Variable clinical presentations of patients with chromosomally detected deletions in the distal long arm (q) of chromosome 4 have been reported. The lack of molecular characterization of the deletion sizes and deleted genes hinders further genotype-phenotype correlation. Using a validated oligonucleotide array comparative genomic hybridization (oaCGH) analysis, we examined two patient with apparent chromosomal deletions in the distal 4q region. In the first, oaCGH identified a 2.441 megabase (Mb) duplication and a 12.651 Mb deletion at 4q34

We investigated the interaction of elevated CO2 and/or (Ozone) O3 on the occurrence and severity of aspen leaf rust (Melampsora medusae Thuem. f. sp. tremuloidae) on trembling aspen (Populus tremuloides Michx.). Furthermore, we examined the role of changes in leaf surface properties induced by elevated CO2 and/or O3 in this host–pathogen interaction. Three‐ to five‐fold increases in levels of rust infection index were found in 2 consecutive years following growing‐season‐long exposures with either O3 alone or CO2 + O3 depending on aspen clone. Examination of leaf surface properties (wax appearance, wax amount, wax chemical composition, leaf surface and wettability) suggested significant effects by O3 and CO2 + O3. We conclude that elevated O3 is altering aspen leaf surfaces in such a way that it is likely predisposing the plants to increased infection by aspen leaf rust.

We performed a pilot study to establish the analytical and clinical validity of whole genome oligonucleotide array comparative genomic hybridization (oaCGH) using the 44,000 oligonucleotide array from Agilent Technologies. DNA specimens from 10 patients with different chromosomal abnormalities were used as the test group and sex mismatched normal male or female DNA as references. A series of DNA mixtures containing 50%, 33%, and 25% of a known deletion was generated to evaluate the analytical capacity of oaCGH on detecting mosaic pattern. Receiver operating characteristic (ROC) curves were computed to evaluate sensitivity, specificity, and analytical resolution for detecting deletions, duplications, and mosaic patterns. The oaCGH detected the chromosomally recognized deletions, duplications, and additional genomic aberrations. Fluorescent in situ hybridization (FISH) assays using targeted BAC clone probes confirmed oaCGH findings. Failure in detecting marker chromosomes, a polymorphic inversion, and a Robertsonian translocation was also noted. The oaCGH achieved 99% sensitivity and 99% specificity with a resolution of 300-500 Kb. It also demonstrated 85% sensitivity and 95% specificity in detecting 50% mosaicism; however, increased test-to-test variations and reduced sensitivity were noted as the mosaic percentage decreased. Chromosome and oaCGH analyses on 50 pediatric patients with mental retardation (MR) and developmental delay (DD) delineated the genomic content of chromosomal abnormalities in nine cases, pathogenic genomic disorders in three cases and benign genomic variants in six cases. These results affirmed the analytical and clinical validity of oaCGH and prompted a cytogenomic algorithm to integrate oaCGH, chromosome and FISH analyses for genetic diagnosis.

To assess the clinical utility of genome-wide oligonucleotide arrays in diagnosis of mental retardation and to address issues relating to interpretation of copy number changes (CNCs), we collected results on a total of 1499 proband patients from five academic diagnostic laboratories where the same 44K array platform has been used. Three of the five laboratories achieved a diagnostic yield of 14% and the other two had a yield of 11 and 7%, respectively. Approximately 80% of the abnormal cases had a single segment deletion or duplication, whereas the remaining 20% had a compound genomic imbalance involving two or more DNA segments. Deletion of 16p11.2 is a common microdeletion syndrome associated with mental retardation. We classified pathogenic CNCs into six groups according to the structural changes. Our data have demonstrated that the 44K platform provides a reasonable resolution for clinical use and a size of 300 kb can be used as a practical cutoff for further investigations of the clinical relevance of a CNC detected with this platform. We have discussed in depth the issues associated with the clinical use of array CGH and provided guidance for interpretation, reporting, and counseling of test results based on our experience.