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hdl:10101/npre.2007.743.2
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Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin

Henry L. Niman1, Magdi D. Saad2, Jeffery Tjaden2, Kenneth C. Earhart2, Marshall R. Monteville2, Mona M. Aly3, Moustafa M. Mansour2, Nasr El-Sayed 4, Ahmed E. Nayel4, Ahmed S. Abdelghani4, Hala M. Esmat2, Emad M. Labib2, Ehab A. Ayoub2, Abdelattar Arafa3, Gregory A. Raczniak5, Mensah Agyen-Frempong 6, William K. Ampofo7, & Bruce R. Boynton2

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  1. Recombinomics, Inc
  2. U.S. Naval Medical Research Unit 3 (NAMRU-3)
  3. Central Laboratory for Veterinary Quality Control, Giza
  4. Ministry of Health, Arabic Republic of Egypt
  5. NAMRU-3 Ghana Detachment
  6. Ghana Veterinary Services
  7. Noguchi Memorial Institute for Medical Research
Document Type:
Manuscript
Date:
Received 10 September 2007 09:26 UTC; Posted 12 September 2007
Subjects:
Biotechnology, Chemistry, Evolution and Ecology, Genetics, Immunology, Microbiology, Bioinformatics
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Abstract:

The rapid evolution of the H5N1 serotype of avian influenza has been explained by a mechanism involving the selection of single nucleotide polymorphisms generated by copy errors. The recent emergence of H5N1 Clade 2.2 in fifty countries, offered a unique opportunity to view the acquisition of new polymorphism in these evolving genomes. We analyzed the H5N1 hemagglutinin gene from a fatal human case from Nigeria in 2007. The newly emerged polymorphisms were present in diverse H5N1 isolates from the previous year. The aggregation of these polymorphisms from clade 2.2 sub-clades was not supported by recent random mutations, and was most easily explained by recombination between closely related sequences.

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Henry Niman on 15 January 2008 11:03 UTC

Sequences twelve 2007 chicken isolates from Nigeria were just made public. These sequences fully support the aggregation of single nucleotide polymorphisms previously described in the human influenza HA sequence, A/Nigeria/6/07. Four of the chicken isolates were virtually identical to the human influenza HA sequence (see list below), while six more were closely related. Two of the isolates were closely related to a subset of 2006 isolates from Nigeria.

The “Aggregation” paper described 14 polymorphisms that were shared with other clade 2.2 isolates. All 14 of these polymorphisms were present in the newly released chicken influenza sequences from Nigeria. Thirteen of the fourteen were in the four sequences virtually identical to the human influenza sequence. The only polymorphism, C1480T, not in the four closely related sequences was present in the two isolates related to the subset of 2006 isolates. In addition, seven of the fourteen polymorphisms (G295A, A433G, G643A, G781A, C981T, G1685A, A1708G) were present in the ten most closely related sequences.

These data support the previously described aggregation of single nucleotide polymorphisms from diverse clade 2.2 sub-clades.

This aggregation is most easily explained by homologous recombination in H5N1 influenza A.

Virtually identical HA sequences

EU148428 A/chicken/Nigeria/1071-23/2007
EU148372 A/chicken/Nigeria/1071-4/2007
EU148380 A/chicken/Nigeria/1071-5/2007
EU148396 A/chicken/Nigeria/1071-9/2007

Closely related HA sequences

EU148356 A/chicken/Nigeria/1071-1/2007
EU148404 A/chicken/Nigeria/1071-10/2007
EU148412 A/chicken/Nigeria/1071-15/2007
EU148420 A/chicken/Nigeria/1071-22/2007
EU148436 A/chicken/Nigeria/1071-29/2007
EU148444 A/chicken/Nigeria/1071-30/2007

More distantly related HA sequences

EU148364 A/chicken/Nigeria/1071-3/2007
EU148388 A/chicken/Nigeria/1071-7/2007

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This document is licensed to the public under the Creative Commons Attribution 2.5 License
How to cite this document:

Niman, Henry, Saad, Magdi, Tjaden, Jeffery, Earhart, Kenneth, Monteville, Marshall, Aly, Mona, Mansour, Moustafa, El-Sayed , Nasr, Nayel, Ahmed, Abdelghani, Ahmed, Esmat, Hala, Labib, Emad, Ayoub, Ehab, Arafa, Abdelattar, Raczniak, Gregory, Agyen-Frempong , Mensah, Ampofo, William, and Boynton, Bruce. Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2007.743.2> (2007)

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v1 Posted 16 August 2007

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