🧬 Genetic mutations are permanent changes in the DNA sequence. They may be germline (inherited, present in all cells) or somatic (acquired, restricted to certain tissues, e.g. cancer). Mutations are a major source of genetic diversity but also underlie many human diseases.

🧾 Types of Genetic Mutations

Point Mutations 🎯 :
- Single nucleotide change.
- Types:
  - Missense → one amino acid replaced by another (e.g. sickle cell anaemia, HBB gene).
  - Nonsense → premature stop codon → truncated protein (e.g. Duchenne muscular dystrophy).
  - Silent → no amino acid change (due to codon redundancy) but may affect splicing or mRNA stability.
Insertions & Deletions (Indels) ➕➖ :
- Extra or missing nucleotides.
- If not multiple of 3 → frameshift → altered reading frame (e.g. Tay-Sachs disease).
Copy Number Variations (CNVs) 📊 :
- Large segments duplicated or deleted (e.g. Charcot-Marie-Tooth disease type 1A).
Chromosomal Mutations 🧩 :
- Deletions (Cri-du-chat, 5p deletion).
- Duplications.
- Inversions.
- Translocations (Philadelphia chromosome in CML: t(9;22)).
- Aneuploidy (trisomy 21 → Down syndrome; monosomy X → Turner syndrome).

⚠️ Causes of Mutations

Spontaneous :
- Replication errors (mismatch, slippage).
- Spontaneous base deamination/oxidation.
Induced :
- Radiation (UV → thymine dimers; X-rays → double-strand breaks).
- Chemicals (alkylating agents, tobacco carcinogens).
- Biological (retroviruses inserting into host genome).

📊 Consequences of Mutations

Beneficial 🌟 : e.g. CCR5-Δ32 mutation → resistance to HIV.
Neutral ⚖️ : Silent or non-coding variants with no effect on fitness.
Harmful ❌ : Disease-causing → cancer (p53 mutation), metabolic disorders, congenital syndromes.

🧪 Examples of Genetic Disorders

Single-Gene :
- Cystic fibrosis (CFTR mutations, ΔF508).
- Sickle cell disease (HBB missense mutation).
- Huntington’s disease (CAG trinucleotide repeat expansion, HTT gene).
Chromosomal :
- Down syndrome (trisomy 21).
- Turner syndrome (45,X).
- Klinefelter syndrome (47,XXY).
Complex / Multifactorial :
- Diabetes, heart disease, schizophrenia → polygenic + environmental influence.

🔍 Detection & Analysis

Genetic testing → PCR, Sanger sequencing, FISH, karyotyping, microarrays.
Next-Generation Sequencing (NGS) → high-throughput, used for cancer panels, rare disease diagnosis.
Whole exome/genome sequencing → research & clinical applications.

💉 Clinical Relevance

Personalised Medicine 🎯 :
- EGFR, KRAS, BRAF mutations → guide targeted cancer therapies.
- Pharmacogenomics (e.g. TPMT mutation → azathioprine toxicity).
Gene Therapy 🛠️ :
- CRISPR-Cas9 and viral vectors used to correct defective genes (e.g. in SCID).
Cancer 🔬 :
- Mutations in tumour suppressors (p53, BRCA1/2) and oncogenes (RAS, MYC) drive oncogenesis.
- Targeted therapies (imatinib in CML, PARP inhibitors in BRCA mutations).

📚 Summary

Genetic mutations may be point, indel, CNV, or chromosomal. They arise spontaneously or from environmental damage. Consequences range from neutral to beneficial to disease-causing. Understanding mutations is vital in genetics, oncology, pharmacology, and personalised medicine.

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Genetic Mutations