sSNPs and nsSNPs
Chen R, Davydov EV, Sirota M, et al. (2010). Non-synonymous and synonymous coding SNPs show similar likelihood and effect size of human disease association. PLoS Biology. 5(10): e13574.
Rong Chen and his colleagues surveyed 21,429 disease-SNP associations curated from 2,113 publications to investigate whether synonymous coding SNPs and other non-coding SNPs might be equally responsible for high disease odds ratios as non--synonymous coding SNPs seem to be. The authors found that both nsSNPs and sSNPs share similar likelihood and effect size for disease association. "Our results suggest that sSNPs are just as likely to be involved in disease mechanisms, so we recommend that sSNPs discovered from GWAS should also be examined with functional studies," Chen et al. write.
Elachouri G, Vidoni S, Zanna C, et al. (2010). OPA1 links human mitochondrial genome maintenance to mtDNA replication and distribution. Genome Research. Epub: doi 10.1101.
Using siRNAs specific to alternatively spliced exons in OPA1, Ghizlane Elachouri et al. found that silencing OPA1 variants, including exon4b, leads to mtDNA depletion — secondary to inhibition of mtDNA replication — and to marked alteration of mtDNA distribution in nucleoids spread throughout the mitochondrial network. In their paper, the team describes a synthetic model in which a peptide, generated by the cleavage of OPA1-exon4b isoform, could play a role in nucleoid attachment to the inner mitochondrial membrane, thereby implicating OPA1 as a key player in mitochondrial genome maintenance.
Kong A, Thorleifsson G, Gudbjartsson DF, et al. (2010). Fine-scale recombination rate differences between sexes, populations, and individuals. Nature. Epub: doi 10.1038.
The authors used genome-wide SNP data from 15,257 parent-offspring pairs to build the first recombination maps based on observed recombinations with a resolution that is effectively down to 10 kilobases. Through this approach, the team discovered novel associations among individuals' recombination characteristics and PRDM9 gene variants, and identified new recombination hotspots. According to the authors, comparisons of "two [linkage disequilibrium]-based maps inferred from data of HapMap populations ... reveal population differences previously masked by noise and map differences at regions previously described as targets of natural selection."
Derdowski A, Sindi SS, Klaips CL, et al. (2010). A size threshold limits prion transmission and establishes phenotypic diversity. Science. Epub: doi 10.1126.
Using the yeast prion Sup35, Aaron Derdowski and his colleagues set out to study how amyloid formation in vitro interacts with cells to form transmissible phenotypes. They demonstrate that the protein's conformation determines the size distribution of aggregates through its interactions with a molecular chaperone. Their paper describes how shifts in this range result in "variations in aggregate abundance among cells because of a size threshold for transmission, and this heterogeneity, along with aggregate growth and fragmentation, induced age-dependent fluctuations in phenotype. Thus, prion conformations may specify phenotypes as population averages in a dynamic system."