmission

10.1128/jcm.01095-13 ◽

2013 ◽

Vol 51 (12) ◽

pp. 4141-4149 ◽

Cited By ~ 48

Author(s):

D. W. Eyre ◽

W. N. Fawley ◽

E. L. Best ◽

D. Griffiths ◽

N. E. Stoesser ◽

...

Keyword(s):

Clostridium Difficile ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Tandem Repeat ◽

Variable Number ◽

Whole Genome ◽

Repeat Analysis

Evaluating the Use of Multilocus Variable Number Tandem Repeat Analysis of Shiga Toxin-Producing Escherichia coli O157 as a Routine Public Health Tool in England

PLoS ONE ◽

10.1371/journal.pone.0085901 ◽

2014 ◽

Vol 9 (1) ◽

pp. e85901 ◽

Cited By ~ 17

Author(s):

Lisa Byrne ◽

Richard Elson ◽

Timothy J. Dallman ◽

Neil Perry ◽

Philip Ashton ◽

...

Keyword(s):

Public Health ◽

Escherichia Coli ◽

Tandem Repeat ◽

Shiga Toxin ◽

Variable Number ◽

Escherichia Coli O157 ◽

Repeat Analysis

Multilocus Variable-Number Tandem-Repeat Analysis, Pulsed-Field Gel Electrophoresis, and Antimicrobial Susceptibility Patterns in Discrimination of Sporadic and Outbreak-Related Strains of Yersinia enterocolitica

BMC Microbiology ◽

10.1186/1471-2180-11-42 ◽

2011 ◽

Vol 11 (1) ◽

pp. 42 ◽

Cited By ~ 30

Author(s):

Leila M Sihvonen ◽

Susanna Toivonen ◽

Kaisa Haukka ◽

Markku Kuusi ◽

Mikael Skurnik ◽

...

Keyword(s):

Yersinia Enterocolitica ◽

Tandem Repeat ◽

Antimicrobial Susceptibility ◽

Gel Electrophoresis ◽

Variable Number ◽

Pulsed Field Gel Electrophoresis ◽

Pulsed Field ◽

Repeat Analysis ◽

Susceptibility Patterns

Evaluation of Multiple-Locus Variable-Number Tandem-Repeat Analysis for Typing a Polyclonal Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Population in an Area Where Such Infections Are Endemic

10.1128/jcm.02220-09 ◽

2010 ◽

Vol 48 (8) ◽

pp. 2991-2994 ◽

Cited By ~ 8

Author(s):

B. Rivero-Perez ◽

E. Perez-Roth ◽

S. Mendez-Alvarez

Keyword(s):

Staphylococcus Aureus ◽

Tandem Repeat ◽

Methicillin Resistant Staphylococcus Aureus ◽

Variable Number ◽

Methicillin Resistant ◽

Multiple Locus ◽

Repeat Analysis ◽

Hospital Acquired

Mycobacterium tuberculosis in Ontario, Canada: Insights from IS6110 Restriction Fragment Length Polymorphism and Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeat Genotyping

10.1128/jcm.01946-08 ◽

2009 ◽

Vol 47 (8) ◽

pp. 2651-2654 ◽

Cited By ~ 6

Author(s):

D. C. Alexander ◽

J. L. Guthrie ◽

D. Pyskir ◽

A. Maki ◽

N. Kurepina ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Restriction Fragment Length Polymorphism ◽

Restriction Fragment ◽

Length Polymorphism ◽

Tandem Repeat ◽

Fragment Length ◽

Fragment Length Polymorphism ◽

Variable Number ◽

Restriction Fragment Length

Multiple-Locus Variable-Number Tandem Repeat Analysis of Dutch Bordetella pertussis Strains Reveals Rapid Genetic Changes with Clonal Expansion during the Late 1990s

Journal of Bacteriology ◽

10.1128/jb.186.16.5496-5505.2004 ◽

2004 ◽

Vol 186 (16) ◽

pp. 5496-5505 ◽

Cited By ~ 99

Author(s):

Leo M. Schouls ◽

Han G. J. van der Heide ◽

Luc Vauterin ◽

Paul Vauterin ◽

Frits R. Mooi

Keyword(s):

The Netherlands ◽

Tandem Repeat ◽

Bordetella Pertussis ◽

Minimum Spanning Tree ◽

Whooping Cough ◽

Clonal Expansion ◽

Variable Number ◽

Multiple Locus ◽

Repeat Analysis

ABSTRACT Bordetella pertussis, the causative agent of whooping cough, has remained endemic in The Netherlands despite extensive nationwide vaccination since 1953. In the 1990s, several epidemic periods have resulted in many cases of pertussis. We have proposed that strain variation has played a major role in the upsurges of this disease in The Netherlands. Therefore, molecular characterization of strains is important in identifying the causes of pertussis epidemiology. For this reason, we have developed a multiple-locus variable-number tandem repeat analysis (MLVA) typing system for B. pertussis. By combining the MLVA profile with the allelic profile based on multiple-antigen sequence typing, we were able to further differentiate strains. The relationships between the various genotypes were visualized by constructing a minimum spanning tree. MLVA of Dutch strains of B. pertussis revealed that the genotypes of the strains isolated in the prevaccination period were diverse and clearly distinct from the strains isolated in the 1990s. Furthermore, there was a decrease in diversity in the strains from the late 1990s, with a remarkable clonal expansion that coincided with the epidemic periods. Using this genotyping, we have been able to show that B. pertussis is much more dynamic than expected.