Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades

Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997 1,2. The number of confirmed human cases now exceeds 300 and the associated Case Fatality Rate exceeds 60% 3. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases 4-7. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift 8. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, Kuwait, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. The recombination role is further supported by the high fidelity replication in swine influenza 9 and aggregation of single nucleotide polymorphisms in H5N1 clade 2.2 hemagglutinin 10

Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades

Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997. The number of confirmed human cases now exceeds 300, and the associated Case Fatality Rate exceeds 60%. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by clade 2.2 isolates in Egypt and Germany

Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin

The evolution of H5N1 has attracted significant interest 1-4 due to linkages with avian 5,6 and human infections 7,8. The basic tenets of influenza genetics 9 attribute genetic drift to replication errors caused by a polymerase complex that lacks a proof reading function. However, recent analysis 10 of swine influenza genes identifies regions copied with absolute fidelity for more than 25 years. In addition, polymorphism tracing of clade 2.2 H5N1 single nucleotide polymorphisms identify concurrent acquisition 11 of the same polymorphism onto multiple genetic backgrounds in widely dispersed geographical locations. Here we show the aggregation of regional clade 2.2 polymorphisms from Germany, Egypt, and sub-Sahara Africa onto a human Nigerian H5N1 hemagglutinin (HA), implicating recombination in the dispersal and aggregation of single nucleotide polymorphisms from closely related genomes

Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin

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

An ice-rich flow origin for the banded terrain in the Hellas basin, Mars

The interior of Hellas Basin displays a complex landscape and a variety of geomorphological domains. One of these domains, the enigmatic banded terrain covers much of the northwestern part of the basin. We use high-resolution (Context Camera and High-Resolution Imaging Science Experiment) Digital Terrain Models to show that most of the complex viscous flowing behavior exhibited by the banded terrain is controlled by topography and flow-like interactions between neighboring banded terrain. Furthermore, the interior of the basin hosts several landforms suggestive of the presence of near-surface ice, which include polygonal patterns with elongated pits, scalloped depressions, isolated mounds, and collapse structures. We suggest that thermal contraction cracking and sublimation of near-surface ice are responsible for the formation and the development of most of the ice-related landforms documented in Hellas. The relatively pristine form, lack of superposed craters, and strong association with the banded terrain, suggest an Amazonian (<3 Ga) age of formation for these landforms. Finally, relatively high surface pressures (above the triple point of water) expected in Hellas and summertime temperatures often exceeding the melting point of water ice suggest that the basin may have recorded relatively “temperate” climatic conditions compared to other places on Mars. Therefore, the potentially ice-rich banded terrain may have deformed with lower viscosity and stresses compared to other locations on Mars, which may account for its unique morphology

Stakeholder views on secondary findings in whole-genome and whole-exome sequencing:a systematic review of quantitative and qualitative studies

Purpose: As whole-exome and whole-genome sequencing (WES/WGS) move into routine clinical practice, it is timely to review data that might inform the debate around secondary findings (SF) and the development of policies that maximize participant benefit. Methods: We systematically searched for qualitative and quantitative studies that explored stakeholder views on SF in WES/WGS. Framework analysis was undertaken to identify major themes. Results: 44 articles reporting the views of 11,566 stakeholders were included. Stakeholders were broadly supportive of returning ‘actionable’ findings, but definitions of actionability varied. Stakeholder views on SF disclosure exist along a spectrum: potential WES/WGS recipients’ views were largely influenced by a sense of rights, while views of genomics professionals were informed by a sense of professional responsibility. Experience of genetic illness and testing resulted in greater caution about SF, suggesting that truly informed decisions require an understanding of the implications and limitations of WES/WGS and possible findings. Conclusion: This review suggests that bidirectional interaction during consent might best facilitate informed decision-making about SF, and that dynamic forms of consent, allowing for changing preferences, should be considered. Research exploring views from wider perspectives and from recipients who have received SF is critical if evidence-based policies are to be achieved.</p