Evaluation of customised lineage-specific sets of MIRU-VNTR loci for genotyping Mycobacterium tuberculosis complex isolates in Ghana

Adwoa Asante-Poku; Michael Selasi Nyaho; Sonia Borrell; Iñaki Comas; Sebastien Gagneux; Dorothy Yeboah-Manu

doi:10.1371/journal.pone.0092675

Evaluation of customised lineage-specific sets of MIRU-VNTR loci for genotyping Mycobacterium tuberculosis complex isolates in Ghana

PLoS One. 2014 Mar 25;9(3):e92675. doi: 10.1371/journal.pone.0092675. eCollection 2014.

Authors

Adwoa Asante-Poku¹, Michael Selasi Nyaho², Sonia Borrell³, Iñaki Comas⁴, Sebastien Gagneux³, Dorothy Yeboah-Manu⁵

Affiliations

¹ Bacteriology Department, Noguchi Memorial institute For Medical Research, University of Ghana, Legon, Ghana; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
² Bacteriology Department, Noguchi Memorial institute For Medical Research, University of Ghana, Legon, Ghana; Biochemistry Department, University of Ghana, Legon, Ghana.
³ Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
⁴ Genomics and Health Unit, Centre for Public Health Research, Valencia, Spain; CIBER (Centros de Investigación Biomédica en Red) in Epidemiology and Public Health, Madrid, Spain.
⁵ Bacteriology Department, Noguchi Memorial institute For Medical Research, University of Ghana, Legon, Ghana.

Abstract

Background: Different combinations of variable number of tandem repeat (VNTR) loci have been proposed for genotyping Mycobacterium tuberculosis complex (MTBC). Existing VNTR schemes show different discriminatory capacity among the six human MTBC lineages. Here, we evaluated the discriminatory power of a "customized MIRU12" loci format proposed previously by Comas et al. based on the standard 24 loci defined by Supply et al. for VNTR-typing of MTBC in Ghana.

Method: One hundred and fifty-eight MTBC isolates classified into Lineage 4 and Lineage 5 were used to compare a customized lineage-specific panel of 12 MIRU-VNTR loci ("customized MIRU-12") to the standard MIRU-15 genotyping scheme. The resolution power of each typing method was determined based on the Hunter-Gaston- Discriminatory Index (HGDI). A minimal set of customized MIRU-VNTR loci for typing Lineages 4 (Euro-American) and 5 (M. africanum West African 1) strains from Ghana was defined based on the cumulative HGDI.

Results and conclusion: Among the 106 Lineage 4 strains, the customized MIRU-12 identified a total of 104 distinct genotypes consisting of 2 clusters of 2 isolates each (clustering rate 1.8%), and 102 unique strains while standard MIRU-15 yielded a total of 105 different genotypes, including 1 cluster of 2 isolates (clustering rate: 0.9%) and 104 singletons. Among, 52 Lineage 5 isolates, customized MIRU-12 genotyping defined 51 patterns with 1 cluster of 2 isolates (clustering rate: 0.9%) and 50 unique strains whereas MIRU-15 classified all 52 strains as unique. Cumulative HGDI values for customized MIRU-12 for Lineages 4 and 5 were 0.98 respectively whilst that of standard MIRU-15 was 0.99. A union of loci from the customised MIRU-12 and standard MIRU-15 revealed a set of customized eight highly discriminatory loci: 4052, 2163B, 40, 4165, 2165, 10,16 and 26 with a cumulative HGDI of 0.99 for genotyping Lineage 4 and 5 strains from Ghana.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Genotype*
Ghana / epidemiology
Humans
Male
Minisatellite Repeats*
Mycobacterium tuberculosis / genetics*
Mycobacterium tuberculosis / isolation & purification*
Tuberculosis / epidemiology
Tuberculosis / genetics*

Grants and funding

This study was supported financially by the UNICEF/UNDP/World Bank/WHO special program for research and training in Tropical Diseases for DY-M and the Leverhulme-Royal Society Africa (DY-M and SG) and NTP Ghana. Funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.