Cytogenetics Flashcards
If someone has leukemia what is the issue with genetic testing? Can you use a blood sample?
No, because you will get the somatic mutations from the cancer in the blood sample. We are looking for germline changes in genetic testing. We can get somatic mutations from the blood in the sample.
Define hemizygous.
In the special case in which an XY male has a variant allele for a gene located on the X chromosome, they are referred to as hemizygous. Thi sis because they only have one X, so this allele wouldn’t be considered heterozygous or homozygous.
hemi = half
Define heterozygous
When two different sets of alleles are present at a locus, a person is heterozygous, or a heterozygote.
What is a compound heterozygote?
When two different sets of alleles are present at a locus, a person is heterozygous, or a heterozygote. The term compound heterozygote is used to describe a genotype in which two different variants from a reference sequence are present, rather than one wild-type and one variant allele.
Define homozygote.
When a person has a pair of identical alleles at a locus encoded in nuclear DNA, they are said to be homozygous, or a homozygote. When the combination of alleles matches to the human reference genome it is referred to as homozygous wild-type
DiGeorge - make a slide about this syndrome - these are symptoms Dr. Talls went over in class. He said we should know this syndrome well.
developmental delay
cleft
congenital heart defects
What is a copy number variant?
Copy number variant (CNV) An unbalanced variation in DNA sequence defined by the loss or addition of a segment of DNA, typically defined as larger than 1kb and ranging up to 3Mb. CNVs may be alleles that are tandem replications involving two or more copies of a DNA segment. aka structural variant.
Why is it important to do genetic testing for aneuploidies even though they aren’t inherited?
Because it could be caused by translocations. Balanced translocations in parent that could cause issue for child.
When we are ordering genetic testing is ordering a sequence technique enough?
No, we should always check for CNVs as well in order to know how many copies of the gene there are. If the whole gene is deleted I don’t think sequencing will even notice that.
Compare sequencing and CNV analysis.
Sequencing is checking for changes in nucleic acids (like misspells).
CNV analysis is checking for how many copies there are of a gene or chromsome - we usually expect 2 copies
sequencing => correctness/accuracy
CNV => amount/dosage/amplitude
CNV is looking for deletions/duplications (1 copy = deletion, 3 copies = duplication)
Examples of CNV analysis methods and what they are doing
karyotype, FISH, CMA
these types of tests do NOT look at nucleic acids for misspellings, but they can tell us if a gene is completley missing
CNV = copy number variations
What are the names of the tests avaiable for CNV analysis?
- karyotype = chromsome analysis
- chromsomal microarray (CMA) = genome wide copy number analysis
- Florescence in Situ Hybridization (FISH) = used for somatic testing (ex: cancer) more often than for germline testing
- Multiplex Ligation-Dependent Probe Amplification (MLPA) = multiplex PCR (we don’t use this)
- Whole genome Sequencing (WGS)
Clinical Indications for CNV analysis?
unless there is a definite non-chromosomal diagnosis (ex: known SNV ), genomic analysis should be considered to detect copy number variants. CNV analysis should always complement sequencing technique
SNV = single nucleotide variant
What are some problems with early growth and development that would be clinical indications for CNV analysis?
- failure to thrive, short stature
- developmental delays/intellectual disability/Autism Spectrum Disease
- dysmorphic features
- multiple congenital anomalies
- ambiguous genitalia
What is usually the first tier option for CNV analysis?
CMA
