Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Diffusible signal molecules controlling cell differentiation and patterning in Dictyostelium

Slime moulds, such as Dictyostelium discoideum, have biochemical, physiological and probably developmental features in common with both plants and animals. During development separate Dictyostelium amoebae first aggregate into collecting centers to form small multicellular organisms which, in their slug form, can migrate over the substratum toward light. Eventually a slug culminates to form a fruiting body consisting of a cellular stalk supporting a mass of spores. Development is highly regulative, indicating that it is controlled by signalling between the cells. A number of diffusible signal molecules have been discovered, including cyclic AMP, the chemoattractant in aggregation, and DIF-1, a novel chlorinated phenyl alkanone, which acts as a specific inducer of stalk cell differentiation. The migrating slug contains three types of precursor cell: prespore, prestalk A and prestalk B cells. Differentiation of these cells from uncommitted amoebae can be brought about in cell cultures by cyclic AMP and DIF-1 acting in combination: cyclic AMP alone favours prespore, DIF-1 alone favours prestalk B, cyclic AMP and DIF-1 together favour prestalk A cell differentiation. There is evidence suggesting that these signals act in the same way in the intact aggregate. A cytoplasmic DIF-1 binding protein has been discovered, whose level increases as cells become sensitive to DIF-1 and which binds DIF-1 with an affinity and specificity suggestive of a receptor. At the same time, cells are able to inactivate DIF-1 by a metabolic pathway involving at least 12 metabolites. Metabolism may also serve to produce gradients of DIF-1 in the aggregate or other signal molecules from DIF-1. Manipulation of the DIF-1 signalling system will be an important means of further elucidating its role in development

Volumetric and area-based breast density measurement in the predicting risk of cancer at screening (PROCAS) study

Mammographic density, defined as the proportion of the breast area in a mammogram that contains fibroglandular tissue, is associated with risk of breast cancer. However, measures of mammographic density are subject to variation in the underlying imaging process and in the assessments of observers. Automatic volumetric measures of breast density remove much of this variability, but their association with risk is less well established. We present density measurements produced using area-based visual analogue scales (VAS) and by volumetric assessment software (QuantraTM, Hologic Inc.) in the PROCAS study. The distributions of VAS scores (n = 22 327) and volumetric quantities (n = 11 653) are given, as are their relationships for subjects with results by both (n = 11 096), but these are not directly comparable as one is area-based and the other volumetric. Inter-observer variability in visual area-based estimation is examined by a scatter plot matrix