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Sequencing of genomes, including that of humans, has revolutionized our understanding of genome organization and accelerated the hunt for disease-causing mutations. New studies by the Human Epigenome Project (HEP) now highlight the importance and complexity of cytosine DNA methylation in tissue-specific regulation of gene expression.
Many clinical syndromes result from deletion or duplication of regions within the human genome. Two new studies demonstrate strong connections between such events and allelic recombination in humans, which in the future may enable researchers to better predict the locations of unstable genomic regions.
A new study reports mutations in PLCE1 responsible for an autosomal recessive nephrotic syndrome in children that presents with diffuse mesangial sclerosis or focal segmental glomerulosclerosis. Remarkably, two affected individuals treated at an early phase of life responded to either steroids or cyclosporin A, opening a window of opportunity for therapy.
Analysis of the phenotype of mouse germ cells deficient for the retinoic acid–responsive gene Stra8 provides insight into the timing of the commitment to enter meiosis in mammals. The observations suggest that, as in other eukaryotes, this commitment precedes (or coincides with) the commitment to premeiotic DNA replication.
The recently completed International HapMap Project has provided detailed information about patterns of genetic variation in four different population samples. Two new studies show that the patterns of variation documented in the HapMap can be applied to other human populations, suggesting it is time to establish a standardized platform for all whole-genome association studies.
A new study shows that during transcription, the TH2 interleukin gene cluster is organized into several small chromatin loops connected at their base by the protein SATB1. This first detailed glimpse of chromatin folding provides a new perspective on the coordination of cell type–specific gene expression.
Female-to-male sex reversal is an extremely rare and puzzling phenomenon. A new study identifies mutations in the gene encoding R-spondin1 in XX sex-reversed individuals and suggests that antagonistic pathways in the bipotential gonad regulate sex determination.
Two new reports extend the functions of DMP1, a bone matrix protein involved in mineralization, to phosphate regulation. These discoveries provide insight into the mechanism by which bone may coordinate systemic phosphate balance with the needs of mineralizing bone.
Reactive oxygen species (ROS) are traditionally viewed as the toxic by-product of cellular respiration. A new study suggests a homeostatic role for ROS in maintaining stable respiratory phenotypes across genetic variants of the mitochondrial genome.
Transcriptional cis-regulatory modules have a fundamental role in regulating eukaryotic gene expression. A new study shows how computational modeling can test hypotheses about how regulatory elements function, with results that challenge conventional views of their organization.
New experimental approaches combined with statistical models show that DNA sequence strongly influences how the genome is packaged into nucleosomes. The studies predict that genes regulated by fundamentally different mechanisms have distinct nucleosome positioning signatures encoded in their DNA.
Full-genome tiling arrays provide powerful biological evidence to support gene predictions and suggest the need for new and improved annotations. New studies using tiling arrays of the Drosophila melanogaster genome show that 85% of the fly genome is transcribed and processed into mature transcripts, representing 30% of the fly genome.
Precise control of sodium excretion by the kidney is critical for maintaining fluid and electrolyte homeostasis. A new mouse model provides compelling evidence that a kinase, WNK4, provides key signals for regulating blood pressure and potassium balance by controlling the structure and function of the distal convoluted tubule.
Many submicroscopic genomic rearrangements have been robustly associated with well-defined clinical syndromes. Three papers in this issue once again illustrate how underlying genomic architecture can catalyze rearrangement causing sporadic disease, and they further suggest that widespread clinical implementation of high-resolution genome analysis may identify the cause of traits previously intractable to conventional genetic analyses.
A new study shows that normalizing the number of CUG repeat–containing DMPK transcripts in a mouse model of myotonic dystrophy reverses the myotonia and cardiac conduction defects. This discovery suggests new therapeutic approaches for the disease.
