D225G/N H1N1 Linkage by Recombination in Australia US China



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H1N1 Consulting Paradigm Shift Viral Evolution Intervention Monitoring Vaccine Screening Vaccine Development Expression Profiling Drug Discovery Custom Therapies Patents	Audio:Jan6 Jan13 Jan16 Jan21 twitter Live feed of underlying pandemic map data here Commentary D225G/N H1N1 Linkage by Recombination in Australia US China Recombinomics Commentary 23:55 January 31, 2010 JCVI has released a series of full sequences at Genbank. Although most were from California, three sequences were from Australia, including A/Australia/6/2009. This sequence begins with two polymorphisms that are found in Australian sequences with D225G or D225N. The third polymorphism is Y233H, which is in the Duke death cluster in North Carolina, which has D225G and D225N. The fourth polymorphism is in the China cluster in Zhejian province, which also has D225G. Thus, the Australia HA sequence has polymorphisms which link together three distinct sub-clades with D225G and D225N, providing compelling evidence for movement of these polymorphisms by homologous recombination. Although each of these sub-clades contains D225G, D225N, or both, prior to the release of the Australian sequence the sub-clades were unlinked, other than the common changes at position 225. The Australian sub-clade had two polymorphisms that were found in Australian sequences, but the sequences with the position 225 diverged, and one series had A/VICTORIA/2125/2009 with D225N and A/SYDNEY/2503/2009 with D225G, while the other branch had SYDNEY/2501/2009 with D225N. The Australian/6 sequence has both of these polymorphism (A208G and T519C) – see list here and here. The third polymorphism in Australia 6 is T739C, which codes for Y233H. This polymorphism is found in isolates from the cluster of patients at Duke Medical Center who also had H274Y. In this group there were two sequences with D225G and one with D225N (see list here). The fourth polymorphism is in the cluster of sequences from Zhejian Province in China. All three sequences have D225G (see list here). Thus, the one sequence in Australian has polymorphisms found in three distinct sub-lades with clusters of sequences with D225G and/or D225N providing a mechanism of recombination for movement of D225G and D225N from one sub-clade to another. Frequent jumping from one genetic background has been described in the above sub-clades as well as the sub-clade found in Ukraine, Russia, and Norway. Interestingly, the CDC just released another sequence (at GISAID) from North Carolina with D225G (A/North Carolina/53/2009) which is in the Ukraine sub-clade. Thus, these sub-clades with D225G and D225N are becoming increasingly widespread, which facilitates further jumps, as was seen for H274Y in H1N1 seasonal flu and is being repeated in H1N1 pandemic flu. The use of homologous recombination allows the polymorphisms to jump from one genetic background to the next, facilitating rapid evolution to escape immune responses generated by prior infections or vaccinations. Media Links Recombinomics Presentations Recombinomics Publications Recombinomics Paper at Nature Precedings

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