Search

Variation is essential to ecological and evolutionary dynamics, but genetic variation of quantitative traits may be concentrated in a limited number of dimensions, constraining ecoevolutionary dynamics. We describe high-dimension variation in natural accessions of the model alga, Chlamydomonas reinhardtii, and test the hypothesis that extensive fitness variation across 30 environments is constrained to a small number of axes., We used high-throughput phenotyping to investigate morphological, fitness, and genotype × environment (G × E) variation in 18 natural C. reinhardtii accessions in 30 environments., The organismal phenotypes of cell cycle, cell size, and phototactic behavior exhibited substantial genetic variation between lines, and we found up to 74-fold fitness variation across accessions and environments. Approximately 47% of the extensive G × E variation is accounted for by the first two principal components (PCs) of the G-matrix corresponding to covariation in metals response, nitrogen availability, or salt and nutrient response., The natural variation of C. reinhardtii accessions supports the hypothesis that, despite abundant genetic variation across single environments, the species' adaptive response should be constrained along few major axes of selection. These results highlight the utility of natural accessions for integrating ecoevolutionary and genetic research. [ABSTRACT FROM AUTHOR]

Arabidopsis thaliana , like many species, is characterized by abundant genetic variation. This variation is rapidly being cataloged at the sequence level, but careful dissection of genetic variation in whole-organism responses to stresses encountered in the natural environment are lacking; this functional variation can be exploited as a natural mutant screen to determine gene function. Here, we document physiological and transcriptomic response to soil drying in 17 natural accessions of Arabidopsis. By imposing ecologically realistic stress conditions, we found that acclimation in Arabidopsis involved a strong signature of increased investment in photosynthesis, carbohydrate turnover, and root growth. Our results extend previous work in the Columbia accession suggesting that abscisic acid signaling pathways play an important role in drought stress response. We also identified several mechanisms, including an increase in leaf nitrogen concentration and upregulation of two-component signaling relays, that were common to most natural accessions but had not been identified in studies using only the Columbia accession. Principal component analysis reveals strong correlations between suites of genes and specific physiological responses to stress. The functional variants we identified may represent adaptive mutations in natural habitats and useful variants for agronomic improvement of crop species. [ABSTRACT FROM AUTHOR]

The ATM gene is mutated in ataxia-telangiectasia (AT). Heterozygote female relatives of AT cases have a 2-7fold increased risk of breast cancer. We previously reported high risks of breast cancer associated with certain ATM variants. To estimate the risks more precisely, we have examined two ATM variants, c.1066-6T>G (IVS10-6T>G) and c.4258C>T (p.Leu1420Phe), in additional cases and controls from the same Australian cohorts previously used to estimate the risk of breast cancer associated with c.1066-6T>G. A total of 775 and 84 population-based controls were genotyped for the c.1066-6T>G and c.4258C>T ATM variants respectively, as were index cases from 378 and 373 non- BRCA1/2 breast cancer families. Penetrance was estimated by Bayes factor analysis. The allele frequencies of ATM c.1066-6T>G and c.4258C>T estimated from controls were 0.005 (95% CI=0.002 to 0.009) and 0.012 (95% CI=0.001 to 0.042), respectively. We identified three new breast cancer families with c.1066-6T>G, and seven families with c.4258C>T. Combining with the two c.1066-6T>G families previously reported, the estimated penetrance to age 70 of c.1066-6T>G was 17.2% (95% CI=4.7% to 37.5%). For c.4258C>T, the estimated average penetrance was 4.8% (95% CI 1.7% to 10.1%). In conclusion, we found no evidence that the ATM c.4258C>T variant increases breast cancer risk, and little evidence that c.1066-6T>G confers an elevated risk. Analysis of additional families will be necessary to define more precisely the risk, if any, associated with c.1066-6T>G. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

This study addresses the prevalence of ATM mutations and the association with breast cancer in Austrian families selected for a history of breast or ovarian cancer or both [hereditary breast and ovarian cancer (HBOC)]. In 270 HBOC families previously screened for BRCA1 and BRCA2 mutations, 137 different sequence alterations of ATM were identified. Seven of these were mutations presumed to cause ataxia telangiectasia based on their effect on the ATM protein, including five that caused a protein truncation and two missense mutations in the catalytic kinase domain of the highly conserved COOH terminus of the protein. The seven mutations were found in 10 families (3.7%). In addition, one missense variant, L1420F, was observed in 13 HBOC families (4.8%) but was not observed in any of the 122 healthy volunteers with no history of breast cancer. In addition, the variant segregated with breast cancer in some of the families, suggesting that it may be pathogenic for breast cancer. Sixty-two additional variants of potential significance were observed in 65 HBOC families, but not in healthy controls. These variants included 24 sequence alterations with possible effects on splicing or protein-protein interactions. This study indicates that there is a significant prevalence of ATM mutations in breast and ovarian cancer families and adds to a growing body of evidence that ATM mutations confer increased susceptibility to breast cancer.