Reviews & Analysis

Mutations in SCL2A10, encoding a glucose transporter, result in arterial tortuosity syndrome, indicating a link between glucose metabolism and angiopathic changes. Intriguingly, some of the phenotypic effects of SCL2A10 ablation may be mediated by upregulation of TGFβ signaling, suggesting new approaches for therapy of aortic aneurysm.

A new study reports that two common loss-of-function mutations in the gene encoding filaggrin are important risk factors for atopic dermatitis, and interestingly, for asthma in association with atopic dermatitis, but not asthma in the absence of atopic dermatitis. These findings suggest the importance of the epidermal barrier in preventing sensitization to allergens.

A new study uses an evolutionary approach to characterize the diversity within populations of cells in Barrett's esophagus lesions. Greater genetic clonal diversity is found to be associated with higher risks for transformation.

Special chromosome marks are thought to maintain the stable pattern of gene expression that underlies cell identity. Surprisingly, similar chromosome marks accompany cyclic gene expression driven by the 24-hour circadian clock.

A new study profiles microRNA (miRNA) expression in mouse epidermis and hair follicles and examines the requirement for these miRNAs during normal embryonic development. In the absence of Dicer-dependent miRNA production, hair follicles evaginate rather than invaginate, revealing an unexpected role for miRNAs in regulating hair follicle morphogenesis.

Mutations in components of the planar cell polarity pathway in mammals give rise to neural tube defects, anomalous cochlear hair cell stereocilia and kidney cysts. A new study suggests that two planar cell polarity components initially characterized in flies are required for ciliogenesis and Hedgehog signaling in frog embryos, providing insights into the mechanisms governing positioning and growth of the ciliary axoneme.

Human embryos that develop in the presence of chromosomes solely of paternal origin give rise only to a disorganized mass of placental derivatives known as a complete hydatidiform mole. A new study reports that mutations in NALP7, a gene thought to be involved in inflammatory and apoptotic pathways, occur in human females whose biparental conceptuses can develop as apparent complete moles.

Neural tube defects (NTDs) represent a broad and complex class of brain malformations, and despite much progress in understanding their etiology, many facets of neural tube development and closure remain obscure. Two new studies report the identification of the first two genes responsible for Meckel-Gruber syndrome, one of the major contributors to syndromic NTDs, and implicate defective cilia in its pathogenesis.

Anthrax lethal toxin lyses macrophages derived from certain inbred mice but not others, forming the basis of a bioassay widely used in the development of antibodies and drugs to treat anthrax. A new study identifies two genes essential for this lysis, revealing potential links between toxin-induced proteolysis and cellular killing.

The sequence of a second chimpanzee Y chromosome has been determined. It confirms the degradation of four genes on the chimpanzee lineage, reveals the recent gain of one on the human lineage and emphasizes the low Y-chromosomal genetic diversity within western chimpanzees.

Common cardiovascular diseases are expressed as genetically complex traits, and identifying the underlying genes is difficult. A new study provides resources required for a more integrative view of cardiovascular systems.

An important role of RNA interference (RNAi)-like pathways in plants is defense against viral infection. Viruses can overcome this defense by expressing proteins that suppress the pathway. A new study of Agrobacterium tumefaciens infection reveals that this plant pathogen, although a bacterium, also induces and then suppresses the host RNAi response.

A new study shows that mutations in the gene encoding carboxyl ester lipase (CEL) cause beta cell dysfunction and early-onset diabetes. As this gene is expressed in the exocrine, and not the endocrine, pancreas, its identification challenges many of our preconceived ideas about the causes of beta cell dysfunction in diabetes.

SNP genotyping platforms have been used to discover ∼1,000 deletion structural variants within the human genome, with median lengths ranging from 500 bp to 10.5 kb. Analyses of a subset of these provide compelling evidence of linkage disequilibrium with flanking SNPs.

A new study shows that some cases of early-onset Alzheimer disease result from duplications of the APP locus, which encodes the amyloid β precursor protein. This finding fulfills a 20-year-old prediction that genetic variability in APP expression could lead to disease and provides further, perhaps definitive, evidence for the amyloid hypothesis of the disorder.