NEW YORK (GenomeWeb News) – In the early, online version of Genome Research, America researchers outline the strategy they used to look at the gene expression consequences of endogenous retrovirus transposon insertion in mice from six genetic backgrounds.
Using a transposon junction assay that relied on PCR combined with Roche 454 sequencing, the team mapped genomic insertion sites for a range of ERVs, particularly those from transposable element families expected to show polymorphic effects in the strains. They then looked at where these ERVs occurred with respect to coding and non-coding sequences and assessed their effects on the mouse transcriptome.
"We observed very, very strong disruption of certain mouse genes by ERVs acting at a long genomic distance, and the resulting expression differences — up to almost 50-fold changes — can have major biological consequences that distinguish between the strains," Ohio State University researcher David Symer, the study's senior author, said in a statement.
Two independent teams reporting in Nature Genetics used exome sequencing to identify mutations contributing to developmental conditions called Nicolaides-Baraitser syndrome and Baraitser-Winter syndrome, respectively.
An international group led by researchers in Belgium and the Netherlands found dominant, de novo mutations in the chromatin remodeling complex gene SMARCA2 in eight of the 10 exomes they sequenced for individuals with NBS — results that they verified by Sanger sequencing. Non-synonymous mutations in SMARCA2, which codes for a SWI/SNF complex component, turned up in 28 more of the 34 individuals with NBS who were screened for subsequent stages of the study. Because the mutations fell within a gene region coding for a highly conserved, ATP-interacting portion of the resulting enzyme, the study authors argued that "[t]hese alterations likely do not impair SWI/SNF complex assembly but may be associated with disrupted ATPase activity."
Meanwhile, researchers from the University of Washington, the University Hospital of Wales, and elsewhere sequenced the exomes of three children with Baraitser-Winter syndrome and their unaffected parents, identifying de novo missense mutations actin-related genes in each of the children. One child with Baraitser-Winter syndrome had alterations in the gene ACTB, they report, while two others carried ACTG1 mutations. When they did Sanger sequencing of the two genes in 15 more individuals with Baraitser-Winter syndrome, researchers found mutations to one of the two genes in all of the cases. Moreover, eight of the affected individuals had changes to the same ACTB codon, while three had mutations affecting a specific residue of the ACTG1 gene product.
A Proceedings of the National Academy of Sciences study by a University of California at Irvine-led group that's set to appear online this week looks at the co-evolution that can occur between the marine cyanobacterium Synechococcus and a lytic virus RIM8 from the Myoviridae family.
The team grew Synechococcus in the presence or absence of the RIM8 virus over six months in a chemostat continuous culture system. Their analyses uncovered a range of phenotypes consistent with antagonistic co-evolution in both Synechococcus and RIM8 during the course of the experiments. Through genomic and other analyses, the study authors also explored the genetic elements mediating these interactions.
"Our results indicate that rapid co-evolution may contribute to the generation and maintenance of Synechococcus and virus diversity," UC Irvine ecology and evolutionary biology researcher Jennifer Martiny, and colleagues wrote, "and thereby influence viral-mediated mortality of these key marine bacteria."
An epigenetic blockade of gene expression caused by elevated histone deacetylase 2 levels contributes to forgetfulness and other forms of cognitive decline seen during Alzheimer's disease, according to a study online in Nature.
In their mouse model of Alzheimer's disease and neurodegeneration, Massachusetts researchers found that when levels of histone deacetylase rise in certain parts of the brain, it ramps up the enzyme's removal of acetyl groups from histones at learning and memory related genes, leading to muted expression of these genes — a pattern that appears to be consistent with the enhanced levels of HDAC2 found in post-mortem brain samples from Alzheimer's patients. On the other hand, by blocking the enzyme's actively with short-hairpin RNAs that target HDAC2, the investigators were able to loosen the brakes on gene expression and improve cognitive performance in mouse models.
"The neurons that are still alive are essentially zombies: they're not really functioning properly because of the epigenetic blockade," the study's corresponding author Li-Huei Tsai from the Massachusetts Institute of Technology, said in a statement. "What we're showing is that, if we can get some of those neurons to wake up, we can get cognitive function to recover to a certain extent."
Genomics In The Journals is a weekly feature pointing readers to select, recently published articles involving genomics and related research.