News & Views in 2005

Maternal hypertension in pregnancy is a genetically complex condition originating in the placenta. Because of imprinting, only the maternal copy of the gene encoding STOX1 is expressed in invasive placental extravillous trophoblasts. Therefore, maternally inherited missense mutations affecting this putative DNA-binding protein predispose to preeclampsia, possibly by interfering with differentiation of the trophoblast cells.

A microarray-based study of the nematode Caenorhabditis elegans offers a first glimpse of the effect of mutation accumulation on transcriptional variation. One major conclusion is that stabilizing selection must constrain the divergence of gene expression profiles in natural populations.

Inversin is a component of a poorly understood cilia-based mechanism responsible for specifying the left-right axis during development and for maintaining normal kidney architecture throughout life. A new study now suggests that inversin might act as a flow-regulated molecular switch between canonical and noncanonical Wnt pathways, providing insights into the mechanisms underlying cilia-based signaling processes.

Epistasis analysis is a foundation in the analysis of genetic networks, but in complex or poorly defined processes, defining the phenotype can be an insurmountable hurdle. A new study shows that microarray expression profiles can be used as a 'phenotype' for epistasis analysis of the development of a multicellular organism, offering a potentially universal solution to this problem.

Children and young adults with sickle cell anemia at risk for stroke are identified principally by screening for cerebral vasculopathy using transcranial Doppler ultrasonography. Investigators now show how Bayesian networks can generate useful predictive models and highlight relationships between genes and the occurrence of stroke in those with sickle cell anemia.

The first empirical test of an evolutionary theory provides support for a mutational landscape model underlying the process of adaptation. The study shows that it is possible to predict at least the first step in an adaptive walk and also shows the importance of incorporating mutation bias in the fitness effects of mutations.

The genetic culprits that contribute to common diseases remain at large, despite dedicated sleuthing by many laboratories. A new study evaluates the power of genome-wide searches for variants acting in combination, with results that are both unexpected and encouraging.

Sir2 deacetylases are believed to promote the survival and longevity of organisms during times of adversity. A new study shows that activation of Sir2 by small molecules called sirtuin-activating compounds increases neuronal survival in two different models of Huntington disease, possibly opening new avenues for treatment.

The X chromosome has traditionally been characterized as a conscientious sister to her derelict brother that is the Y. Beyond dutifully maintaining the family heritage, however, the X has developed its own unique identities. Now, the complete sequence of the human X allows us to appreciate its distinctiveness at an unprecedented resolution.

The mechanism by which cytosine methylation stably represses transcription is of great interest. A new study provides evidence associating DNA methylation, MeCP2 and the SWI/SNF chromatin-remodeling factor, implicating local chromatin architecture in DNA methylation–dependent transcriptional repression.

Like most organisms, yeast has relatively few genes that are necessary for viability. The presence of a duplicate gene elsewhere in the genome underpins many cases of dispensability. A new study suggests that the backup mechanism is more complex than previously assumed and requires feedback loops that ensure transcriptional upregulation of the duplicate.

Proving that aberrant CpG island methylation has a functional role in human tumorigenesis is a chief goal in cancer epigenomics. A study now shows that a predictable mouse model of acute lymphocytic leukemia faithfully recapitulates the pattern, targets and frequency of aberrant methylation observed in its human counterpart and may soon allow the timing, and perhaps even the cause, of aberrant CpG island methylation to be investigated.

Gene expression microarray data on each individual in a pedigree or from an experimental cross enable the identification of the genetic determinants of variation in gene expression. Three new studies apply this approach to rodent recombinant inbred lines and provide new insights into the nature of variation in gene expression and its connection to disease.

Dynamins are dynamic scaffolding proteins that function in membrane trafficking. A new study shows that mutations in the gene encoding dynamin 2 underlie a distinct form of peripheral neuropathy, establishing the first link between dynamins and human disease.