high yield cytogenetics non disease concepts

three types of chromosomes based on centromere position?

 Metacentric (arms similar), Submetacentric (P shorter than Q), Acrocentric (P essentially absent).

Which chromosomes are acrocentric and why are they important?

Chromosomes 13, 14, 15, 21, 22; their P arms contain satellite DNA (can be lost without effect) and are involved in Robertsonian translocations.

What do the following symbols mean in chromosome nomenclature: +, -, del, dup, t, inv, iso, mos, r, rob?

+ = gain, - = loss, del = deletion, dup = duplication, t = translocation, inv = inversion, iso = isochromosome, mos = mosaic, r = ring, rob = Robertsonian translocation

What do “mat,” “pat,” and “DM” mean in chromosome nomenclature?

mat = maternal origin, pat = paternal origin, DM = de novo abnormality.

What is G-banding and what does it show?

Chromosome staining technique; AT-rich regions stain dark, GC-rich stain light.

What is high-resolution banding and when is it performed?

Banding done in prophase/early metaphase; reveals more subtle abnormalities (up to 850 bands vs. 400).

 What is FISH and when is it useful?

Fluorescent probes highlight specific regions/chromosomes; rapid, targeted, good for aneuploidies

What is a microarray (array CGH) and what can it detect?

Compares patient DNA vs. control to find deletions/duplications genome-wide at high resolution.

What is SNP microarray’s advantage over array CGH?

Detects deletions/duplications plus Regions of Homozygosity (ROH), suggesting consanguinity or recessive risk.

What is a key limitation of microarray?

Cannot detect balanced rearrangements or translocations.

What are incidental findings in genetic testing?

Unexpected results, like unrelated conditions or evidence of parental consanguinity

What is Uniparental Disomy (UPD)?

 Both copies of a chromosome inherited from one parent, often due to trisomy rescue.

What is the difference between isodisomy and heterodisomy?

Isodisomy = identical copies (↑ recessive disease risk). Heterodisomy = two different copies (linked to maternal age nondisjunction)

What are telomeres and subtelomeric regions?

Telomeres = protective caps/biological clock; subtelomeric regions = gene-rich, deletions cause ~5% of unexplained intellectual disability.

What are ring chromosomes, and why are they unstable?

Formed by end deletions that reattach in a ring; unstable, often mosaic, associated with conditions like Turner syndrome.

What is the difference between paracentric and pericentric inversions?

Paracentric = inversion without centromere (unbalanced gametes inviable). Pericentric = inversion includes centromere (can produce viable unbalanced gametes)

 What is an isochromosome?

A chromosome with two identical arms (e.g., two Q arms), caused by horizontal centromere division.

What is mosaicism?

 Presence of two or more genetically distinct cell lines in one person due to post-zygotic errors.

What is the difference between euploidy and aneuploidy?

Euploidy = complete sets/multiples of 23 (haploid, diploid, triploid). Aneuploidy = extra/missing individual chromosome (e.g., trisomy, monosomy).

What is nondisjunction, and what does it cause?

Failure of chromosomes to separate during meiosis; main cause of aneuploidies

What is the maternal age effect?

Risk of nondisjunction and aneuploidies increases with maternal age, especially after 35

How does cancer cytogenetics differ from inherited cytogenetics?

Cancer abnormalities are somatic (tumor-specific) and can be diagnostic/prognostic, e.g., Philadelphia chromosome in CML.