Cytogenetics

What is the purpose of cytogenetic banding techniques?

To create chromosome-specific banding patterns (chromosome fingerprints) that allow detection of abnormalities such as deletions, duplications, or rearrangements.

Why are mitotic cells commonly used in cytogenetic studies?

Because they are easy to obtain and chromosomes can be visualized at metaphase.

Which human cells are typically cultured for chromosome studies?

Leukocytes (white blood cells).

What is the most widely used stain for chromosome banding?

Giemsa stain (a mix of methylene blue, eosin, and azure B).

What do dark G-bands represent?

Heterochromatin: densely packed, genetically inactive regions.

What do light G-bands represent?

Euchromatin: less condensed, transcriptionally active regions.

How many bands are typically resolved in low vs. high resolution banding?

About 400 bands per haploid set in low resolution, ~850 bands per haploid set in high resolution.

Where is the CFTR gene located?

Chromosome 7, long arm, G-band 31.2 (7q31.2).

What is ploidy?

The number of complete sets of chromosomes in a cell.

What does euploid mean?

Having a complete set of chromosomes (e.g., diploid = 2n, triploid = 3n).

What is polyploidy?

Having more than two complete sets of chromosomes.

Give four examples of polyploidy in plants.

Dandelion (3n, asexual), Banana (3n, sterile), Cotton (4n), Wheat (6n).

How common is polyploidy in animals?

Rare; found in some fish (salmon, goldfish), lizards, and inverts. Only one mammal: Argentinian rat (4n=102).

tissue-specific polyploidy

When cells replicate chromosomes and nuclei without cytokinesis, producing polyploid nuclei.

Which human tissues commonly show polyploidy?

Liver and kidney cells (often tetraploid, 4n=92).

What is aneuploidy?

The under- or over-representation of a single chromosome or chromosome segment.

(e.g., 2n+1 = trisomy, 2n–1 = monosomy).

Aneuploidy implies genetic imbalance, polyploid does not.

Aneuploidy occurs because of nondisjunction in meiosis

How does aneuploidy differ from polyploidy?

Aneuploidy = imbalance in specific chromosomes; polyploidy = extra whole sets of chromosomes.

What is trisomy?

Presence of three copies of one chromosome (2n+1).

What is monosomy?

Presence of only one copy of a chromosome (2n–1).

Ex: Turner Syndrome = only one sex chromosome

What is the main cause of aneuploidy?

Nondisjunction during meiosis.

What happens in nondisjunction during meiosis I?

Chromosomes pulled to same side:
— All four gametes produced are unbalanced

— 2 are +1, 2 are -1

ex: 21, 21, 19, 19

What happens in nondisjunction during meiosis II?

Sister chromatids go to same side:

— only two of the four gamtes are unbalances

— 1 is +1, 1 is -1, the other 2 are normal

ex: 13, 13, 14, 12

What genetic abnormality causes Down Syndrome?

Trisomy 21 (47 chromosomes, +21).

What is the frequency of Down Syndrome?

About 1 in 1500 births.

What is the Down Syndrome Critical Region (DSCR)?

A portion of chromosome 21 containing key genes (e.g., DYRK1A) responsible for most Down Syndrome symptoms.

What gene in DSCR is linked to Down Syndrome?

DYRK1A.

Which parent usually contributes the extra chromosome in Down Syndrome?

The mother is likely to carry the extra chromosome 21 because females commence meiosis early (when still in womb)

What is Turner Syndrome?

Monosomy of the X chromosome (XO female).

What gene is haploinsufficient in Turner Syndrome?

SHOX gene. In Turner Syndrome, only one SHOX gene is present, which is insufficient for normal development. This causes the growth abnormalities.

What are common symptoms of Turner Syndrome?

Short stature, infertility, and developmental abnormalities.

What genetic abnormality causes Cri-du-chat Syndrome?

Deletion of the tip of the short arm of chromosome 5 (5p–).

What are the symptoms of Cri-du-chat Syndrome?

Severe mental and physical impairment and a characteristic cat-like cry.

Which genes are implicated in Cri-du-chat Syndrome?

SEMA5A, CTNND2, and hTERT on chromosome 5p.

What is a chromosomal deletion?

Loss of a chromosome segment.

What is a chromosomal duplication?

An extra copy of a chromosome segment.

What is a chromosomal inversion?

A segment breaks, flips 180°, and reattaches.

What causes inversions?

X-rays, meiotic breakage, or transposable elements.

What is a pericentric inversion?

An inversion that includes the centromere.

What is a paracentric inversion?

An inversion that does not include the centromere.

What problem occurs when an inversion heterozygote undergoes meiosis?

The chromosomes form loops during synapsis, leading to possible unbalanced gametes.

What is a reciprocal translocation?

Exchange of segments between two nonhomologous chromosomes, usually balanced.

What is a Robertsonian translocation?

Fusion of two acrocentric chromosomes at their centromeres with loss of small tips.

What evolutionary event explains the difference in chromosome number between humans (46) and apes (48)?

A Robertsonian translocation fused two ancestral ape chromosomes into human chromosome 2.

Chromosomal Inversion

a chromosomal defect where a segment of a chromosome breaks off, flips 180 degrees, and then reattaches to the same chromosome in the reversed orientation