Reviews & Analysis

Several mutant strains of mice have dark skin pigmentation due to an aberrant accumulation of pigment-producing melanocytes in the dermal layer of the skin. A new study shows that three such strains carry activating mutations in the genes encoding the G-protein subunits Gαq or Gα11, resulting in more pigment cell precursors and an excess of dermally retained pigment cells at birth.

The combination of inhibition of RNA degradation and comparative genomic scanning is a powerful new method for detecting gene disruptions. The utility of the method is well-illustrated by a series of observations linking the ephrin receptor EPHB2 to prostate cancer.

The benign-to-malignant transition in human breast cancer is associated with a marked increase in chromosomal aberrations. A new study suggests that telomere dysfunction and its associated bridge-fusion-breakage cycles may drive this episodic instability, thereby providing aspiring cancer cells with the multiple genetic aberrations needed to achieve a fully malignant state.

Mice deficient in the metalloprotease inhibitor TIMP3, which inhibits the tumor-necrosis factor alpha (TNF-α)-converting enzyme (TACE, also called ADAM17), have elevated levels of TNF and severe inflammation in the liver. This result confirms the physiological importance of the soluble form of TNF and identifies TIMP3 as a crucial regulator of this inflammatory cytokine.

Vascular endothelial growth factor (VEGF) stimulates angiogenesis, protects neurons from ischemic and degenerative disorders, and triggers the birth of new nerve cells in the adult brain. Now we discover that it is also important for memory and learning.

The extent and nature of sequence variation in segmental duplications, which is widespread in the human genome, is poorly understood. A new study provides valuable insights into this issue.

Two new papers report advances in the understanding of the GNAS complex locus of overlapping and oppositely directed transcripts that are subject to genomic imprinting.

A comprehensive microarray-based analysis of the cell cycle shows that periodic transcription of most genes is not conserved between Schizosaccharomyces pombe and Saccharomyces cerevisiae. A core group of ∼40–80 genes have conserved patterns of transcription and may have key roles in cell cycle progression.

Inactivating mutations in TGFBR2, encoding the transforming growth factor-β (TGFβ) type 2 receptor, may account for up to 10% of cases of Marfan syndrome. This finding has implications for a wider spectrum of disorders, including cancer, fibrosis and inflammatory and cardiovascular diseases, which are influenced by TGFβ.

Schizophrenia is a severely disabling disorder with a lifetime risk of ∼1%, which accounts for 2.8% of the global burden of disease. A new study provides evidence that a third gene in the 22q11 region is associated with schizophrenia, further confounding an already complicated story.

Factors that modify chromatin are crucial for regulating gene expression, but what, in turn, regulates these factors? A new study highlights the importance of signaling cascades in recruiting chromatin-remodeling enzymes to specific promoters during muscle differentiation.

The discovery that a differentiated somatic cell can give rise to a new organism through nuclear transfer cloning touched off a revolution in genetics. A new study outlining how to target genes serially in cows ushers in a new era in large-animal genetics.

The nucleotide excision repair system is essential for repairing DNA damage caused by exposure to sunlight. Now, parallel studies in yeast and individuals with a rare disease called trichothiodystrophy have identified a new component of the DNA repair and basal transcription factor TFIIH.

The acquisition of an abnormal number of chromosomes is a hallmark of many human cancers. A new study indicates that unequal segregation of genetic material to daughter cells during cell division can also lead to premature senescence and accelerated onset of a variety of aging phenotypes.