ABMGG Cytogenetics and Chromosomal Analysis 2 — Questions and Answers
Question 1: The Philadelphia chromosome, found in chronic myelogenous leukemia (CML), results from which chromosomal rearrangement?
- Inversion of chromosome 9
- Deletion of chromosome 22q
- Reciprocal translocation t(9;22)(q34;q11.2) (Correct answer)
- Trisomy 9
Correct answer: Reciprocal translocation t(9;22)(q34;q11.2)
The Philadelphia chromosome is formed by t(9;22)(q34;q11.2), which fuses BCR on chromosome 22 with ABL1 on chromosome 9 to create the oncogenic BCR::ABL1 fusion gene.
Question 2: A pericentric inversion involves a chromosomal segment that:
- Does not include the centromere
- Spans the centromere, including both arms (Correct answer)
- Involves only the short arm
- Results in a ring chromosome
Correct answer: Spans the centromere, including both arms
A pericentric inversion includes the centromere, with breakpoints in both the short (p) and long (q) arms, potentially changing the chromosome's arm ratio.
Question 3: A carrier of a balanced reciprocal translocation is at risk of producing offspring with which abnormality?
- Only normal offspring
- Offspring with unbalanced chromosomal segments causing partial monosomy or trisomy (Correct answer)
- Only monosomic offspring
- Offspring with whole-chromosome aneuploidy
Correct answer: Offspring with unbalanced chromosomal segments causing partial monosomy or trisomy
During meiosis, a balanced translocation carrier can produce unbalanced gametes through 3:1 or 2:2 segregation, resulting in offspring with partial monosomy or partial trisomy.
Question 4: Chromosomal mosaicism in a patient is BEST defined as:
- Two different chromosomal structural variants in the same cell
- The presence of two or more cytogenetically distinct cell lines from the same zygote (Correct answer)
- A heterozygous deletion detectable by FISH
- Copy number variation between maternal and paternal alleles
Correct answer: The presence of two or more cytogenetically distinct cell lines from the same zygote
Mosaicism is the coexistence of two or more cell populations with different chromosomal constitutions arising from a single zygote, typically due to a post-zygotic mitotic error.
Question 5: Uniparental disomy (UPD) can cause disease even when both copies of a chromosome are structurally normal primarily because of:
- Dosage imbalance from two copies of one chromosome
- Genomic imprinting causing silencing of maternally or paternally imprinted genes (Correct answer)
- Increased recombination frequency
- Loss of heterozygosity for oncogenes
Correct answer: Genomic imprinting causing silencing of maternally or paternally imprinted genes
Genomic imprinting silences certain genes depending on parental origin; UPD can result in either two silenced (imprinted) copies or two expressed copies, disrupting normal gene dosage for imprinted loci.
Question 6: Array comparative genomic hybridization (aCGH) detects copy number variants (CNVs) by comparing:
- Patient DNA methylation to a reference panel
- Hybridization intensity of patient DNA vs. a reference DNA on oligonucleotide probes (Correct answer)
- Patient RNA expression levels to normal tissue
- Sequence reads from patient DNA to a reference genome
Correct answer: Hybridization intensity of patient DNA vs. a reference DNA on oligonucleotide probes
In aCGH, differentially labeled patient and reference DNAs are co-hybridized to probes on a microarray; the ratio of fluorescence intensities reveals gains (duplications) or losses (deletions) in the patient.
Question 7: Spectral karyotyping (SKY) and multicolor FISH (M-FISH) are especially useful for identifying:
- Point mutations within a gene
- Complex chromosomal rearrangements and marker chromosomes of unknown origin (Correct answer)
- Repeat expansion disorders
- SNP-level variants
Correct answer: Complex chromosomal rearrangements and marker chromosomes of unknown origin
SKY/M-FISH uses combinatorial labeling with multiple fluorochromes to paint each chromosome a unique color, making it ideal for characterizing complex rearrangements and small marker chromosomes.
ABMGG Cytogenetics and Chromosomal Analysis 2
The Philadelphia chromosome, found in chronic myelogenous leukemia (CML), results from which chromosomal rearrangement?