Reviews & Analysis

A common inversion segregating in human populations reminds us of the complex interactions between different levels of genomic diversity, from single nucleotide variants to large-scale genomic rearrangements. These rearrangements are of special interest when they bear the mark of natural selection.

Most cases of Rett syndrome are caused by mutations in MECP2. Transcriptional profiling analyses of the brains of individuals with Rett syndrome have not provided consistent data about genes that are silenced by MECP2. A new study finds loss of imprinting of a maternally imprinted gene, DLX5, both in Mecp2-null mice and in some lymphoblastoid cell lines obtained from individuals with Rett syndrome.

The XY chromosome pair in mammalian males is sequestered into a transcriptionally dormant chromatin domain before the first meiotic division. New work shows that all chromosomes can suffer the same fate if they don't pair during meiosis, and that this may be part of a surveillance mechanism to protect against aneuploid gametes.

Epistasis is a phenomenon whereby the effects of a given gene on a biological trait are masked or enhanced by one or more other genes. A new study documents epistasis among 890 metabolic genes in yeast, providing one of the largest data sets of its kind in any model organism.

Modeling of human cancer in genetically engineered mice and genome-wide measurements of mRNA expression have now been combined to accelerate the search for new molecularly targeted therapies against cancer. Looking forward, we propose a community-wide systematic effort to model and characterize an array of different cancer-related aberrant signaling pathways in several mouse models of cancer.

Negative trade-offs are thought to be a pervasive phenomenon and to inhibit evolution at all levels. New evidence shows that at the molecular level, there may be no trade-offs preventing the emergence of an enzyme with multiple functions.