Microarrays and Microdeletions: Key Concepts Summarized
Learning Objectives and CME/Disclosure Information
This activity is intended for healthcare providers delivering care to women and their families.
After completing this activity, the participant should be better able to:
1. Relate the definition of a microdeletion 2. Discuss the differences between a CGH and SNP array
Estimated time to complete activity: 0.25 hours
Susan J. Gross, MD, FRCSC, FACOG, FACMG
President and CEO, The ObG Project
Disclosure of Conflicts of Interest
Postgraduate Institute for Medicine (PIM) requires faculty, planners, and others in control of educational content to disclose all their financial relationships with ineligible companies. All identified conflicts of interest (COI) are thoroughly vetted and mitigated according to PIM policy. PIM is committed to providing its learners with high quality accredited continuing education activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.
The PIM planners and others have nothing to disclose. The OBG Project planners and others have nothing to disclose.
Faculty: Susan J. Gross, MD, receives consulting fees from Cradle Genomics, and has financial interest in The ObG Project, Inc.
Planners and Managers: The PIM planners and managers, Trace Hutchison, PharmD, Samantha Mattiucci, PharmD, CHCP, Judi Smelker-Mitchek, MBA, MSN, RN, and Jan Schultz, MSN, RN, CHCP have nothing to disclose.
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Fees for participating and receiving CME credit for this activity are as posted on The ObG Project website. During the period from Dec 31 2017 through Jan 25 2023, participants must read the learning objectives and faculty disclosures and study the educational activity.
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Joint Accreditation Statement
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A microarray describes a newer technology that can identify small duplications or deletions of genetic material that previously could not be identified using conventional karyotyping alone. It has become a critical tool to help identify submicroscopic chromosomal deletions/duplications that underlie clinically significant syndromes in the prenatal period and throughout the lifespan.
What is a Deletion?
A deletion describes a chromosomal break where genetic material is lost
Credit: US National Library of Medicine
Deletions can be large or small, and can occur anywhere along a chromosome
Terminal deletion (end of a chromosome)
Interstitial (within the chromosome)
Duplication describes when additional material is gained
What is a Microdeletion?
Definition is based on size of missing DNA sequence
1Mb (megabase) = 1 million base pairs
Conventional karyotype is based on light microscopy and can usually only detect deletions > 5 Mb
Microdeletions refer to deletions smaller than those that can be seen on karyotype – i.e., < 5 Mb
What is a CNV (copy number variant)?
Deletions or duplications are ≥ 1 kb (1000 base pairs) to many hundreds of Kb in size
Small CNVs are common and found in 5 to 10% of individuals in the general population
Only 1 to 2% will have CNVs > 1Mb
Most CNVs are simply a part of normal human variation
If CNVs delete or add sufficiently large number of genes or result in a breakpoint within a gene, they may have significant clinical consequences
CGH vs SNP arrays
CGH (Comparative genome hybridization)
The array is constructed with single short DNA sequences from the regions of interest
‘Test’ and ‘control’ DNA are labelled with different fluorescent colors and then hybridized (annealed) to complementary sequences of interest on the array
The relative amounts of test vs control DNA can be measured
Excess control DNA signal color signifies a deletion in the test sample
Excess test DNA signal color signifies duplication in the test sample
The array is constructed with short DNA sequences
Each region of interest will have two DNA sequences, representing the two possible alleles (versions) of known SNPs
Only ‘test DNA’ is labelled and hybridized to the allele specific probes within the array
Relative intensity of the hybridization signal is used to detect if DNA sequence is deleted or duplicated
Low/absent intensity signal signifies deletion
Excess signal signifies duplication
Additional capabilities of SNP array compared to CGH
Can detect triploidy, maternal cell contamination and mosacism
Can detect consanguinity and uniparental disomy (UPD) which can be associated with genetic syndromes
Rather than having one copy of each SNP allele, a region of identical SNPs, known as absence of heterozygosity (AOH), will be apparent
Labs may report AOH, raising concern for
Autosomal recessive disorders related to genes in that particular sequence or
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This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
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presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
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