In mice, null mutations of the breast cancer susceptibility gene Brca1 result in embryonic lethality. In the May 15 Genes & Development, Ludwig et al. describe the generation of a mutant mouse that expresses a truncated Brca1 protein that mimics mutations found in human breast cancer patients (Genes & Development 2001, 15:1188-1193). They used a two-step 'knock-in' targeting strategy to insert a stop codon in Brca1 exon 11. The genetic background of the mice determined the extent of embr

Overexpression of the c-myc oncogene induces multistaged neoplastic progression leading to B-cell lymphomas in the bursa of Fabricius. In the May 22 Proceedings of the National Academy of Sciences, Neiman et al. describe the use of microarray analysis to define the genetic networks important for myc-induced lymphomagenesis (Proc Natl Acad Sci USA 2001, 98:6378-6383). The authors created a customized cDNA microarray containing over 2,200 genes associated with the immune system - details can be fo

Chromosome 4 of Drosophila melanogaster is an atypical autosome, exhibiting several features characteristic of the X chromosome. In the May 22 Proceedings of the National Academy of Sciences, Larsson et al. report the molecular cloning of Painting of fourth (Pof), which encodes a protein that specifically paints chromosome 4 (Proc Natl Acad Sci USA 2001, 98:6273-6278). The POF protein sequence contains a putative RNA-binding domain. POF protein decorates chromosome 4 by spreading out from an ini

In the May 18 Science, Farber et al. report the use of fluorescently quenched phospholipid substrates to screen for genes affecting lipid metabolism in living zebrafish larvae (Science 2001, 292:1385-1388). The lipids were swallowed by the larvae and cleaved by lipases in the intestine before the fluorescent metabolites were transported to the liver and gall bladder. The assay demonstrated lipid metabolism defects in zebrafish mutants that have abnormal digestive organ morphology, as well as the

Comparative proteome analysis identifies just 40 genes that are candidates for lateral transfer from bacteria to vertebrates.

Apoptotic bodies are rapidly cleared in the body by phagocytosis. In the May 22 Proceedings of the National Academy of Sciences, Bergsmedh et al. provide evidence that the uptake of apoptotic bodies can deliver oncogenes to the phagocytotic host cell (Proc Natl Acad Sci USA 2001, 98:6407-6411). They could detect the horizontal transfer of H-rasV12 or c-myc oncogenes from dying, transformed rat fibroblast cells to recipient mouse fibroblasts. DNA transfer was detected by PCR analysis and fluoresc

functions in the developmental control of methylation and chromatin remodelling.

The 'Out-of-Africa' hypothesis posits that modern humans derive from an African originator population, that spread outward replacing local populations approximately 100,000 years ago. In the May 11 Science, Ke et al. report the use of Y chromosome polymorphism analysis to test the origins of modern Asian man (Science 2001, 292:1151-1153). They looked at 12,127 men from 163 different populations across Southeast and Central Asia and typed three Y chromosome biallelic markers (YAP, M89 and M130).

Linkage disequilibrium (LD) refers to the correlation among neighboring alleles, reflecting common haplotype ancestry. In the May 10 Nature, Reich et al. describe a systematic, genome-wide analysis of LD within human populations (Nature 2001, 411:199-204). They analyzed 19 random chromosomal regions, each of which centers around a core SNP (single length polymorphism) in the coding region of a gene. Extensive sequencing of 44 individuals from Utah identified 272 'high frequency' SNPs at 0-160 ki

Neuronal apoptosis plays a critical role in the development of the nervous system and in neurodegenerative disease. In the Early Edition of the Proceedings of the National Academy of Sciences, De Zutter and Davis report a study of pro-apoptotic, neuronal gene expression and the identification of monoamine oxidase (MAO) as a death-inducing gene. They used the well-studied neuronal pheochromocytoma PC12 model, which undergoes apoptosis when deprived of neurotrophic growth factor (NGF). The authors

A recent hypothesis suggests that the type of genetic instability in cancers is the result of Darwinian selection pressures exerted by specific carcinogens. In the May 8 Proceedings of the National Academy of Sciences, Bardelli et al. describe experiments to test whether chromosomal instability (CIN) is induced by bulky-adduct-forming agents, whereas microsatellite instability is selected by methylating agents (Proc Natl Acad Sci USA 2001, 98:5770-5775). They used a variant colorectal cell line,

Large-scale methods for gene profiling or protein quantification are the focus of genomic and proteomic studies. But new approaches are needed to integrate these data sets and create biological models that can predict cellular behaviour. In the May 4 Science, Ideker and colleagues, at the Institute for Systems Biology in Seattle, describe an integrated approach to create a model of cellular metabolic pathways (Science 2001, 292:929-934). Their approach is based on four steps: defining all the ge