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Microarrays and Microdeletions: Key Concepts Summarized


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.

Key Concepts

What is a Deletion?

  • A deletion describes a chromosomal break where genetic material is lost
Genetic Deletion

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

Key Points:

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

SNP array

  • 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
      • UPD, depending on chromosome and region

Learn More – Primary Sources:

ACOG Committee Opinion 682: Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology

The use of chromosomal microarray for prenatal diagnosis

ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013

Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Practice guideline: joint CCMG-SOGC recommendations for the use of chromosomal microarray analysis for prenatal diagnosis and assessment of fetal loss in Canada