Microarray
Introduction to chromosomal microarray analysis (CMA)
Technical standards and guidelines
Helpful resources for SNP Microarray interpretation
Classification of constitutional copy number variants
Useful databases and online resources
Interpreting regions of homozygosity
Introduction to chromosomal microarray analysis (CMA)
Introduction to Chromosomal Microarray Analysis
This short presentation provides an introduction to how CMA works, different types of array technology and probes, and assay strengths/limitations.
Technical standards and guidelines
ACMG technical standards to assist labs with CMA validation.
Shao et al. 2021 (PMID: 34131312)
Helpful Resources for SNP microarray interpretation
Interpretation of SNP microarrays resources
This document provides some background and a description of some helpful resources for interpretation of SNP microarrays.
Rowsey, Znoyko, and Wolff Whole-Genome Single Nucleotide Polymorphism Microarray for Copy Number and Loss of Heterozygosity Analysis in Tumors. Methods Mol Biol 2019:1908:89-111. (PMID:30649723)
Conlin et al. Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis. Hum Mol Genet 2010 Apr 1;19(7):1263-75 (PMID: 20053666)
Genome-Wide Mosaicism, Chimerism, and Contamination: Recognizing and Interpreting Genotyping Pattern
Presentation from Dr. Laura Conlin at the Cancer Genomics Consortium 2018 Annual Meeting
SNP Interpretation guide (Greenwood Genetic Center)
Classification of copy number variants
ACMG/ClinGen guideline for interpretation and reporting of CNVs
- Overview: ACMG Recommendations for CNV Curation
- Riggs et al. 2020 (PMID: 31690835)
- ClinGen CNV Interpretation Calculator - online tool based on Riggs et al. guideline
- ClinGen CNV Technical Standards Web Series - a series of webinars describing the guidelines and going over helpful resources/examples.
Useful databases and online resources for CNV analysis
CNVs in healthy populations (i.e. controls)
- Database of Genomic Variants (DGV)
- dbVar (NCBI database of structural variation)
- gnomAD SV (The Genome Aggregation Database)
This document provides more information on how to search structural variants in gnomAD
CNVs in Human Disease (i.e. Cases)
- ClinVar
- DECIPHER
- OMIM - An online catalog of human genes and genetic disorders
- PubMed
- The Human Gene Mutation Database (HGMD)
- Optimizing UCSC Browser settings
- Useful keyboard shortcuts: h+m highlights the region you are currently viewing (h+c removes the highlighting)
- Custom tracks: can upload BED files for regions of interest
- Genome build conversion: LiftOver tool
- Includes manually curated dosage sensitive regions/genes
- Curations of recurrent CNV - table view of recurrent microdeletions/duplications, including genomic coordinates, haploinsufficiency/triplosensitivity predictions, and date CNV was last evaluated by ClinGen. Click on an individual CNV to see more details including references.
- Dosage Sensitivity Recurrent CNV BED file can be downloaded from ClinGen website and then uploaded as a custom track in UCSC or in your array analysis software. Useful for identifying recurrent CNV as well as distinguishing breakpoints (e.g. typical vs. distal 22q deletions).
- A tool linked with OMIM to identify disease genes within a chromosomal region
- Enter genomic coordinates and then filter to show OMIM disease genes, dominant/recessive inheritance, or using phenotype terms
- Useful for identifying recessive genes within a homozygous region
- YouTube video linked on homepage provides more details on how to use
Predictors of gene dosage sensitivity
- LOEUF / pLI (gnomAD)
- pHaplo / pTriplo (DECIPHER)
- Dosage sensitivity (HI/TS) scores (ClinGen)
Interpreting regions of homozygosity
Gonzalez et al. 2022 (PMID: 34906464)
ACMG technical standards for interpretation and reporting of large regions of homozygosity and suspected consanguinity/uniparental disomy, 2021 revision
Del Gaudio et al. 2020 (PMID: 32296163)
- Points to consider from ACMG in diagnosis of UPD
- Includes description of common mechanisms leading to UPD, chromosomes of interest, and follow-up testing which may be required after CMA
Somatic CMA Resources
Classification guidelines
ACMG/CGC technical laboratory standards for interpreting and reporting acquired copy number abnormalities and copy-neutral loss of heterozygosity
Mikhail et al. 2019 (PMID: 31138931)
CGC Gene Lists
Gene lists produced by CGC working groups
- Includes genes of interest for different tumor types
- Includes AED and BED files available for download, which can be uploaded into your array interpretation software
Cancer Genomics Resources
Clinical/pathology background
- WHO Blue Books
- National Comprehensive Cancer Network (NCCN) Guidelines
Evaluating significance of chromosome abnormalities
- Compendium of Cancer Genome Aberrations (CCGA)
- Atlas of Genetics and Cytogenetics in Oncology and Haematology
- Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer
For more information about how and when to use these and other resources, check out this page of Cancer Genomics Resources.
Data and information obtained from the Cancer Genomics Consortium (CGC) and the Geneticist Toolkit are provided as an educational resource only; they should not be used as a stand-alone resource for clinical decision making or reporting, as they may contain errors or omissions. Review of the data by an appropriately trained medical professional is required for clinical reporting. Some of these resource pages may include links to content created by commercial entities and/or which require a fee for service; the inclusion of such material is meant for educational purposes only and does not represent an endorsement of these entities by the CGC.
The CGC and all participating entities make no representation or warranty, express or implied, including without limitation any warranties of merchantability or fitness for a particular purpose or warranties as to the identity or ownership of data or information, the quality, accuracy or completeness of data or information, or that the use of such data or information will not infringe any patent, intellectual property or proprietary rights of any party. The CGC shall not be liable for any claim for any and all loss, harm, illness or other damage or injury arising from access to or use of data or information howsoever caused, including without limitation, any direct, indirect, incidental, exemplary, special or consequential damages, even if advised of the possibility of such damages. The data and information obtained from the Geneticist Toolkit shall not be used as a substitute for the user's skills, expertise and experience.
