Definition of Chromosomes

Chromosomes are thread-like structures found in the nucleus of a cell, visible during cell division.
They are made up of DNA and proteins, where DNA contains genes—units of inheritance responsible
for traits—and proteins help in maintaining their structure and function.

Examples of Organisms and Chromosome Numbers

1. Penicillium: 1 pair of chromosomes

2. Mosquito: 6 chromosomes
3. Honeybee: 32 chromosomes
4. Corn: 20 chromosomes
5. Sugarcane: 80 chromosomes
6. Mouse: 40 chromosomes
7. Human: 46 chromosomes (23 pairs)

Key Points

• Chromosomes carry genetic material essential for an organism’s survival.

• A lack or loss of chromosomes leads to severe consequences, including
developmental issues or death.

Types of Chromosomes
a. Autosomes and Sex Chromosomes

1. Autosomes:

• Chromosomes that do not determine the sex of an individual.

• Carry genes for various traits unrelated to sex.
• Humans have 22 pairs of autosomes.

2. Sex Chromosomes:

• Chromosomes that determine the sex of an individual.

• Humans have 1 pair of sex chromosomes:
• XX in females.
• XY in males.

b. Homologous and Non-Homologous Chromosomes

1. Homologous Chromosomes:
• A pair of chromosomes, one from each parent, with the same length, gene position,
and centromere location.
• Carry genes for the same traits but may have different alleles.
• Example: Chromosome 1 from the father and Chromosome 1 from the mother.

2. Non-Homologous Chromosomes:

• Chromosomes that do not belong to the same pair.

• Differ in size, shape, and gene content.
 • Example: Chromosome 1 and Chromosome 2 in humans.

c. Types of Chromosomes Based on Centromere Position

1. Telocentric Chromosome:

• Centromere at the tip, with no short arm.

• Shape: Straight “I”.

2. Acrocentric Chromosome:

• Centromere near the end, with one very short arm and one long arm.
• Shape: “J”.

3. Sub-Metacentric Chromosome:

• Centromere slightly away from the center, creating one arm slightly longer than the
other.
• Shape: “L”.

4. Metacentric Chromosome:

• Centromere located in the center, dividing the chromosome into two equal arms.
• Shape: “V”.

Structure of Chromosomes
1. Chromatids:

• Two identical strands of a chromosome, each with a single DNA molecule.

2. Centromere (Primary Constriction):

• Region where sister chromatids are joined.

• Divides the chromosome into two arms.

3. Secondary Constriction (Nucleolar Organizer Region):

• Forms the nucleolus during interphase.

4. Satellite:

• A knob-like structure at the end of some chromosomes.

• Contains junk DNA (non-coding DNA).

5. Telomeres:

• Terminal ends of chromosomes.

• Prevent chromosomes from sticking to each other and protect genetic material
during replication.

• Karyotype
 • The specific arrangement of chromosomes in an individual.
• Varies among species and individuals.
• Helps identify chromosomal abnormalities and differences.
•

20.1.3 Levels of Eukaryotic Chromosomal Organization

1. DNA Double Helix (2 nm)

• The fundamental structure of DNA, consisting of two complementary strands coiled

around each other.
• Length of DNA in one human cell: ~2 meters; compacted to fit inside the nucleus
(~10 µm).

2. Nucleosome String (10 nm)

• DNA wraps around a core of 8 histone proteins at regular intervals, forming bead-like
structures called nucleosomes.
• Linker DNA connects nucleosomes, giving the “beads-on-a-string” appearance.
• Shortens the DNA by 7-fold.

3. Chromatin Fiber (30 nm)

• The nucleosome string coils into a thicker fiber (~30 nm).

• Contains two types:
• Heterochromatin: Highly condensed; transcriptionally inactive.
• Euchromatin: Less condensed; transcriptionally active.

4. Supercoil (300 nm)

• Chromatin fibers coil further, forming loops supported by a scaffold of fibrous

proteins.
• This level is seen during early stages of chromosome condensation.

5. Chromatid (700 nm)

• Formed by additional coiling of supercoils.

• Visible during cell division as sister chromatids attached at the centromere.

6. Metaphase Chromosome (1400 nm)

• Fully condensed chromosome, visible under a microscope during metaphase.

• Essential for equal distribution of genetic material during mitosis and meiosis.

These hierarchical levels of compaction allow DNA to fit inside the nucleus while maintaining
accessibility for replication and transcription.
20.1.4 Chromosome Karyotype
1. Definition

• Karyotype: The complete set of chromosomes in a cell, arranged based on size,

shape, and number.
• Karyogram: A visual representation of a karyotype, showing the arrangement of
chromosomes (e.g., human karyotype has 46 chromosomes).

2. Features of a Karyotype

• Chromosomes differ in size, centromere position, and banding patterns (stained for
identification).
• Number of chromosomes varies among species:
• Humans: 46 chromosomes (23 pairs).
• Haploid human nucleus (sperm/egg): 23 chromosomes (n=23).
• Diploid human nucleus: 46 chromosomes (2n=46).

3. Autosomes and Sex Chromosomes

• Autosomes: Chromosomes that are the same in both sexes (22 pairs in humans).
• Sex Chromosomes: Determine the sex of an individual.
• Males: XY.
• Females: XX.
• In humans, the Y chromosome carries the TDF gene, which triggers the development
of testes.

4. Aneuploidy (Abnormal Chromosome Numbers)

• Aneuploidy: Gain or loss of a chromosome.

• Monosomy (2n-1): Loss of one chromosome (e.g., Turner Syndrome: 45, X).
• Trisomy (2n+1): Addition of one chromosome (e.g., Trisomy 21 causes Down
syndrome).
• Caused by non-disjunction: Failure of chromosomes to separate during meiosis or
mitosis.

5. Structural Chromosome Abnormalities

• Deletion: Loss of a chromosome segment.

• Duplication: Extra copy of a chromosome segment.
• Inversion: A chromosome segment is reversed.
• Insertion: DNA from one chromosome is added to a non-homologous chromosome.
• Translocation: Reciprocal exchange of segments between two non-homologous
chromosomes.
• These defects may cause genetic disorders or contribute to evolution (e.g., gene
duplication leading to novel traits).

6. Applications of Karyotyping

• Detecting genetic disorders (e.g., Down syndrome, Turner syndrome).

• Studying evolutionary relationships.
• Identifying chromosomal abnormalities.
Karyotypes are a fundamental tool in genetics to study chromosome number, structure, and
abnormalities.

20.1.5 Differentiating Between Heterochromatin and Euchromatin

1. Definition and Location

• Heterochromatin:
• Tightly packed, condensed chromatin.
• Found at the centromeres, telomeres, and other specific regions of chromosomes.
• Euchromatin:
• Loosely packed, less condensed chromatin.
• Found in the active regions of chromosomes.

2. Gene Expression

• Heterochromatin:
• Inactive or unexpressed DNA regions (genes are not transcribed).
• Euchromatin:
• Active DNA regions (genes are transcribed and expressed).

3. Appearance

• Heterochromatin: Darkly stained under a microscope.

• Euchromatin: Lightly stained under a microscope.

4. Role During Cell Division

• Heterochromatin: Always remains condensed, even when the cell is not dividing.
• Euchromatin: Condenses only during cell division to form compact chromosomes.

5. Significance

• Heterochromatin maintains structural integrity and protects inactive DNA.

• Euchromatin allows access for transcription, enabling gene expression and cellular
functions.

Summary Table

Feature Heterochromatin Euchromatin

Packing Tightly packed Loosely packed
Gene Activity Inactive (unexpressed) Active
Staining Darly Stained Lightly Stained
Role Structural Support Gene Transcription
Condensation Always Condensed Condenses only during division
Here’s a more concise version while retaining all key details:

Chromosomal Theory of Inheritance: Key Points

1. Early Contributions:

• Karl Correns (1900): Suggested genes are on chromosomes, but lacked experimental
evidence.
• Walter Sutton & Theodor Boveri (1902): Proposed that chromosomes carry genes
and follow Mendel’s laws during meiosis.

2. Supporting Evidence:

• Reproduction: Sperm and egg contribute equally to heredity, with hereditary

material in the nucleus (where chromosomes are found).
• Meiosis: Diploid cells have homologous chromosomes, while gametes have one copy,
consistent with Mendel’s laws of segregation and independent assortment.

3. Challenges:

• Discrepancy: Organisms often have more independently assorting traits than

chromosome pairs, challenging Sutton’s theory.

4. Thomas Hunt Morgan (1910):

• Experiment: Studied Drosophila melanogaster and discovered a white-eye mutant

male.
• F1 cross: All red-eyed flies, showing that the white-eye allele is recessive.
• F2 cross: 18% white-eyed flies, but all white-eyed flies were male.
• Sex-Linked Inheritance: The white-eye gene is on the X chromosome. Male flies
inherit their X chromosome from their mother, explaining the sex-specific
inheritance pattern.

5. Conclusion:

• Morgan’s Contribution: Demonstrated that genes are on chromosomes, and sex-

linked traits follow the inheritance of sex chromosomes.
• Chromosomal Theory: Validated by Morgan’s findings that chromosomes, especially
sex chromosomes, are the carriers of genes.

Key Contributions:
• Correns (1900): Suggested genes are on chromosomes.
• Sutton & Boveri (1902): Proposed chromosomes carry genes.
• Morgan (1910): Confirmed genes are on chromosomes, with sex-linked inheritance
in fruit flies.
Final Implication:
The chromosomal theory, supported by Morgan’s work, confirmed that chromosomes, particularly
sex chromosomes, are the physical carriers of genetic material.

20.3.1 explain deoxyribonucleic acid (DNA) as a heredity material with reference to the experiments
conducted by Frederick Griffith, Colin Macleod and Maclyn McCarty and Alfred Hershey and Martha
Chase;

1. Griffith’s Experiment (1928)

• Objective: Understand the genetic basis of bacterial virulence in Streptococcus

pneumoniae.
• Bacterial Strains:
• S-type (Smooth): Virulent, has a polysaccharide capsule that protects it from the
immune system.
• R-type (Rough): Non-virulent, lacks a polysaccharide capsule.
• Procedure & Observations:
• Injected S-type bacteria → Mice died.
• Injected R-type bacteria → Mice survived.
• Injected heat-killed S-type → Mice survived.
• Injected a mixture of heat-killed S-type and live R-type → Mice died.
• Result: Blood of dead mice contained live S-type bacteria.
• Conclusion:
• A “transforming principle” transferred genetic information from the dead S-type to
the live R-type, transforming them into virulent S-type.

2. Avery, MacLeod, and McCarty’s Experiment (1944)

• Objective: Identify the “transforming principle” responsible for genetic transfer.

• Method:
• Prepared a mixture of heat-killed S-type and live R-type bacteria, similar to Griffith’s
experiment.
• Removed proteins, carbohydrates, and lipids from the solution to isolate nucleic
acids.
• Treated the solution with enzymes:
• Protease: No effect, transformation occurred.
• RNase: No effect, transformation occurred.
• DNase: Destroyed the transforming ability.
• Conclusion: DNA is the “transforming principle” responsible for transferring genetic
information.

3. Hershey and Chase Experiment (1952)

• Objective: Confirm whether DNA or protein is the hereditary material in

bacteriophages.
 • Background:
• Bacteriophages (viruses) infect bacteria and reproduce by injecting their genetic
material into host cells.
• Phages are composed of DNA and protein.
• Method:
• Labeled phages with radioactive isotopes:
• 32P to label DNA (phosphorus is found in DNA, not proteins).
• 35S to label proteins (sulfur is found in proteins, not DNA).
• Allowed labeled phages to infect E. coli bacteria.
• After infection:
• Used centrifugation to separate the bacterial cells from phage protein coats.
• Measured radioactivity in the bacteria and the surrounding solution.
• Observations:
• 32P (DNA) was found inside the bacterial cells.
• 35S (protein) remained outside the bacterial cells.
• Phages produced in infected bacteria contained 32P, confirming DNA was passed on.
• Conclusion: DNA, not protein, is the hereditary material that directs the production
of new viruses.

Key Findings & Significance

1. Griffith’s Transformation: First evidence that genetic material could be transferred

between organisms.

2. Avery’s Experiment: Identified DNA as the molecule responsible for heredity.

3. Hershey-Chase Experiment: Definitively confirmed DNA as the hereditary material,

not protein.

Why DNA and Not Protein?

• Proteins were initially considered stronger candidates for heredity due to their
complexity.
• DNA was initially thought to be too simple because of its uniform structure.
• These experiments proved that DNA, though chemically simpler, carries all genetic
instructions.

Watson and Crick’s Model of DNA

Structure of DNA

1. Double Helix:

• DNA consists of two strands twisted into a right-handed helix.

• Strands are antiparallel: one runs 5’ to 3’, the other 3’ to 5’.
 2. Backbone:

• Sugar-phosphate backbone is on the outside.

• Provides structural stability and interacts with the aqueous environment.

3. Base Pairing:

• Bases face inward and pair specifically:

• Adenine (A) pairs with Thymine (T) via 2 hydrogen bonds.
• Guanine (G) pairs with Cytosine (C) via 3 hydrogen bonds.
• Pairing ensures a uniform helix diameter (2 nm).

4. Measurements:

• One full turn = 3.4 nm.

• 10 base pairs per turn.
• Bases are stacked 0.34 nm apart.

Key Rules and Insights

1. Chargaff’s Rule:

• A = T and G = C in proportion.
• Purines (A, G) pair with pyrimidines (T, C) to maintain helix uniformity.

2. Stability:

• Hydrogen bonds and base stacking interactions stabilize the structure.

• Biological Significance
• The model suggested the mechanism for DNA replication:
• Each strand acts as a template for forming a complementary strand.
• Explained how genetic information is stored in the sequence of bases.

Historical Context

1. Contributions to the Model:

• Rosalind Franklin’s X-ray diffraction data revealed DNA’s helical shape and
dimensions.
• Erwin Chargaff’s findings highlighted base-pairing rules.

2. Recognition:

• Watson, Crick, and Wilkins won the Nobel Prize in 1962.

• Franklin’s contributions were critical but unrecognized during her lifetime.

• Visual Representation
• Sugar-phosphate backbone = side ropes of a twisted ladder.
 • Base pairs = rungs of the ladder.
• Twist forms a helix.

20.4.3: Semi-Conservative Replication of DNA (Detailed Notes)

1. Semi-Conservative Model

• Proposed by Meselson & Stahl.

• Result: Each daughter DNA molecule contains 1 parental strand (template) and 1
new complementary strand.

2. Origins of Replication

• Bacteria: Single origin on circular DNA.

• Eukaryotes: Multiple origins on linear DNA (100s–1,000s origins).
• Replication begins at origins, forming replication bubbles that expand and fuse to
speed up the process.

3. Replication Fork Components

• Helicase: Unwinds the double helix at replication forks.

• Single-Strand Binding Proteins (SSBs): Bind to separated strands to prevent re-
annealing.
• Topoisomerase: Relieves strain caused by unwinding by cutting, swiveling, and
rejoining DNA strands.

4. Primer Formation

• Primase: Synthesizes a short RNA primer (~5–10 nucleotides).

• RNA primer provides a free 3’-OH for DNA polymerase to add nucleotides.

5. DNA Synthesis

• DNA Polymerase III (Prokaryotes): Adds nucleotides in the 5’ → 3’ direction

complementary to the parental strand.
• Leading Strand: Synthesized continuously towards the replication fork.
• Lagging Strand: Synthesized discontinuously as Okazaki fragments (100–200
nucleotides in eukaryotes; 1,000–2,000 in prokaryotes).

6. Processing of Okazaki Fragments

• DNA Polymerase I (Prokaryotes): Replaces RNA primers with DNA.

• DNA Ligase: Seals gaps between fragments by joining sugar-phosphate backbones.

7. Nucleotides & Energy

• Nucleotides: dATP, dTTP, dGTP, dCTP.

• Energy source: Hydrolysis of pyrophosphate (PPi) into 2 inorganic phosphates (Pi).

8. Speed of Replication

• Prokaryotes: ~500 nucleotides/sec.

 • Eukaryotes: ~50 nucleotides/sec (slower due to chromatin and multiple replication
forks).

9. Replication Complex (DNA Replication Machine)

• Proteins involved form a replication complex.

• Trombone Model: Lagging strand loops through the complex for
simultaneous synthesis of both strands.
• Complex may remain stationary, with DNA moving through it.

10. Proofreading & Fidelity

• DNA Polymerases proofread via 3’ → 5’ exonuclease activity to remove

mismatched bases, ensuring high accuracy.

• Key Figures and Mechanisms

• Replication Bubble: Opens bidirectionally from the origin, forming replication forks.
• Okazaki Fragments: Unique to the lagging strand; joined by DNA ligase.
• Directionality: DNA strands are antiparallel (5’ → 3’ vs. 3’ → 5’), restricting
polymerase function.

20.5.1: Describe Gene and Genetic Code

Gene
• A gene is a specific sequence of nucleotides along the DNA strand.
• Function:
• It contains instructions to synthesize a protein or enzyme that determines specific
traits or controls a particular function.
• Proteins are the link between genotype (genetic makeup) and phenotype (physical
traits).
• Expression:
• A gene expresses itself through protein synthesis, which involves two processes:
• Transcription: Synthesis of RNA from DNA.
• Translation: Decoding of RNA to form proteins.

• Genetic Code
• The genetic code is the sequence of nucleotides in DNA that is transcribed into
mRNA for protein synthesis.
• Codon:
• A triplet of mRNA bases (e.g., AUG) that codes for one amino acid.
• There are 64 codons:
• 61 sense codons encode amino acids.
• 3 stop codons (UAA, UAG, UGA) signal the end of translation.
• Start codon: AUG (methionine).
Characteristics of the Genetic Code
1. Triplet Nature:

• Each codon consists of three nucleotides, sufficient to encode 20 amino acids.

2. Degeneracy:

• Most amino acids are encoded by multiple codons. E.g., Leucine and Serine have 6
codons each.

3. Universality:

• The genetic code is conserved across most organisms. E.g., AGA codes for arginine in
humans and bacteria.
• Exception: Mitochondria show variations.

4. Non-Overlapping:

• Codons are read sequentially without overlapping.

• E.g., AUGAGCGCA is read as AUG / AGC / GCA.

5. No Punctuation:

• Codons are read continuously without gaps between them.

20.5.2: Describe One Gene-One Enzyme Hypothesis

One Gene-One Enzyme Hypothesis

• Proposed by George Beadle and Edward Tatum in 1941.
• States that each gene in an organism’s genome controls the production of a single
specific enzyme.

Key Experiment
• Organism Used: Neurospora crassa (bread mold).
• Method:
• Exposed mold spores to X-rays to induce mutations.
• Grew mutants on minimal medium (lacking certain nutrients).
• Some mutants failed to grow unless specific nutrients (e.g., amino acids) were
added.

Conclusion:
• Mutations in specific genes disrupted the synthesis of enzymes needed for metabolic
pathways.
• Each defective gene corresponded to a defective enzyme.
Modified Understanding
1. One Gene-One Polypeptide Hypothesis:

• Later research revealed that some proteins consist of multiple polypeptides.

• Each polypeptide is encoded by a specific gene.

2. One Gene-Multiple Products:

• Alternative splicing allows a single gene to produce multiple polypeptides.

3. Not All Genes Code for Proteins:

• Some genes code for functional RNAs (e.g., tRNA, rRNA).

Significance
• Laid the foundation for understanding gene function in protein synthesis.
• Highlighted the relationship between genes, proteins, and metabolic pathways.

20.5.3: Explain the Mechanism of Protein Synthesis by Means of DNA and

RNA

Protein synthesis involves two key processes: Transcription (DNA to RNA) and Translation (RNA to
Protein). Together, they convert genetic information into functional proteins.

1. Transcription (DNA → RNA)

• Definition: RNA synthesis using DNA as a template.

• Occurs In: Nucleus (eukaryotes) or cytoplasm (prokaryotes).
• Key Enzyme: RNA Polymerase.
• Phases:
• Initiation:
• RNA polymerase binds to the promoter region (e.g., TATA box).
• DNA unwinds, exposing the template strand (antisense strand).
• Elongation:
• RNA polymerase adds complementary ribonucleotides (A-U, T-A, G-C, C-G) to
synthesize pre-mRNA (5′ → 3′ direction).
• DNA re-winds as RNA polymerase moves forward.
• Termination:
• RNA polymerase detaches when it reaches the terminator region, releasing pre-
mRNA.

Post-Transcriptional Modifications (Eukaryotes):

1. Capping: Addition of a 5′ cap (7-methylguanosine) to protect RNA.

 2. Polyadenylation: Addition of a poly-A tail at the 3′ end for stability.
3. Splicing: Removal of introns (non-coding sequences) and joining of exons (coding
sequences) by spliceosomes, forming mature mRNA.

2. Translation (RNA → Protein)

• Definition: Protein synthesis from mRNA using ribosomes.

• Occurs In: Cytoplasm (on ribosomes).
• Key Components: mRNA, tRNA, ribosomes, amino acids, enzymes.

Phases:

1. Activation of Amino Acids:

• Amino acids bind to specific tRNA molecules (3′ end) using aminoacyl-tRNA
synthetase.

2. Initiation:

• Small ribosomal subunit binds to mRNA at the start codon (AUG).

• Initiator tRNA (methionine) pairs with AUG at the P-site.
• Large ribosomal subunit attaches, forming the initiation complex.

3. Elongation:

• A-site: New tRNA carrying amino acid pairs with codon.

• P-site: Peptide bond forms between amino acids, catalyzed by peptidyl transferase.
• Ribosome translocates:
• Empty tRNA exits from the E-site.
• Growing polypeptide shifts to the P-site.

4. Termination:

• Ribosome reaches stop codon (UAA, UAG, UGA).

• Release factors bind, releasing the polypeptide chain.
• Ribosome detaches from mRNA.

3. The Genetic Code

• Definition: Nucleotide triplets (codons) in mRNA that specify amino acids.

• Features:

1. Triplet Code: 3 bases = 1 codon = 1 amino acid.

2. Start Codon: AUG (Methionine).
3. Stop Codons: UAA, UAG, UGA (do not code for amino acids).
4. Degeneracy: Some amino acids are coded by multiple codons.
5. Universal and Non-Overlapping: Genetic code is the same across most organisms and
codons are read sequentially without gaps.
4. Significance of Protein Synthesis

• Essential for gene expression and cellular functions.

• Links genotype (genetic code) to phenotype (observable traits).
• Produces proteins that serve structural, catalytic, and regulatory roles.

20.6.1 Types of Mutation

A mutation is a permanent change in the DNA sequence that can affect the structure or function of
proteins. Mutations can occur spontaneously (due to errors in DNA replication) or be induced by
environmental factors (mutagens).

Mutations are categorized based on where they occur and their effect on DNA structure:

1. Chromosomal Mutations (Chromosomal Aberrations)

These mutations involve large-scale changes in chromosomes, affecting multiple genes. They occur
due to errors in meiosis (during gamete formation) or external factors like radiation.

A. Numerical Chromosomal Mutations (Aneuploidy & Polyploidy)

• Aneuploidy: Changes in the number of chromosomes due to improper segregation in

meiosis.
• Monosomy (2n - 1): One missing chromosome (e.g., Turner syndrome - 45, XO).
• Trisomy (2n + 1): One extra chromosome (e.g., Down syndrome - Trisomy 21).
• Polyploidy: Having extra sets of chromosomes (e.g., 3n or 4n) – rare in animals,
common in plants.

B. Structural Chromosomal Mutations

• Deletion: A part of the chromosome is lost (e.g., Cri-du-chat syndrome – deletion on

chromosome 5).
• Duplication: A segment of the chromosome is repeated, leading to excessive gene
expression.
• Inversion: A chromosome segment flips and reattaches in reverse order, disrupting
gene function.
• Translocation: A fragment from one chromosome attaches to another, often causing
diseases like chronic myeloid leukemia (CML).

2. Gene Mutations (Point Mutations)

These affect one or a few nucleotides in a single gene, altering the protein’s structure or function.

A. Types of Point Mutations

1. Substitution Mutations (Single Base Change):

• Silent Mutation: No change in amino acid (due to redundancy in the genetic code).
• Missense Mutation: Changes one amino acid (e.g., sickle cell anemia – glutamic acid
→ valine).
• Nonsense Mutation: Converts a codon into a STOP codon, creating an incomplete
protein (e.g., Duchenne muscular dystrophy).

2. Insertion & Deletion Mutations:

• Frameshift Mutation: Addition or removal of a nucleotide shifts the reading frame,

leading to a completely different protein (e.g., Tay-Sachs disease).
• In-frame Insertion/Deletion: Addition or deletion of nucleotides in multiples of 3,
affecting one or more amino acids but not the entire sequence.

3. Mutations Based on Cause (Spontaneous vs. Induced Mutations)

• Spontaneous Mutations: Occur naturally due to errors in DNA replication or repair

mechanisms.
• Induced Mutations: Caused by mutagens such as radiation, chemicals, and viruses.

4. Mutations Based on Effect on Function

• Beneficial Mutations: Provide an advantage (e.g., lactase persistence in humans).

• Neutral Mutations: No significant effect on the organism.
• Harmful Mutations: Cause diseases or decrease survival chances (e.g., cancer-
causing mutations in tumor suppressor genes like p53).

Key Takeaways

• Chromosomal mutations affect large DNA segments and cause syndromes like Down
syndrome and Turner syndrome.
• Gene mutations (point mutations) involve small changes in the DNA sequence and
may cause diseases like sickle cell anemia and PKU.
• Mutations can be spontaneous (natural errors in replication) or induced (caused by
mutagens like radiation and chemicals).
• Some mutations are beneficial and drive evolution, while others cause severe
genetic disorders.
20.6.2 Differentiate Between Chromosomal Aberration and Gene Mutation

Mutations are changes in the DNA sequence that can occur at different levels. Based on their impact,
they are classified into chromosomal aberrations and gene mutations.

Differences Between Chromosomal Aberration and Gene Mutation:

1. Definition:

• Chromosomal Aberration: Large-scale changes in the structure or number of

chromosomes.
• Gene Mutation: Small-scale changes affecting one or a few nucleotides within a
gene.

2. Cause:

• Chromosomal Aberration: Errors in meiosis (nondisjunction, translocation, deletion,

etc.).
• Gene Mutation: Errors in DNA replication, mutagens (radiation, chemicals, etc.).

3. Effect:

• Chromosomal Aberration: Affects multiple genes at once.

• Gene Mutation: Alters a single gene.

4. Types:

• Chromosomal Aberration:

1. Numerical Changes (Aneuploidy & Polyploidy) → e.g., Down syndrome (Trisomy 21).

2. Structural Changes → Deletion, duplication, inversion, translocation.

• Gene Mutation:

1. Point Mutation → Substitution (silent, missense, nonsense).

2. Frameshift Mutation → Insertion or deletion of nucleotides.

5. Examples:

• Chromosomal Aberration:
• Down syndrome (Trisomy 21) → Extra chromosome 21.
• Turner syndrome (XO) → Missing X chromosome.
• Klinefelter syndrome (XXY) → Extra X chromosome in males.
• Gene Mutation:
• Sickle cell anemia → Missense mutation (glutamic acid → valine).
• Phenylketonuria (PKU) → Defective enzyme due to gene mutation.
• Cystic fibrosis → Deletion of three nucleotides in CFTR gene.

6. Severity:

• Chromosomal Aberration: Usually more severe as it affects multiple genes.

 • Gene Mutation: Can be mild to severe, depending on the gene and mutation type.

Key Takeaways:

• Chromosomal aberrations are large-scale changes affecting multiple genes, often

leading to developmental disorders.
• Gene mutations are small-scale changes affecting a single gene, leading to specific
genetic diseases.
• Both types can be inherited or caused by mutagens (radiation, chemicals, viruses).

20.6.3 Chromosomal Aberration and Its Effects

1. Definition

Chromosomal aberrations are large-scale mutations involving changes in the structure or number of
chromosomes. These occur due to errors in meiosis or exposure to mutagenic agents like radiation
and chemicals. Such changes can cause severe genetic disorders and developmental abnormalities.

2. Types of Chromosomal Aberrations

There are two main types of chromosomal aberrations:

1. Numerical Aberrations (Aneuploidy & Polyploidy) – Changes in the number of

chromosomes.

2. Structural Aberrations – Changes in the structure of chromosomes.

A. Numerical Aberrations (Aneuploidy & Polyploidy)

Aneuploidy occurs due to nondisjunction, where chromosomes fail to separate properly during
meiosis. This results in an extra or missing chromosome. Common examples include:

• Down Syndrome (Trisomy 21) – Caused by an extra chromosome 21, leading to

intellectual disabilities, heart defects, and characteristic facial features.
• Turner Syndrome (XO) – Occurs in females missing one X chromosome, resulting in
short stature, infertility, and heart defects.
• Klinefelter Syndrome (XXY) – Males with an extra X chromosome, leading to
infertility, reduced testosterone levels, and learning difficulties.
Polyploidy is the presence of extra sets of chromosomes (e.g., 3n or 4n). It is lethal in humans but
beneficial in plants, where it leads to larger fruits and flowers (e.g., wheat and strawberries).

B. Structural Aberrations

1. Deletion – A part of a chromosome is lost, removing multiple genes. An example is Cri-du-

chat syndrome, where a deletion on chromosome 5 causes severe mental retardation,
abnormal facial features, and a high-pitched crying sound in infants.

2. Duplication – A segment of a chromosome is copied, leading to extra genetic material. This

can cause genetic disorders like Charcot-Marie-Tooth disease, a neuromuscular disorder
affecting movement and balance.

3. Inversion – A chromosome segment breaks, flips, and rejoins in reverse order. While often
harmless, it can cause miscarriages or infertility when chromosomes fail to pair correctly in
meiosis.

4. Translocation – A piece of a chromosome attaches to a non-homologous chromosome. An

example is the Philadelphia Chromosome, where a translocation between chromosomes 9
and 22 leads to chronic myeloid leukemia (CML).

4. Effects of Chromosomal Aberrations

Chromosomal aberrations disrupt gene function, leading to various disorders and developmental
problems, including:

• Physical and intellectual disabilities (e.g., Down syndrome, Cri-du-chat syndrome).

• Infertility (e.g., Turner syndrome, Klinefelter syndrome).
• Increased risk of cancer (e.g., Philadelphia chromosome and leukemia).
• Miscarriages and stillbirths due to improper chromosome segregation.

Since chromosomal aberrations involve large genetic changes, they cannot be reversed, but
management strategies like hormonal therapy, medications, and supportive care can improve quality
of life for affected individuals.

20.6.4 Gene Mutation and Its Causes

1. Definition
A gene mutation is a change in the nucleotide sequence of DNA within a gene. This can alter protein
structure and function, leading to diseases or evolutionary changes. Mutations can occur
spontaneously or be caused by external mutagens such as radiation and chemicals.

2. Causes of Gene Mutation

Mutations are caused by three major factors:

1. Ionizing Radiation (X-rays, Gamma Rays, Radioactive Radiation)

2. Ultraviolet (UV) Radiation
3. Chemical Mutagens

A. Ionizing Radiation

1. Definition:

Ionizing radiation has high energy that can break DNA strands, causing severe genetic damage.

2. Sources:

• X-rays (used in medical imaging)

• Gamma rays (emitted by radioactive materials)
• Nuclear radiation (from atomic explosions or nuclear power plants)

3. Effects on DNA:

• Double-strand DNA breaks, which are difficult to repair.

• Point mutations, deletions, and chromosomal mutations.
• Increased risk of cancer (e.g., leukemia, thyroid cancer).
• High doses can cause cell death and radiation sickness.

B. Ultraviolet (UV) Radiation

1. Definition:

UV radiation from the sun or artificial sources (e.g., tanning beds) has lower energy than ionizing
radiation but can still cause mutations.
2. Mechanism of DNA Damage:

• UV light causes thymine dimers, where two thymine bases bond together incorrectly.
• This disrupts DNA replication and transcription, leading to mutations.

3. Effects on Health:

• Skin cancer (e.g., melanoma, basal cell carcinoma).

• Premature aging due to DNA damage in skin cells.
• Eye damage, including cataracts and retinal degeneration.

C. Chemical Mutagens

1. Definition:

Chemical mutagens alter DNA structure or base pairing, leading to mutations.

2. Examples of Chemical Mutagens:

• Alkylating Agents (e.g., Mustard Gas) – Modify DNA bases, causing mispairing.
• Nitrous Acid – Deaminates bases, leading to incorrect base pairing.
• Acridine Dyes – Insert themselves into DNA, causing frame-shift mutations.
• Reactive Oxygen Species (ROS) – Damage DNA and proteins, leading to cancer and
aging.

3. Effects on Health:

• Cancer (e.g., lung cancer from tobacco smoke, liver cancer from aflatoxins).
• Birth defects due to mutations in germ cells.
• Neurological disorders due to DNA damage in brain cells.

4. Summary

• Ionizing radiation causes double-strand breaks, increasing cancer risk.

• UV radiation forms thymine dimers, leading to skin damage and cancer.
• Chemical mutagens alter DNA structure, causing mispairing, frame-shift mutations,
and cancer.
• Gene mutations can be harmful (causing diseases like cancer), neutral, or beneficial
(contributing to evolution).
20.6.5 Sickle Cell Anemia and Phenylketonuria

1. Sickle Cell Anemia (SCA)

Definition:

Sickle cell anemia is a genetic blood disorder caused by a point mutation in the gene coding for the
beta-globin chain of hemoglobin (Hb). This mutation leads to abnormal hemoglobin (HbS), causing
red blood cells to become sickle-shaped instead of round.

Cause:

• A single base substitution in the HBB gene (chromosome 11).

• Glutamic acid (GAG) is replaced by valine (GTG) at position 6 of the beta-globin
chain.
• This changes hemoglobin structure, making red blood cells stiff and crescent-shaped.

Effects on the Body:

• Reduced oxygen transport, leading to fatigue and shortness of breath.

• Blocked blood flow, causing severe pain (sickle cell crisis).
• Organ damage (kidneys, spleen, liver, and brain).
• Increased risk of infections due to spleen dysfunction.

Symptoms:

• Severe joint and body pain (pain crisis).

• Pale skin (anemia), fatigue, and weakness.
• Jaundice (yellowing of skin and eyes).
• Swollen hands and feet due to poor circulation.
• Delayed growth and puberty in children.

Treatment:

• Blood transfusions to increase normal RBC count.

• Pain relievers and hydration therapy to prevent crises.
• Bone marrow transplant (potential cure).
• Hydroxyurea (drug) to increase fetal hemoglobin (HbF) production.

2. Phenylketonuria (PKU)
Definition:

Phenylketonuria (PKU) is a metabolic disorder caused by a gene mutation that affects the breakdown
of phenylalanine (Phe), an amino acid. If untreated, it leads to brain damage and intellectual
disability.

Cause:

• Mutation in the PAH gene (phenylalanine hydroxylase enzyme) on chromosome 12.

• Phenylalanine cannot be converted into tyrosine, leading to its toxic accumulation in
the brain.

Effects on the Body:

• Brain damage and mental retardation due to toxic buildup.

• Impaired growth and motor skills.
• Behavioral and psychiatric problems.
• Seizures and tremors due to nervous system damage.

Symptoms:

• Lighter skin, hair, and eyes (due to low melanin).

• Musty odor in breath, skin, and urine (due to excess phenylalanine).
• Small head size (microcephaly).
• Hyperactivity and learning disabilities.

Treatment:

• Low-phenylalanine diet (avoid meat, dairy, nuts, and aspartame).

• Special formula (Lofenalac) for infants.
• Tyrosine supplements to compensate for deficiency.

Summary

• Sickle cell anemia is a blood disorder caused by abnormal hemoglobin (HbS), leading
to sickle-shaped RBCs, pain, and organ damage.
• Phenylketonuria (PKU) is a metabolic disorder where phenylalanine accumulates,
leading to brain damage and intellectual disability.
• Both diseases are autosomal recessive and require early diagnosis and lifelong
management.

Comparison of Sickle Cell Anemia and Phenylketonuria

1. Cause:

• Sickle Cell Anemia (SCA) is caused by a point mutation in the HBB gene on
chromosome 11, leading to abnormal hemoglobin (HbS).
• Phenylketonuria (PKU) is caused by a mutation in the PAH gene on chromosome 12,
resulting in a defective enzyme, phenylalanine hydroxylase.

2. Effect on Protein:

• In SCA, the mutation causes abnormal hemoglobin (HbS), making red blood cells
rigid and sickle-shaped.
• In PKU, the mutation prevents phenylalanine hydroxylase from breaking down
phenylalanine, leading to toxic accumulation in the brain.

3. Symptoms:

• SCA symptoms include pain crises, anemia, jaundice, and organ damage due to
blocked blood flow.
• PKU symptoms include mental retardation, light skin, seizures, hyperactivity, and
musty odor in urine.

4. Mode of Inheritance:

• Both SCA and PKU are autosomal recessive disorders, meaning a child must inherit
defective genes from both parents to develop the disease.

5. Treatment:

• SCA treatment includes blood transfusions, hydroxyurea (to increase fetal

hemoglobin), and bone marrow transplants.
• PKU treatment involves a low-phenylalanine diet, special infant formulas (like
Lofenalac), and tyrosine supplements.