The yeast Candida albicans is the major pathogen causing human fungal infections. C. albicans is not amenable to functional genomic strategies used for other micro-organisms, because of mating difficulties, its diploid nature and the lack of random insertional mutagenesis methods.In March Nature Biotechnology Marianne De Backer and colleagues describe an approach to overcoming these limitations, in order to perform a genome-wide screen for gene function (Nature Biotechnology 2001, 19:235-241). T

Homozygous mutant cells can be generated from embryonic stem (ES) cells with a single insertion of a drug-resistance marker by increasing the concentration of the selection drug. In the March Nature Genetics, Lefebvre et al. report analysis of the mechanism governing this loss of heterozygosity (LOH) (Nature Genetics 2001, 27:257-258). They used an ES cell line resulting from a cross between two different inbred mouse 129 substrains which could be distinguished by single sequence-length polymorp

In the March Nature Genetics, Gopal et al. describe a two-step approach to identify novel genes by combining stringent annotation with broad gene-prediction techniques (Nature Genetics 2001, 27:337-340). The first step involves identification of potential exons using the GENSCAN gene-finding program. In the second step, predicted genes are compared with all available gene and protein sequences, including expressed sequence tags (ESTs) from other organisms, at the protein level (in all six transl

Mice lacking telomerase exhibit reduced fertility and severe developmental defects after a few generations. In the March 2 Science, Riha et al. report the effects of telomere shortening in Arabidopsis thaliana (Science 2001, 291:1797-1800). Homozygous telomerase-deficient plants displayed progressive telomere shortening (250-500 base pairs per generation). Defects in vegetative organs and reproductive systems did not appear before the sixth generation (reduced leaf size and symmetry), however. T

Early detection is critical for the clinical management of breast cancer. In the February 27 Proceedings of the National Academy of Science, Martin et al. describe a highly sensitive blood-based assay to detect and classify solid tumours (Proc Natl Acad Sci USA 2001, 98:2646-2651). The high-throughput assay involves a two-step approach, combining differential display with cDNA microarrays. Martin et al. analysed blood samples from 26 breast cancer patients for the expression of 12 breast can

DiGeorge syndrome (DGS; also known as Velo-cardio-facial syndrome) is associated with hemizygous deletion of a region of human chromosome 22q11, causing a range of abnormalities including cardiovascular defects, hypoplasia of the thymus and parathyroid gland, and craniofacial abnormalities.Three research groups have identified the TBX1 gene, a member of the T-box family of transcription factors, as a key determinant of the DGS phenotype. Merscher et al. (Cell 2001, 104:619-629) and Lindsay et al

B lymphocytes that produce antibodies recognizing self antigens are tolerized by a process of clonal selection, which involves clonal deletion, anergy and a gene-recombination event called receptor editing. In the February 23 Science, Casellas et al. describe a model mouse system for investigating the importance of receptor editing (Science 2001, 291:1541-1544). They generated a polymorphic immunoglobulin kappa allele by replacing the mouse kappa constant (mCkappa) region with the human sequenc

Leprosy, which has been described since biblical times, is caused by the obligate intracellular pathogen Mycobacterium leprae. In the February 22 Nature, Cole et al. report the sequencing of the entire M. leprae genome (Nature 2001, 409:1007-1011). Pairwise comparison with the genome sequence of the closely related M. tuberculosis revealed that the M. leprae genome has undergone considerable reduction during evolution. The 3.27 megabase M. leprae genome contains less than half the number of g

The identification of alleles associated with complex hearing defects, such as presbyacusis (age-related hearing loss, AHL), presents a formidable challenge to geneticists. In the February Nature Genetics Johnson et al. describe their use of elegant mouse breeding experiments to identify the first example of a mitochondrial DNA (mtDNA) mutation that acts as a modifier of a nuclear AHL locus (Nat Genet 2001, 27:191-194). They performed a series of reciprocal backcrosses between three hearing-impa

Cloning and in vitro culture of sheep embryos have been associated with bigger livestock and 'large offspring syndrome' (LOS). In the February Nature Genetics Young et al. provide a molecular explanation for the observed fetal overgrowth (Nat Genet 2001, 27:153-154). They developed a culture system that consistently results in large offspring (LO) in 25% of births. Young et al. measured the levels of several imprinted genes that are associated with fetal overgrowth syndromes in man. The levels o

II restriction enzyme reveals an unusual scissor-like motion that allows DNA entry.

Observations in a mouse model of diabetes have led to the discovery of a human susceptibility locus.