Chromosome and anomalies for 5 marks KUHS
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I now have all the information needed. Let me compile a comprehensive 5-mark KUHS answer on chromosomes and their anomalies.
Chromosomes and Anomalies (5 Marks - KUHS)
Structure of Normal Chromosomes (Karyotype)
Human somatic cells contain 46 chromosomes - 22 homologous pairs of autosomes and two sex chromosomes (46,XX in females; 46,XY in males).
Chromosome components:
- Centromere - constriction point; divides the chromosome into two arms
- Short arm = p (from French petit)
- Long arm = q (next letter of alphabet)
- Regions are numbered from the centromere outward (e.g., Xp21.2 = X chromosome, short arm, region 2, band 1, sub-band 2)
Karyotyping: Cells arrested in metaphase, stained with Giemsa (G-banding) - produces 400-800 bands per haploid set. This allows identification of each chromosome and detection of structural alterations.
Classification of Chromosomal Anomalies
Chromosomal disorders arise from:
- Abnormal number (numerical)
- Altered structure (structural)
I. Numerical Anomalies
Euploid: Any exact multiple of the haploid number (23).
Aneuploid: Chromosome complement NOT an exact multiple of 23.
Causes of aneuploidy:
| Mechanism | Result |
|---|---|
| Nondisjunction (failure of chromatids to separate at meiosis/mitosis) | Gamete with n+1 or n-1 chromosomes |
| Anaphase lag (chromosome fails to move, left outside nucleus) | One normal cell + one monosomic cell |
Types:
- Trisomy (2n + 1): Extra chromosome - e.g., Down syndrome (47,XY,+21)
- Monosomy (2n - 1): Missing chromosome - e.g., Turner syndrome (45,X)
- Mosaicism: Two or more populations of cells in one individual due to mitotic nondisjunction early in embryogenesis (e.g., 46,XX / 47,XX,+21)
II. Structural Anomalies
Structural changes result from chromosome breakage followed by loss or rearrangement.
1. Translocation
A segment of one chromosome is transferred to another.
- Balanced reciprocal: Single breaks in two chromosomes with exchange of material. No genetic loss - carrier is usually phenotypically normal but at risk of producing aneuploid gametes.
- Robertsonian translocation (centric fusion): Two acrocentric chromosomes (13, 14, 15, 21, 22) fuse near their centromeres. One large chromosome (two q arms) is formed; the tiny product is lost. The carrier is normal (balanced) but at risk of Down syndrome offspring. Found in 1 in 1000 individuals.
2. Isochromosome
One arm is lost and the remaining arm is duplicated - chromosome has two identical arms. Most common example: i(X)(q10) - seen in Turner syndrome variants. Results in monosomy for short arm of X and trisomy for long arm.
3. Inversion
Two breaks within a single chromosome, with reinsertion of the inverted segment.
- Paracentric: Both breaks on the same arm
- Pericentric: Breaks on opposite sides of the centromere Usually compatible with normal development unless breakpoints disrupt critical genes.
4. Deletion
Loss of a segment of a chromosome. Two types:
- Interstitial deletion: Segment between two breaks lost
- Terminal deletion: Single break, fragment with no centromere is lost Example: 46,XY,del(16)(p11.2p13.1)
5. Ring Chromosome
Break at both ends of a chromosome + fusion of the damaged ends. If significant genetic material is lost, phenotypic abnormalities result (e.g., 46,XY,r(14)). Do not behave normally in meiosis or mitosis.
III. Common Clinically Important Chromosomal Disorders
| Disorder | Karyotype | Key Features |
|---|---|---|
| Down syndrome (Trisomy 21) | 47,XX/XY,+21 (95%); Translocation type; Mosaic type | Incidence 1:700; Intellectual disability; Flat facies, epicanthic folds, oblique palpebral fissures; 40% congenital heart disease (AV septal defects most common); ↑ risk ALL and AML leukemia; Alzheimer changes by age 40; maternal age effect |
| Edwards syndrome (Trisomy 18) | 47,XX,+18 | 1:8000; Rocker-bottom feet, clenched fist, micrognathia; severe malformations; rarely survive >1 year |
| Patau syndrome (Trisomy 13) | 47,XX,+13 | 1:15,000; Holoprosencephaly, cleft lip/palate, polydactyly; severe; rarely survive >1 year |
| Turner syndrome | 45,X | Short stature, gonadal dysgenesis, webbed neck, coarctation of aorta; only viable autosomal monosomy |
| Klinefelter syndrome | 47,XXY | Tall, hypogonadism, gynecomastia, infertility |
| 22q11.2 Deletion | del(22q11.2) | DiGeorge/velocardiofacial syndrome; T-cell immunodeficiency, hypocalcemia, cardiac defects, schizophrenia risk (~25%) |
Key Points for 5 Marks
- Normal karyotype: 46 chromosomes; short arm = p, long arm = q
- Aneuploidy caused by nondisjunction (most common) or anaphase lag
- Trisomies are compatible with life; autosomal monosomies are generally lethal
- Structural anomalies include translocation, deletion, inversion, isochromosome, ring chromosome
- Down syndrome is the most common chromosomal disorder; maternal age is the strongest risk factor
- ~7.5% of all conceptions have a chromosomal abnormality; ~0.5%-1% of live births are affected
Source: Robbins, Cotran & Kumar - Pathologic Basis of Disease; Thompson & Thompson Genetics and Genomics in Medicine, 9th ed.
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