Characterization of 11p14-p12 deletion in WAGR syndrome by array CGH for identifying genes contributing to mental retardation and autism.

WAGR (Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation) syndrome is a rare genomic disorder caused by deletion of the 11p14-p12 chromosome region. The majority of WAGR patients have mental retardation and behavioral problems, and more than 20% of the patients also have features of autism. While the Wilms tumor/genitourinary anomalies and aniridia are caused by deletion of WT1 and PAX6 respectively, the genomic cause of mental retardation and autism in WAGR syndrome remains unknown. Using oligonucleotide arrays, we have characterized the 11p14-p12 deletions in 31 patients and identified all the genes involved in each deletion. The deletions had sizes ranging from 4.9 to 23 Mb that encompass 18-62 genes (40 on average). In addition to WT1 and PAX6, all the patients had deletion of PRRG4 (transmembrane gamma-carboxyglutamic acid protein 4). The majority of them had deletion of BDNF (brain-derived neurotrophic factor) and SLC1A2 [solute carrier family 1 (glial high affinity glutamate transporter) member 2]. Deletion of BDNF and SLC1A2 occurred in patients with autism more frequently than in those without autism. Literature review on the functions of the genes suggests that haploinsufficiency of SLC1A2, PRRG4, and BDNF may contribute to mental retardation and behavioral problems. In particular, BDNF may modulate the risk of autism in WAGR patients as suggested by its link with Rett syndrome as a target of MECP2. We observed that all the de novo deletions occurred in the chromosome 11 inherited from the father in the families genotyped, implying a predisposition for de novo mutations occurring in spermatogenesis and possible involvement of imprinting in cognitive impairment in WAGR patients.

Inflammation and iron deficiency in the hypoferremia of obesity.

CONTEXT: Obesity is associated with hypoferremia, but it is unclear if this condition is caused by insufficient iron stores or diminished iron availability related to inflammation-induced iron sequestration. OBJECTIVE: To examine the relationships between obesity, serum iron, measures of iron intake, iron stores and inflammation. We hypothesized that both inflammation-induced sequestration of iron and true iron deficiency were involved in the hypoferremia of obesity. DESIGN: Cross-sectional analysis of factors anticipated to affect serum iron. SETTING: Outpatient clinic visits. PATIENTS: Convenience sample of 234 obese and 172 non-obese adults. MAIN OUTCOME MEASURES: Relationships between serum iron, adiposity, and serum transferrin receptor, C-reactive protein, ferritin, and iron intake analyzed by analysis of covariance and multiple linear regression. RESULTS: Serum iron was lower (75.8+/-35.2 vs 86.5+/-34.2 g/dl, P=0.002), whereas transferrin receptor (22.6+/-7.1 vs 21.0+/-7.2 nmol/l, P=0.026), C-reactive protein (0.75+/-0.67 vs 0.34+/-0.67 mg/dl, P<0.0001) and ferritin (81.1+/-88.8 vs 57.6+/-88.7 microg/l, P=0.009) were higher in obese than non-obese subjects. Obese subjects had a higher prevalence of iron deficiency defined by serum iron (24.3%, confidence intervals (CI) 19.3-30.2 vs 15.7%, CI 11.0-21.9%, P=0.03) and transferrin receptor (26.9%, CI 21.6-33.0 vs 15.7%, CI 11.0-21.9%, P=0.0078) but not by ferritin (9.8%, CI 6.6-14.4 vs 9.3%, CI 5.7-14.7%, P=0.99). Transferrin receptor, ferritin and C-reactive protein contributed independently as predictors of serum iron. CONCLUSIONS: The hypoferremia of obesity appears to be explained both by true iron deficiency and by inflammatory-mediated functional iron deficiency.

Evaluation of an information retrieval system for assessment of toxicological effects of chemicals on fish, wildlife, and ecosystem components.

A user-oriented information retrieval system is needed for assessment of materials hazardous to fish, wildlife, food chain organisms, and other organisms essential to the maintenance to ecosystem processes and functions. Critical evaluation of data also requires rigorous documentation of test conditions, precision of methods used, and the sensitivity of the test organism. Particular emphasis of the evaluation was in developing practical criteria that aid in the use and interpretation of data with respect to need for further testing in a scoring exercise performed for the Toxic Substances Control Act Interagency Testing Committee. Recommendations are made for the integration of information on physical and chemical properties, health effects, ecotoxicology, and environmental concentration or exposure level.

Chemical control of the sea lamprey: the addition of a chemical to the environment.

Construction of the Welland Canal enabled shipping to by-pass Niagara Falls and enter the upper Great Lakes and also eliminated the barrier to the entry to the lakes by the sea lamprey (Petromyzon marinus Linnaeus). Within forty years the commercial fisheries of the Great Lakes was almost eliminated by this parasitic cyclostome. A search for selective chemical control of the sea lamprey was undertaken in the 1950's and culminated with the discovery of TFM (3-Trifluoromethyl-4-nitrophenol). At the request of the International Great Lakes Fishery Commission, the Bureau of Sport Fisheries and Wildlife undertook to assess the hazard of TFM to the aquatic ecosystem, to humans as well as to fish and wildlife. Studies were undertaken in Bureau laboratories as well as by contracts with university and private laboratories. Results of these studies to-date indicate that this material is not subject to biomagnification and does not pose a hazard to man or the the environment.