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Inheritance and variation were a major focus of Charles Darwin's studies. Small inherited variations were at the core of his theory of organic evolution by means of natural selection. He put forward a developmental theory of heredity (pangenesis) based on the assumption of the existence of material hereditary particles. However, unlike his proposition of natural selection as a new mechanism for evolutionary change, Darwin's highly speculative and contradictory hypotheses on heredity were unfruitful for further research. They attempted to explain many complex biological phenomena at the same time, disregarded the then modern developments in cell theory, and were, moreover, faithful to the widespread conceptions of blending and so-called Lamarckian inheritance. In contrast, Mendel's approaches, despite the fact that features of his ideas were later not found to be tenable, proved successful as the basis for the development of modern genetics. Mendel took the study of the transmission of traits and its causes (genetics) out of natural history; by reducing complexity to simple particulate models, he transformed it into a scientific field of research. His scientific approach and concept of discrete elements (which later gave rise to the notion of discrete genes) also contributed crucially to the explanation of the existence of stable variations as the basis for natural selection. Keywords Variations * Discreteness * Gradualism * Statistical laws * Chance * Blending inheritance * Soft inheritance * Pangenesis * Mendel * Darwin, 1 Introduction The emergence of the science of genetics began as a result of the fruitful application of both the research methods and the concept of discrete 'elements' (which later [...]

Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

With the availability of high-density marker maps and cost-effective genotyping, genomic selection methods may provide faster genetic gain than can be achieved by current selection methods based on phenotypes and the pedigree. Here we investigate some of the factors driving the accuracy of genomic selection, namely marker density and marker type (i.e., microsatellite and SNP markers), and the use of marker haplotypes versus marker genotypes alone. Different densities were tested with marker densities equivalent to 2, 1, 0.5, and 0.25[N.sub.e] markers/morgan using microsatellites and 8, 4, 2, and 1[N.sub.e] markers/morgan using SNP, where 1[N.sub.e] markers/morgan means 100 markers per morgan, if effective size ([N.sub.e]) is 100. Marker characteristics and linkage disequilibria were obtained by simulating a population over 1,000 generations to achieve a mutation drift balance. The marker designs were evaluated for their accuracy of predicting breeding values from either estimating marker effects or estimating effects of haplotypes based upon combining 2 markers. Using microsatellites as direct marker effects, the accuracy of selection increased from 0.63 to 0.83 as the density increased from 0.25[N.sub.e]/morgan to 2[N.sub.e]/morgan. Using SNP markers as direct marker effects, the accuracy of selection increased from 0.69 to 0.86 as the density increased from 1[N.sub.e]/morgan to 8[N.sub.e]/morgan. The SNP markers required a 2 to 3 times greater density compared with using microsatellites to achieve a similar accuracy. The biases that genomic selection EBV often show are due to the prediction of marker effects instead of QTL effects, and hence, genomic selection EBV may need rescaling for practical use. Using haplotypes resulted in similar or reduced accuracies compared with using direct marker effects. In practical situations, this means that it is advantageous to use direct marker effects, because this avoids the estimation of marker phases with the associated errors. In general, the results showed that the accuracy remained responsive with small bias to increasing marker density at least up to 8[N.sub.e] SNP/morgan, where the effective population size was 100 and with the genomic model assumed. For a 30-morgan genome and [N.sub.e] = 100, this implies that about ~24,000 SNP are needed. Key words: accuracy of selection, breeding value estimation, dense marker map, genome-wide selection, marker-assisted selection

Enhancer DNA decoy oligodeoxynucleotides (ODNs) inhibit transcription by competing for transcription factors. A decoy ODN composed of the cAMP response element (CRE) inhibits CRE-directed gene transcription and tumor growth without affecting normal cell growth. Here, we use DNA microarrays to analyze the global effects of the CRE-decoy ODN in cancer cell lines and in tumors grown in nude mice. The CRE-decoy up-regulates the AP-2[beta] transcription factor gene in tumors but not in the livers of host animals. The up-regulated expression of AP-2[beta] is clustered with the up-regulation of other genes involved in development and cell differentiation. Concomitantly, another cluster of genes involved in cell proliferation and transformation is down-regulated. The observed alterations indicate that CRE-directed transcription favors tumor growth. The CRE-decoy ODN, therefore, may serve as a target-based genetic tool to treat cancer and other diseases in which CRE-directed transcription is abnormally used.

Using selectable genes as proof of principle, a new high-through-put genotype-based mutation screen in mouse embryonic stem (ES) cells was developed [Chen et al. (2002) Nat. Genet. 24, 314-317]. If expanded to nonselectable genes, this approach would allow one to proceed quickly from sequence to whole-animal phenotypes. Here data are presented showing that a screen of a cryopreserved library of clonal, germ line competent, N-ethyl-N-nitrosurea (ENU) mutagenized ES cells can identify a large series of allelic mutations in Smad2 and Smad4, two nonselectable genes of the transforming growth factor [beta] superfamily of signaling molecules. Whole animal phenotypic analyses of some of these alleles provided evidence for novel developmental processes mediated by these components of transforming growth factor [beta] signaling, demonstrating the utility of non-null alleles created by chemical mutagens. The accurately assessed mutation load of the ES cell library indicates that it is a valuable resource for developing mouse lines for genetic and functional studies. This methodology can conceptually be applied for the generation of an allelic series of subtle mutations at any locus of interest in the mouse.

The new field of chemical biology brings together chemists and biologists who are seeking to understand and mimic the natural world. One research strategy in this new field is the development of biologically active small molecules as molecular probes. This approach, which has been called 'chemical' genetics, has allowed elucidation of several pathways that have been difficult to study using traditional genetic approaches.

Computer simulation can be used to identify deleterious genes to be purged in breeding programs, especially for endangered species. Simulation compared continuous selfing, half-sib mating, and three mixtures of the previous two techniques as applied over 10 generations. Continuous selfing showed quick results, though without a high probability of extinction, and there were similar results for continuous half-sib mating. The most effective results used mild inbreeding.

Geneticists are working to eliminate problems that may result from using mice that have been bred for the absence of one gene. These techniques involve backcrossing the mutant with an inbred strain, a strategy that may not totally remove donor genes. The methods also suffer in their dependence on only two data points, whether presence or absence of a gene produces one effect, instead of having multiple basis for comparison. Meanwhile, experiments with mice lacking the gene for epidermal growth factor revealed multiple genotype interactions.

The activity of an alginate promoter of Pseudomonas aeruginosa was monitored by a reporter gene technology. Chromogenic and fluorogenic substrates from beta-galactosidase were used to demonstrate reporter activity. Fourier transform infrared spectroscopy, uronic acid accumulation and alginate- specific enzyme-linked immunosorbent assay measured the correlation between gene-up expression and alginate biosynthesis. The activation of the specific gene was demonstrated.

Optogenetics is emerging as a tool for studying the mammalian brain. Psychiatrist Karl Deisseroth and his colleagues have developed methods of injecting light-sensitive genes into brains to study certain behaviors.

New Corn Highly Resistant to Aflatoxin A new corn line from ARS is the best yet at naturally fending off aflatoxin, a fungal toxin that can be a threat to [...]

If you ask Warren Lamboy to send you Pinot Blanc budwood for plant breeding or other research, you can be sure you won't get a Melon instead--a grape called Melon, [...]

Superbly lean--but tender--beef rump roasts may reach more tables when new technology helps cattle breeders turn a possibly undesirable gene into a sure asset. On a genetic map for cattle, [...]

A marker system that can follow gene transfer in most arthropods and certain other phyla is described. Three vectors were constructed based on the Hermes, piggBac and mariner transposons, and were microinjected into Drosophila eggs. The transgenes appear to be stably integrated into the genome.

Two new methods for transferring yeast artificial chromosomes (YAC) into the germlines of mice could have several applications in the study of mouse genetics. The YAC transfer technology can be used to locate a particular gene in a large DNA fragment. Furthermore, the two methods have been found to have no effects on the DNA arrangement. However, the technique of direct microinjection was simpler than that involving spheroplast fusion.