News & Views in 2005

A proportion of wild mice carry a variant region of chromosome 17 that results in severe transmission ratio distortion in males. The genetic basis of this distortion has long been enigmatic, but a recent study begins to disentangle it.

A new study describes the use of an alternative splicing microarray to identify exons regulated by the neural-specific Nova splicing factors. Nova2 is also shown to coordinately regulate splicing of a group of functionally related genes that encode a network of interacting proteins at the synapse.

Primary immunodeficiencies, ranging from mild to very severe, comprise more than 50 different entities in which part of the body's immune system is missing or does not function properly. Two studies now report defects in the TNFR family member TACI associated with two forms of human immunodeficiency.

Applied genomics has focused on correlating clinical phenotypes with qualitative differences in DNA sequence such as variations in SNPs. A new study adds a third dimension, allele-specific copy-number differences, combining quantitative and qualitative approaches to understand the relationship between genetic variation and clinical outcome.

RNA-based silencing mechanisms suppress gene expression through the sequence-specific activity of small RNAs. New studies in plants now identify atypical RNA polymerases that promote and maintain transcriptional silencing.

Autosomal dominant focal segmental glomerular sclerosis is a kidney disease that leads to progressive renal failure. Now, new studies show that mutations in the cation channel TRPC6 underlie this hereditary kidney disorder and establish a molecular link between TRPC6 and structural components of the glomerular slit diaphragm.

A new study of dominant negative functions in cells infected by a positive-strand RNA virus detects an array of locus- and allele-specific effects. Exploiting subunit defects in multi-component complex assemblies provides a new approach to identifying targets for antiviral therapies that may inhibit the emergence of drug-resistant RNA virus populations.

Until very recently, it was widely touted that the complete DNA sequences of any two human beings were 99.9% identical. A new study refutes this notion through a comprehensive comparison of two individual genomes which detects hundreds of new structural genomic variants.

The spindle checkpoint delays the cell cycle when chromosomes are not properly attached to the mitotic or meiotic spindle, giving cells time to correct the error. A new study now strengthens the connection between checkpoint failure and human aneuploidies by showing that the spindle checkpoint component Mad3p is required for accurate segregation of meiotic chromosomes that have not recombined with each other.

Yeast's ability to produce ethanol in high concentrations has been exploited by humans for millennia. Two recent papers help us to understand the genetic changes that made this species so appealing to humans and the history of its domestication.

Single-sperm genotyping has provided evidence for hot spots of locally intense recombination in humans. Previous efforts have shown that statistical methods can identify these hot spots as local deficits of linkage disequilibrium, but a report in this issue shows that some recombination hot spots leave no signature of reduced linkage disequilibrium.

The restriction of herpesvirus by natural killer cells, initiated before the acquired immune response, illustrates the value of innate immune mechanisms for viral containment. Now, a new study shows that the activating natural killer cell receptor Ly49P and the major histocompatibility complex class I H-2D^k molecule act in concert to restrict mouse cytomegalovirus infection, identifying a new mechanism of host resistance.