Chromosomes are compact structures of DNA and proteins that carry genes in a linear order. Most species maintain a characteristic chromosome number and structure, but molecular errors and environmental factors can produce changes in chromosome structure or number. These changes are crucial in genetics because they can lead to developmental disorders, influence fertility, create genetic diversity for evolution, and provide tools for plant and animal breeding.
- Structural variations — changes in arrangement of chromosomal segments (no change in total chromosome set number).
- Numerical variations — gain or loss of whole chromosomes or entire chromosome sets (changes in chromosome count).
Structural changes typically result from chromosome breakage followed by incorrect rejoining, or from faulty recombination events. These are often visible at the microscopic (cytogenetic) level and can be detected by karyotyping, FISH (fluorescence in situ hybridization), or molecular methods (array CGH, genome sequencing).
Definition: Loss of a chromosome segment leading to missing genes.
Mechanism: Chromosomal breakage with loss of terminal or interstitial fragments. If break occurs near the end (terminal deletion), only the terminal piece is lost; interstitial deletions remove an internal segment.
- Cri‑du‑chat syndrome (Human) — terminal deletion of the short arm of chromosome 5 (5p−). Clinical features: high‑pitched cry (like a cat), intellectual disability, microcephaly, and distinct facial features.
- Drosophila — Notched wing and visible phenotypic effects arise from X‑chromosome deletions used in classical genetics experiments.
Definition: A stretch of the chromosome is copied, producing additional genetic material.
Consequences: Increased gene dosage — can be beneficial, neutral, or deleterious depending on genes involved.
- Bar eye in Drosophila — caused by tandem duplication on the X chromosome; heterozygotes have narrowed eyes and homozygotes show stronger phenotype.
- Charcot‑Marie‑Tooth disease type 1A (Human) — duplication of the PMP22 gene on chromosome 17 leads to peripheral neuropathy.
Definition: A chromosome segment breaks and reinserts in the reverse orientation. Gene content remains the same but order is reversed.
Types:
- Paracentric — inversion does not include the centromere.
- Pericentric — inversion includes the centromere.
Cytogenetic effect: During meiosis of inversion heterozygotes an inversion loop forms. Crossing over within the loop can produce acentric/dicentric chromosomes (paracentric) or duplications/deletions (pericentric), often causing gamete inviability.
- Drosophila melanogaster — many natural populations show paracentric inversions associated with adaptation to local climates.
- Human chromosome 9 inversion — pericentric inversion of chromosome 9 (inv(9)(p11q13)) is common and often considered a normal variant but has been associated with infertility and recurrent abortions in some studies.
Definition: Transfer of chromosomal segments between non‑homologous chromosomes. Can be balanced (no net gain/loss of genetic material) or unbalanced.
Types:
- Reciprocal translocation: Mutual exchange of segments between two chromosomes.
- Robertsonian translocation: Fusion of two acrocentric chromosomes at or near their centromeres forming a single chromosome (commonly seen in human chromosomes 13, 14, 15, 21, 22).
- Philadelphia chromosome (Human) — t(9;22)(q34;q11) creates BCR‑ABL fusion gene producing a constitutively active tyrosine kinase; hallmark of chronic myeloid leukemia (CML).
- Robertsonian translocation involving chromosome 21 — a common parental balanced translocation that can give rise to offspring with Robertsonian translocation Down syndrome (phenotypically similar to free trisomy 21).
- Plant breeding: Translocations have been manipulated to transfer disease resistance genes from wild relatives into crops (e.g., wheat).
Definition: A chromosome with two identical arms (either two p arms or two q arms), formed by misdivision through the centromere or by mirror‑image duplication.
- Turner Syndrome variants: Some Turner patients (45,X) can have an isochromosome of the long arm of X (i(Xq)), causing loss of short arm genes and clinical features of Turner syndrome.
- Gene dosage imbalance: Deletions and duplications change copy number of genes — many developmental disorders are dosage sensitive.
- Position effect: When a gene is moved near heterochromatin or new regulatory elements (e.g., by inversion or translocation), its expression may be altered without changing sequence.
- Reproductive failure: Balanced carriers of inversions/translocations may be phenotypically normal but produce unbalanced gametes leading to miscarriages, infertility, or affected offspring.
- Cancer: Many cancers arise from structural rearrangements that create fusion oncogenes (e.g., BCR‑ABL, PML‑RARα).
Numerical changes alter chromosome numbers and arise from nondisjunction (failure of chromosomes to segregate evenly) during meiosis or mitosis. Molecular causes include spindle defects, cohesion failures, or environmental insults.
Definition: Cells with chromosome numbers that are not exact multiples of the haploid set (e.g., 2n + 1, 2n − 1).
Causes: Nondisjunction during meiosis I or II, or mitotic errors after fertilization (leading to mosaicism).
- Down's syndrome (Trisomy 21) — presence of an extra chromosome 21. Clinical features: intellectual disability, characteristic facial features, hypotonia, and congenital heart defects. Most commonly due to maternal meiotic nondisjunction and incidence increases with maternal age.
- Edwards syndrome (Trisomy 18) — severe developmental defects; low survival.
- Patau syndrome (Trisomy 13) — severe malformations including cleft lip/palate, polydactyly.
- Turner syndrome (45,X) — monosomy X in females: short stature, gonadal dysgenesis, webbed neck.
- Klinefelter syndrome (47,XXY) — males with an extra X: tall stature, hypogonadism, infertility, variable learning difficulties.
- Often deleterious in animals because of complex dosage imbalances across many genes.
- Many aneuploid embryos are non‑viable and result in early miscarriage.
- In cancer, aneuploid karyotypes are common and may contribute to tumor progression.
Definition: Addition or loss of one or more complete haploid sets of chromosomes (e.g., 3n, 4n).
Example: Male honey bees (Apis) are haploid (n) and develop from unfertilized eggs — a natural example of monoploidy.
Definition: Presence of more than two complete sets of chromosomes in a cell (common in plants).
Types:
- Autopolyploidy — multiplication of the same genome (e.g., 2n → 4n). Often produced by chromosome doubling (colchicine treatment) or by unreduced gametes.
- Allopolyploidy — combination of two or more distinct genomes by hybridization followed by chromosome doubling (e.g., hybrid of species A and B → genome AB; doubling gives AABB).
- Bread wheat (Triticum aestivum) — hexaploid (2n = 6x = 42) formed by successive allopolyploid events combining genomes from three species. Polyploidy contributed to larger seeds and adaptability.
- Banana — many cultivated bananas are triploid (3n) and sterile; this is exploited to produce seedless fruits.
- Cotton — allotetraploid species (Gossypium hirsutum) used in textile industry.
- Heterosis and vigor: Polyploids often show increased cell size (gigantism), larger organs, and sometimes greater stress tolerance.
- Reproductive isolation: Polyploidy can create instant speciation because polyploid individuals are reproductively isolated from their diploid parents.
- Agricultural uses: Breeders induce polyploidy (using colchicine) to develop seedless fruits, larger tubers, or improved crop varieties.
Different techniques are used depending on resolution required:
- Karyotyping — classical cytogenetics visualizing metaphase chromosomes (good for large structural changes and aneuploidy).
- FISH (Fluorescence In Situ Hybridization) — uses fluorescent probes to detect presence/position of specific DNA sequences (good for translocations, microdeletions).
- Array Comparative Genomic Hybridization (array‑CGH) — detects copy number variations (duplications/deletions) genome‑wide at high resolution.
- Next‑generation sequencing — whole genome or targeted sequencing reveals breakpoints, small deletions/insertions, and complex rearrangements.
- Medical genetics: Diagnosis of congenital syndromes (e.g., prenatal screening for trisomy 21 by karyotype or non‑invasive prenatal testing), cancer cytogenetics for targeted therapy (e.g., tyrosine kinase inhibitors for BCR‑ABL).
- Evolutionary biology: Structural rearrangements and polyploidy contribute to genetic divergence and speciation. Chromosome changes shape gene flow and reproductive compatibility.
- Plant and animal breeding: Artificially induced polyploidy or introgression via translocations expand trait variation. Triploid seedless fruits and polyploid ornamentals are practical outcomes.
- Research tools: Deletion mapping, duplication lines, and translocation stocks are classical genetic resources in model organisms (e.g., Drosophila, maize) used to locate genes and study gene function.
- Structural variations change gene order and content on chromosomes; numerical variations change chromosome counts.
- Many structural changes are balanced carriers (phenotypically normal) but cause reproductive problems; unbalanced changes often produce abnormal phenotypes or lethality.
- Aneuploidy is commonly harmful in animals, while polyploidy often benefits plants and has major agricultural importance.
- Cytogenetic techniques range from karyotyping to sequencing — choose based on the size and type of variation to detect.
| Aspect | Structural Variation | Numerical Variation |
|---|---|---|
| What changes? | Arrangement or copy number of segments within chromosomes | Number of entire chromosomes or whole chromosome sets |
| Main causes | Breakage and misrepair, unequal crossing‑over | Non‑disjunction, spindle defects, unreduced gametes |
| Visible by karyotype? | Often yes (large changes) | Yes (aneuploidy and polyploidy) |
| Common in plants? | Yes — contributes to speciation | Polyploidy very common |
| Impact in humans | Can cause disease (e.g., translocations → cancer) | Aneuploidies cause syndromes (Down, Turner) |
- Practice drawing karyotypes and inversion loops — visual learning helps remember meiotic consequences.
- Learn major human syndromes (Down, Turner, Klinefelter) with karyotype notation and key clinical features.
- Explore plant examples (wheat, banana, cotton) to understand applied polyploidy in agriculture.
- Read short research articles on cancer cytogenetics (BCR‑ABL, PML‑RARα) to see clinical applications.
