http://precedings.nature.com/tags/Genetics Recently posted documents tagged with 'Genetics' Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/1799/version/1 Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available. http://precedings.nature.com/documents/1799/version/1 Tue, 15 Apr 2008 12:55:56 UTC Intra- and inter-individual genetic differences in gene expression hdl:10101/npre.2008.1799.1 2008-04-15 Mark J. Cowley Nature Precedings 2008-04-15T12:55:56Z Manuscript Genetics & Genomics Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/743/version/2 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. http://precedings.nature.com/documents/743/version/2 Wed, 12 Sep 2007 11:04:26 UTC Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin hdl:10101/npre.2007.743.2 2009-03-04 Henry L. Niman Nature Precedings 2007-09-12T11:04:26Z Manuscript Genetics & Genomics Evolutionary Biology http://creativecommons.org/licenses/by/2.5/ http://precedings.nature.com/documents/459/version/3 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. http://precedings.nature.com/documents/459/version/3 Wed, 12 Sep 2007 10:27:59 UTC Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades hdl:10101/npre.2007.459.3 2007-09-12 Henry L. Niman Nature Precedings 2007-09-12T10:27:59Z Manuscript Biotechnology Chemistry Ecology Genetics & Genomics Immunology Microbiology Bioinformatics http://creativecommons.org/licenses/by/2.5/ http://precedings.nature.com/documents/743/version/1 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. http://precedings.nature.com/documents/743/version/1 Thu, 16 Aug 2007 15:53:42 UTC Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin hdl:10101/npre.2007.743.1 2007-08-16 Henry L. Niman Nature Precedings 2007-08-16T15:53:42Z Manuscript Biotechnology Ecology Genetics & Genomics Immunology Microbiology Bioinformatics http://creativecommons.org/licenses/by/2.5/ http://precedings.nature.com/documents/459/version/2 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. http://precedings.nature.com/documents/459/version/2 Mon, 23 Jul 2007 13:45:43 UTC Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades hdl:10101/npre.2007.459.2 2007-07-23 Henry L. Niman Nature Precedings 2007-07-23T13:45:43Z Manuscript Biotechnology Ecology Genetics & Genomics Microbiology Bioinformatics http://creativecommons.org/licenses/by/2.5/ http://precedings.nature.com/documents/459/version/1 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, 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. http://precedings.nature.com/documents/459/version/1 Mon, 16 Jul 2007 05:09:59 UTC Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades hdl:10101/npre.2007.459.1 2007-07-16 Henry L. Niman Nature Precedings 2007-07-16T05:09:59Z Manuscript Biotechnology Ecology Genetics & Genomics Microbiology Bioinformatics http://creativecommons.org/licenses/by/2.5/ http://precedings.nature.com/documents/385/version/1 The looming influenza pandemic has focused attention1-4 on the rapid evolution of H5N1 and other human and avian serotypes. The basic tenets of influenza genetics5 define gradual changes as drifts caused by point mutations created by a polymerase that lacks a proof reading function. More abrupt changes have been linked to reassortment, which shuffles the eight sub-genomic segments of the influenza genome in dually infected host. The complex evolution of these viruses has created a challenge in vaccine development. Swine influenza isolates from 2003 and 2004 have been identified6 that have acquired a human influenza gene, PB1. My analysis of the eight gene segments found large portions of two genes, PB2 and PA, which were identical matches with 1977 swine isolates7,8. Additional regions were exact matches with 1998 and 2002 isolates,9,10 demonstrating homologous recombination between earlier genomes. The absolute fidelity discounts the role of point mutations in gene drift. Moreover the human PB1 gene represented a reservoir for acquisition of polymorphisms in human seasonal flu. These observations challenge the basic tenets of influenza genetics and provide a method for predicting the changes in seasonal and pandemic influenza, as well as other rapidly evolving genomes. http://precedings.nature.com/documents/385/version/1 Tue, 10 Jul 2007 13:59:11 UTC Swine Influenza A Evolution via Recombination – Genetic Drift Reservoir hdl:10101/npre.2007.385.1 2009-01-09 Henry L. Niman Nature Precedings 2007-07-10T13:59:11Z Manuscript Ecology Genetics & Genomics http://creativecommons.org/licenses/by/2.5/