Reviews & Analysis

A new study finds that copy number variation in the salivary amylase gene in humans is associated with amylase concentration in saliva and average starch consumption in populations. This provides a striking example of the role of copy number variants (CNVs) in adaptive evolution, and of diet in producing selective pressures.

Two reports present detailed analyses of the haplotype structure of widely used laboratory mice based on resequencing data from 15 inbred strains. The studies provide the deepest view thus far of the patterns of genetic variation segregating in the inbred lines, and have implications for the design of complex trait mapping studies in mice.

The report of a haplotype map for the selfing plant Arabidopsis thaliana has uncovered numerous major-effect polymorphisms and rapid linkage disequilibrium decay. This work lays the foundation for genome-wide association studies at near-gene-level resolution in a model organism possessing substantial functional diversity and extensive community resources.

The discovery of genetic risk factors for multiple sclerosis has proven difficult. IL-7Rα, encoded by IL7R, is a pleiomorphic cytokine receptor now implicated in the pathogenesis of multiple sclerosis in independently replicated genetic association studies.

Identical mutations of the same genes can lead either to congenital malformations or to cancer, depending on their cellular and temporal context. The demonstration of activated RAS-ERK signaling in a mouse model of Apert syndrome suggests that drugs designed to inhibit this pathway in cancer may also delay the progression of several serious pediatric syndromes.

A 23-nucleotide sequence conserved in species from rice to Arabidopsis thaliana in a family of noncoding RNAs resembles a cleavable miRNA target site—but not exactly. A new study demonstrates that the site is not cleaved and instead negatively regulates miRNA activity through mimicry.

Several devastating genetic diseases illustrate that peroxisomes are essential to the development and functioning of the central nervous system. New work using a mouse model now shows that peroxisome integrity in oligodendrocytes is essential for axonal maintenance.

Two genome-wide association studies report three loci predisposing to restless legs syndrome, a common sleep disorder also associated with periodic limb movements during sleep. The identified variants account for a large portion of population-attributable risk in individuals of European ancestry and may preferentially affect various symptoms of the disorder.

Genome-wide association studies, exemplified by the Wellcome Trust Case Control Consortium and follow-up studies, have identified dozens of common variants robustly associated with common diseases, providing new clues about genetic architecture in humans. Finding all such loci, and fully defining genotype-phenotype correlation, will be a key to translating initial clues into pathophysiological understanding and clinical prediction.

Human genome-wide association studies pose a challenge in identifying significant disease associations from nearly half a million statistical tests. A new report describes an especially promising approach, recently applied to the Wellcome Trust Case Control Consortium data sets, that uses the correlated structure of genomic variation to impute genotypes at missing sites and to test association with both observed and imputed SNPs.

The much-anticipated publication of the ENCODE pilot project, representing a detailed and comprehensive characterization of 1% of the human genome, has demonstrated how little we truly understand about how our genes are regulated. Transcripts are nearly everywhere, regulatory sequences remain poorly defined and evolutionary conservation is a surprisingly inadequate predictor of transcriptional features.

Wnt signaling regulates several aspects of development and tissue homeostasis. Two new studies in this issue uncover the underlying mechanism for focal dermal hypoplasia, a multiorgan developmental disorder, and underscore the important role of Wnt proteins in ectodermal-mesodermal communication.

The list of genetic diseases associated with dysfunction of primary cilia continues to expand. Two new studies add to this growing body of literature and provide a fascinating example of the clinical variability associated with ciliary disorders.