Global Alert and Response (GAR)

Abstracts summarizing recent research overseen by the WHO Advisory Committee on Variola Virus Research - 2004


Inferring the Phylogeny of Variola from Genomic SNPs Analysis

Yu Li2, Shea Gardner1, Walsh, Matthew2, Victoria Olson2, Tom Slezak1, Beth Vitalis1, Scott Sammons2, Mike Frace2, Joe Esposito2, Russell Regnery2 and Inger Damon2.

1Homeland Security Informatics Group, Computations Directorate Lawrence Livermore National Laboratory;

2 Poxvirus activity, NCID/DVRD, Centers for Diseases Control and Preventions, Atlanta, United States of America

Please direct all queries to the authors at the addresses given.

Single nucleotide polymorphisms (SNPs) afford a detailed genetic analysis of species diversity, and have recently been used to infer phylogeny. We describe a novel method to compare SNPs from closely related variola and/or camelpox genome sequences. Using a concatenated figure matrix, the method permits objective analysis of SNPs, and removes uncertainty induced by gaps of deletion or insertion. It also allows manual inspection of the dataset.

SNPs were defined as 12 nucleotides of identical sequence flanking a polymorphic position. 960 SNPs were generated from comparison of 32 variola genome sequences. A variety of analytic approaches were used; the phylogenetic tree derived from SNPs analysis is consistent with the trees derived from genomic ePCR/RFLP analysis or selected sequence based analysis, indicating the selected SNPs were representative of genetic diversity of variola genome.

Analysis was also completed using camelpox as an outlier. Cluster analysis of the SNPs concatenated figure matrixs indicates that: 1) variola major and variola alastrim minor diverged from a common variola ancestor and evolved independently; 2) West Africa variola strains from the collection have common ancestry with Brazilian alastrim minor strains. Reduction of the dataset leads to an interesting speculation relating East Asia variola major strains to Brazilian alastrim minor and West Africa variola strains.

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