Term
| Microarray (CMA -- Chromosomal Microarray) |
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Definition
| Looks for any copy number variant that isn’t 2 (the usual 1 from mom and 1 from dad). |
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Term
| Array CGH (comparative genomic hybridization) |
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Definition
A type of microarray that compares test samples to a control sample.
Think of it like “reverse FISH.” Many probes are attached to an array. Crush up DNA, fluoresce it with a certain color (green), and wash over array so the pieces stick. Then measure the amount of fluorescence.
In Array CGH, do the same thing but add a different color (red) fluorescence to the control DNA. If the control and the patient have the same amount, the spot will be yellow.
More red means more control DNA and more green means more patient DNA. Most labs aren't doing this as much -- more SNP based. |
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Term
| Single Nucleotide Polymorphism (SNP) based Array |
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Definition
Generate probes (much smaller proves than in Array CGH) about 25-50 bp. Labs have taken a bunch of controls, run microarray, and made an average of the fluorescence that they should see.
Then they run the patient’s DNA over the microarray with the smaller SNP based probes and compare the amount of fluorescence to the controls.
Because you have smaller probes you can put more one one chip -- one has 2.7 million. |
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Term
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Definition
SNP based arrays have become more advanced, though they still work basically the same. Now, however, they generate probes for both possibilities (A or T, G or C).
Therefore, the array can give you genotypic information. It can tell you if there is a lot of homozygosity, and therefore probable consanguinity. |
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Term
| Single Nucleotide Polymorphism |
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Definition
| A single base pair difference. Mostly found in genes or introns. They can affect the function of a gene, but they do not typically affect health or development. |
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Term
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Definition
Not done much in a clinical basis, mostly research. Probes are made of cDNA (or complementary DNA) matched to the mRNA of known genes.
Therefore, by looking at the mRNA made you can create a gene expression array. The amount of fluorescence that each probe shows determines the expression level of the gene.
This is useful in cancer specimens, to see if the tumor expresses genes that will make it respond well to a drug. |
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Term
| 22q11.2 / DiGeorge / VCF syndrome |
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Definition
Most common recurrent microdeletion.
Clinical characteristics include cardiac defects, cleft palates, thymus hypo or aplasia, parathyroid hypo or aplasia, characteristic facies, and developmental delays.
Occurs frequently because of low copy repeats (segmental duplications) -- regions of repeated DNA. This causes chromosomes to not line up properly -- if crossover occurs when they are not aligned there will be a deletion or a duplication. |
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Term
| Unmasking a recessive disorder |
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Definition
Sometimes someone can inherit a harmless deletion from one parent and a recessive gene from the other, giving them a recessive condition.
To determine this you must “unmask” the recessive disorder. Do a microarray to find the deletion. Look for the point mutations that might exist on the other chromosome or in the parents. |
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Term
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Definition
An x-linked condition that causes:
Congenital cataracts
Screwdriver-shaped incisors
Ear abnormalities
30% intellectual disability |
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Term
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Definition
An autosomal recessive syndrome that causes:
- “Molar sign” in the brain
- Renal and liver abnormalities
This is due to abnormal cilia |
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Term
| Area of homozygosity/absence of heterozygosity |
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Definition
At a certain genetic location you have the same exact sequence for both alleles. This can happen if parents are related to each other.
There are tools to analyze how many “rounds of homozygosity” or “ROH” people have. It can cause recessive conditions. |
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Term
| Newer microdeletion syndromes |
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Definition
New microdeletion syndromes are being quickly discovered. Often they include autism or developmental delays.
They have variable phenotypes and inheritance patterns.
They also have reduced penetrance and variable expressivity (parents may have same microdeletion).
This made them harder to pick up and classify phenotypically. |
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Term
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Definition
| A newer microdeletion syndrome that causes DD, ID, hypotonia, seizures, dysmorphic features, and friendly behaviour with frequent laughing. |
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Term
| What is the most common cause of microdeletions? |
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Definition
LCRs, Low Copy Repeats, also called segmental duplications.
These are areas of the chromosome that have duplicated material. Therefore, they are more apt to line up wrong when crossing over, causing microdeletions and duplications. |
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Term
| You find a microdeletion with an abnormal phenotype. What, other than the microdeletion, could also be causing the phenotype? |
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Definition
1. Imprinting (you might need a copy from mom and dad, and have a phenotype because you have just one or the other)
2. Unmasking a recessive condition (You might have a recessive allele on one side, a deletion on the other)
3. Modifier of a phenotype (Your microdeletion might have cut out a genetic modifier, making the condition worse) |
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