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AN74.1-4 | Patterns of Inheritance — Self-Directed Learning
CLINICAL SCENARIO
A 28-year-old woman from a village in Tamil Nadu is referred to MGMCRI antenatal OPD in her first trimester. Her elder child has sickle cell disease and her husband is worried about this baby. 'Doctor, will this child also be sick?' — How do you calculate the risk? Understanding Mendelian inheritance lets you give her a clear, evidence-based answer and appropriate genetic counselling.
WHY THIS MATTERS
Patterns of inheritance underpin genetic counselling for hundreds of single-gene disorders prevalent in India: sickle cell disease (tribal belts of Odisha, MP, Maharashtra), thalassaemia (Bengal, Gujarat, Punjab), haemophilia (X-linked), and Marfan syndrome (autosomal dominant). For a clinician, recognising the inheritance pattern from a three-generation pedigree tells you the recurrence risk before any genetic test is ordered.
RECALL
Before going further, recall:
• What is an allele? How does it differ from a gene?
• What is the difference between homozygous and heterozygous?
• What are chromosomes, and how many pairs does a normal human somatic cell have?
If any of these feel uncertain, spend 5 minutes reviewing your cell biology notes first.
Mendel's Laws and Monohybrid Inheritance
Law of Segregation: Each organism carries two alleles for each trait. During gamete formation (meiosis), the two alleles separate so each gamete receives only one allele.
Law of Independent Assortment: Alleles of different genes assort independently during gamete formation (applies to genes on different chromosomes).
Key Terminology
- Dominant allele (A): expressed in both AA and Aa genotypes
- Recessive allele (a): expressed only in aa genotype
- Carrier: heterozygous (Aa) for a recessive disorder — clinically unaffected but can transmit the allele
Autosomal Dominant (AD)
- One abnormal allele is sufficient to cause disease
- Affected individuals in every generation (vertical transmission)
- Both sexes equally affected
- Unaffected parents do NOT pass the disease (unless new mutation)
- 50% offspring risk if one parent is affected (Aa × aa)
- Examples: Marfan syndrome, Huntington's disease, achondroplasia, familial hypercholesterolaemia, neurofibromatosis type 1
Autosomal Recessive (AR)
- Two abnormal alleles needed (aa)
- Parents are usually carriers (Aa) — clinically normal
- Carrier × Carrier cross (Aa × Aa): 25% affected, 50% carrier, 25% normal
- Consanguinity increases risk significantly — important in India where cousin marriages are common in some communities (Andhra, Tamil Nadu, Karnataka)
- Horizontal transmission: siblings affected, parents and grandparents unaffected
- Examples: sickle cell disease, thalassaemia, PKU, cystic fibrosis, congenital adrenal hyperplasia
SELF-CHECK
A. 10%
B. 25%
C. 50%
D. 75%
Reveal Answer
Answer: A.
X-Linked Inheritance
X-linked Recessive
- Gene on X chromosome; males (XY) have only one X → single abnormal allele = affected
- Females (XX) need two abnormal alleles to be affected; carriers (X^A X^a) are usually unaffected
- Carrier mother × normal father: 50% of sons affected, 50% of daughters carriers
- No father-to-son transmission (fathers give Y to sons)
- Predominantly affects males; females are carriers
- Examples: haemophilia A & B, Duchenne muscular dystrophy, G6PD deficiency, colour blindness, Fabry disease
X-linked Dominant
- One abnormal allele on X causes disease in both males and females
- Affected father → ALL daughters affected, NO sons affected
- Affected mother (heterozygous) → 50% sons, 50% daughters affected
- Rarer: hypophosphataemia (Vitamin D-resistant rickets), Rett syndrome (lethal in males → mostly females affected)
Pedigree Analysis Tips
1. If all affected individuals are male → suspect X-linked recessive
2. If father-to-son transmission seen → autosomal (not X-linked)
3. If consecutive generations affected → autosomal dominant or X-linked dominant
4. If siblings affected but parents normal → autosomal recessive
5. Consanguinity symbol (double horizontal line) → think AR
CLINICAL PEARL
India-specific consanguinity risk: In South India, first-cousin marriages increase the coefficient of relationship (r = 1/8), dramatically raising the probability that two carriers of the same AR disorder marry. In communities with high thalassaemia carrier frequency (e.g., Sindhi, Gujarati, Bengali — carrier rate 3–17%), routine premarital screening + genetic counselling is standard of care. Under the MTP Act 2021, termination is permitted for foetal anomalies at any gestational age with appropriate approvals.
REFLECT
KEY TAKEAWAYS
Core Take-Aways
- AD: Vertical transmission, 50% risk, both sexes — Marfan, Huntington, achondroplasia
- AR: Horizontal transmission, 25% risk, consanguinity risk, carriers unaffected — thalassaemia, sickle cell
- XLR: Males affected, females carriers, no father-to-son — haemophilia, DMD, G6PD
- XLD: Rare; father gives to ALL daughters, NO sons — hypophosphataemia
- Pedigree analysis: look for generation pattern, sex distribution, consanguinity
- In Indian practice: sickle cell (tribal), thalassaemia (coastal + plains), G6PD (widespread) are high-prevalence AR/XLR disorders requiring carrier screening