News & Views in 2005

Although the correlation between maternal age and meiotic nondisjunction in human oocytes is widely recognized, the underlying molecular defects are largely unknown. New evidence from mice lacking SMC1β suggests that high levels of chromosome mis-segregation in older oocytes may be due in part to deterioration of meiotic sister-chromatid cohesion during aging.

The protein tyrosine phosphatase PTPN22 (also called LYP) is the leading example of a genetic variant that confers risk of developing diverse human autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, autoimmune thyroid disease and systemic lupus. A new study now shows that the PTPN22 risk-associated variant, Trp620, results in a gain of PTPN22 phosphatase activity in T cells, opening up new avenues for exploring disease mechanisms.

Genome-wide association studies have the potential to identify systematically the contributions of common genetic variants to human disease, but the tools to carry out such studies have been incomplete. Assessments of the HapMap resource suggest that the tools are now in hand, but care is required in their use for study design, analysis and interpretation.

Mutations in SIL1, which encodes a nucleotide exchange factor for the chaperone BiP, cause a progressive multisystem disorder that probably results from abnormal protein quality control in the endoplasmic reticulum.

Sickle hemoglobin and α-thalassemia evolved as two of the most common human genetic polymorphisms because they confer protection against malaria. New evidence suggests that their effects may interfere with each other, raising questions about these hemoglobinopathies and their mechanisms of protection.

A new study shows that defects in SECIS-binding protein 2 (SBP2), a factor required for incorporation of selenium into proteins, produce alterations in thyroid hormone metabolism in humans but none of the other effects attributed to selenium deficiency or loss of selenoproteins. This finding suggests that SBP2 has a role in distinguishing between selenoproteins whose functions are essential and those with supporting roles in life and health.

An endosomal ferric reductase has long been implicated in the transferrin cycle. Identification of the gene mutated in a genetic anemia in mice uncovers a new family of ferric reductase enzymes involved in reduction of transferrin-bound iron.

Although RNA interference has become a useful genetic technique, effective and stable knock-down of vertebrate genes remains a challenge, especially in vivo. A new approach, which uses RNA polymerase II to generate small interfering RNAs, not only seems to be more effective than previous approaches but also allows tightly regulated RNA interference in culture and in vivo.

A new study of mice lacking Prox1, a gene required for the formation of lymphatic endothelial cells, unveils a link between lymph fluid and fat deposition. These findings bring the lymphatic vascular system into the focus of obesity research.

Asymmetric division of stem cells results into two unequal daughter cells, only one of which resembles the parent stem cell. A new study provides genetic evidence in Drosophila melanogaster that the disturbance of this delicately balanced process in neuronal stem cells induces a cancer-like state.

The ability of crop plants to tolerate high salt concentrations is an agriculturally useful trait. A new study in rice shows that allelic variation in OsHKT8, which encodes a Na⁺ transporter, contributes to the enhanced capacity of a salt-tolerant variety to maintain shoot K⁺ homeostasis under NaCl stress.

Transcription-coupled nucleosome turnover provides an opportunity to incorporate new nucleosomes at active genes. Swapping nucleosomes that contain silencing marks with those that are more permissive for transcription may provide a mechanism for remembering the activity state of a gene through the cell cycle.

Cancer metastasis has historically been viewed in the context of the mutational spectra arising during development of the primary cancer. The identification of a new modifier of cancer metastasis efficiency in mice provides experimental support for a predisposition model in which metastatic potential is viewed as a heritable trait influenced by host genetic polymorphisms.

How the Fanconi anemia chromosome stability pathway functions to cope with interstrand crosslinks and other DNA lesions has been elusive. The identification of two new Fanconi anemia–associated proteins with helicase motifs, FANCM and BRIP1 (also called FANCJ or BACH1), implicates the FANC nuclear core complex in recognizing or processing damaged DNA and the BRIP1 helicase as acting independently of this complex.

The first replicating molecules were probably composed of RNA and undoubtedly small, limited in size by a self-destructing error rate. A new study shows that a relatively minor increase in replication fidelity may have had a large effect on the size, and hence complexity, of early replicators.

Molecular noise, or random fluctuations in the levels of cellular components, arises spontaneously when there are small numbers of molecules and is transmitted to dependent processes. A new study shows how noise propagates through gene expression in yeast and shows that chromosomal position has a more central role than previously thought.