Large-scale copy number variants (CNVs): Distribution in normal subjects and FISH/real-time qPCR analysis
Bibliographic record
Abstract
BACKGROUND: Genomic copy number variants (CNVs) involving >1 kb of DNA have recently been found to be widely distributed throughout the human genome. They represent a newly recognized form of DNA variation in normal populations, discovered through screening of the human genome using high-throughput and high resolution methods such as array comparative genomic hybridization (array-CGH). In order to understand their potential significance and to facilitate interpretation of array-CGH findings in constitutional disorders and cancers, we studied 27 normal individuals (9 Caucasian; 9 African American; 9 Hispanic) using commercially available 1 Mb resolution BAC array (Spectral Genomics). A selection of CNVs was further analyzed by FISH and real-time quantitative PCR (RT-qPCR). RESULTS: A total of 42 different CNVs were detected in 27 normal subjects. Sixteen (38%) were not previously reported. Thirteen of the 42 CNVs (31%) contained 28 genes listed in OMIM. FISH analysis of 6 CNVs (4 previously reported and 2 novel CNVs) in normal subjects resulted in the confirmation of copy number changes for 1 of 2 novel CNVs and 2 of 4 known CNVs. Three CNVs tested by FISH were further validated by RT-qPCR and comparable data were obtained. This included the lack of copy number change by both RT-qPCR and FISH for clone RP11-100C24, one of the most common known copy number variants, as well as confirmation of deletions for clones RP11-89M16 and RP5-1011O17. CONCLUSION: We have described 16 novel CNVs in 27 individuals. Further study of a small selection of CNVs indicated concordant and discordant array vs. FISH/RT-qPCR results. Although a large number of CNVs has been reported to date, quantification using independent methods and detailed cellular and/or molecular assessment has been performed on a very small number of CNVs. This information is, however, very much needed as it is currently common practice to consider CNVs reported in normal subjects as benign changes when detected in individuals affected with a variety of developmental disorders.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".