Despite a reputation for impenetrable bureaucracy, the European Union has in place two relatively elegant funding mechanisms for the critical transitions of a scientist's career: for the PhD moving into postdoctoral research, and for outstanding researchers launching their first independent research programs.
The usefulness of the rat as a genetic model of complex traits and disease is increasing, with the development of a number of genome-wide resources enabling high-resolution genetic analysis. This special focus on rat genetics surveys the landscape and highlights the range of discoveries that are now possible.
It has been four years since the original publication of the draft sequence of the rat genome. Five groups are now working together to assemble, annotate and release an updated version of the rat genome. As the prevailing model for physiology, complex disease and pharmacological studies, there is an acute need for the rat's genomic resources to keep pace with the rat's prominence in the laboratory. In this commentary, we describe the current status of the rat genome sequence and the plans for its impending 'upgrade'. We then cover the key online resources providing access to the rat genome, including the new SNP views at Ensembl, the RefSeq and Genes databases at the US National Center for Biotechnology Information, Genome Browser at the University of California Santa Cruz and the disease portals for cardiovascular disease and obesity at the Rat Genome Database.
Genome-wide association studies have identified many variants affecting susceptibility to disease. Now, three studies use this approach to study adult height variation in a combined sample size of ?63,000 individuals and report a total of 54 validated variants influencing this trait.
Principal component analysis (PCA) has been a useful tool for analysis of genetic data, particularly in studies of human migration. A new study finds evidence that the observed geographic gradients, traditionally thought to represent major historical migrations, may in fact have other interpretations.
Gene expression can be an indicator of cellular state, and studies characterizing variation in gene expression have been useful on the cellular level. Two new studies now provide the first direct demonstration of the successful use of the multidimensionality of gene expression to dissect the genetic architecture of complex diseases.
The progression of carcinomas to high-grade malignancies is accompanied by profound histological changes in the tumor-associated stroma. Although previous studies have suggested that mesenchymal cells of the stroma undergo genetic alterations during this progression, a new study now provides evidence that strongly contradicts this theory of stromal cell coevolution.
Recessive loss-of-function mutations in genes involved in renal NaCl handling cause rare diseases characterized by salt wasting and reduced blood pressure of variable severity. A new study shows that the carrier state for rare inactivating mutations in three genes involved in NaCl transport in the kidney is associated with a significant blood pressure reduction and a reduced risk of hypertension in the general population.
Iron deficiency is usually attributed to chronic blood loss or inadequate dietary intake. Here, we show that iron deficiency anemia refractory to oral iron therapy can be caused by germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the systemic iron regulatory hormone hepcidin. These findings demonstrate that TMPRSS6 is essential for normal systemic iron homeostasis in humans.
Recently, TDP-43 was identified as a key component of ubiquitinated aggregates in amyotrophic lateral sclerosis (ALS), an adult-onset neurological disorder that leads to the degeneration of motor neurons. Here we report eight missense mutations in nine individuals?six from individuals with sporadic ALS (SALS) and three from those with familial ALS (FALS)?and a concurring increase of a smaller TDP-43 product. These findings further corroborate that TDP-43 is involved in ALS pathogenesis.
