BiologyISC Class 12 · Principles of Inheritance and Variation

Pedigree Analysis and Mendelian Disorders: ISC Class 12 Biology

Updated 15 October 2026 · Fact-checked

Pedigree analysis traces a trait through several generations of a family using standard symbols, to decide whether it is dominant or recessive and autosomal or X-linked. Mendelian disorders are caused by a single gene: sickle-cell anaemia, thalassaemia and phenylketonuria are autosomal recessive; haemophilia and colour blindness are X-linked recessive.

Two unaffected parents have an affected child, so the trait must be recessive and both parents are carriers.

Illustration drawn for QuestionBuddy.

Understand Pedigree Analysis and Mendelian Disorders

Why pedigrees. Controlled crosses cannot be made in humans, so geneticists study family histories. The analysis of a trait over several generations of a family is pedigree analysis. ISC expects you to draw a pedigree from a description and interpret one.

Standard symbols. Square = male; circle = female; diamond = sex unspecified; shaded symbol = affected; half-shaded or central dot = carrier (heterozygote); horizontal line between a male and female = mating; double line = consanguineous mating; vertical line down to a horizontal bar with offspring hanging from it = children (siblings) in birth order; generations numbered I, II, III; individuals numbered 1, 2, 3 in each generation.

Reading a pedigree: four questions.
1. Do two unaffected parents have an affected child? Then the trait is recessive (both parents are carriers).
2. Does every affected child have at least one affected parent, and do two affected parents have an unaffected child? Then it is dominant.
3. Is it mostly in males, passed from carrier mothers to sons, never father to son? Then X-linked recessive.
4. Are males and females equally affected, and is father-to-son transmission seen? Then autosomal.
Examples NCERT uses: myotonic dystrophy (autosomal dominant), sickle-cell anaemia (autosomal recessive).

Mendelian disorders: caused by alteration or mutation in a single gene; inherited according to Mendel's principles; may be dominant or recessive, autosomal or sex-linked. Common ones: haemophilia, cystic fibrosis, sickle-cell anaemia, colour blindness, phenylketonuria, thalassaemia.

Sickle-cell anaemia (autosomal recessive). Alleles HbA and HbS. HbAHbA normal; HbAHbS apparently unaffected carriers (sickle-cell trait; 50% chance of passing HbS to each child); HbSHbS diseased.

Biochemical cause: glutamic acid (Glu) is replaced by valine (Val) at the sixth position of the β-globin chain of haemoglobin.
Genetic cause: a single base substitution in the sixth codon of the β-globin gene, GAG → GUG (in mRNA terms). In DNA this is A → T: a purine replaced by a pyrimidine, i.e. a transversion type of point mutation (substitution).
The mutant haemoglobin polymerises under low oxygen tension, changing RBCs from biconcave discs to elongated sickle shapes.

Thalassaemia (autosomal recessive). Mutation or deletion reduces the rate of synthesis of one of the globin chains, forming abnormal haemoglobin and causing anaemia. α-thalassaemia: two closely linked genes HBA1 and HBA2 on chromosome 16 of each parent (four genes in all); the more genes affected, the less α-globin. β-thalassaemia: single gene HBB on chromosome 11 of each parent. Thalassaemia is a quantitative problem (too few globin molecules); sickle-cell anaemia is qualitative (wrongly functioning globin).

Phenylketonuria (PKU) (autosomal recessive; an inborn error of metabolism). The affected person lacks the enzyme that converts phenylalanine to tyrosine. Phenylalanine accumulates and is converted into phenylpyruvic acid and other derivatives; their accumulation in the brain causes mental retardation, and they are excreted in urine because of poor absorption by the kidney. PKU also shows pleiotropy: one gene, several effects, including reduced hair and skin pigmentation.

Haemophilia and colour blindness are X-linked recessive (see sex-linked inheritance).

Point mutations (ISC). Transition: purine → purine or pyrimidine → pyrimidine (A ↔ G, C ↔ T). Transversion: purine ↔ pyrimidine (A → T, G → C). Frame-shift: insertion or deletion of bases that shifts the reading frame. Mutations may be spontaneous or induced by mutagens such as UV radiation.

Mendelian versus chromosomal disorders. Mendelian: single-gene mutation, follows Mendelian ratios, traced by pedigree. Chromosomal: absence, excess or abnormal arrangement of chromosomes, e.g. Down's syndrome (trisomy 21, described by Langdon Down, 1866), Klinefelter's syndrome (47, XXY, sterile male with some feminine development), Turner's syndrome (45, X0, sterile female with rudimentary ovaries).

Draw and label: autosomal recessive pedigree. Checklist: generation I, two unshaded carriers (central dots) joined by a mating line; generation II, four children: one shaded (affected), two dotted (carriers), one plain; Roman numerals at the left; a key to symbols.

Pedigree Analysis and Mendelian Disorders: key facts

Carrier × carrier (autosomal recessive): $A a \times A a \to \frac{1}{4} AA : \frac{1}{2} A a : \frac{1}{4} aa$; Of the unaffected children, 2/3 are carriers.
Affected × carrier: $aa \times A a \to \frac{1}{2} A a : \frac{1}{2} aa$; Each child has a 1/2 chance of being affected.
Independent children: $P (all n normal) = (\frac{3}{4})^{n}; P (at least one affected) = 1 - (\frac{3}{4})^{n}$; For two carrier parents.
Sickle-cell mutation: $codon 6: GAG \to GUG; Glu \to Val at position 6 of β -globin$; A to T in DNA: transversion.
Types of point mutation: $transition: purine \leftrightarrow purine; transversion: purine \leftrightarrow pyrimidine$; Frame-shift: insertion or deletion.

How to answer Pedigree Analysis and Mendelian Disorders questions

ISC asks you to read or draw a pedigree, give genotypes of named members, calculate probabilities, and explain the biochemical basis of disorders.

1Classify the disorder: autosomal recessive (sickle-cell, thalassaemia, PKU) or X-linked recessive (haemophilia, colour blindness). Do not write XY genotypes for an autosomal disorder.
2In a pedigree, find an affected child of unaffected parents: this proves the trait is recessive and both parents are carriers.
3Assign genotypes to everyone you can: affected = aa; parents of an affected child = at least Aa; children of an aa parent = at least Aa.
4For probabilities, use a Punnett square; for an unaffected sibling of an affected child, use 2/3 for being a carrier.
5For several children, multiply independent probabilities.
6For 'biochemical reason', name the protein, the position and both amino acids; for the mutation type, name substitution and transversion.

Pedigree Analysis and Mendelian Disorders in real life

The idea, met in an everyday situation. Answer the question in your own words, then compare with the model answer. The one-line hook is what to remember.

Premarital carrier screening for thalassaemia

Suppose two young people from a community where thalassaemia is common plan to marry. Both are healthy, but blood tests show that each is a carrier of β-thalassaemia.

What is the risk for each child, and what options could a genetic counsellor discuss?

Try it first, then show the solutionSolution

β-thalassaemia is autosomal recessive; both partners are carriers (Tt).
Tt × Tt gives TT : Tt : tt = 1 : 2 : 1, so each child has a 1/4 chance of thalassaemia, 1/2 of being a carrier and 1/4 of being unaffected and not a carrier.
The risk is the same for every pregnancy; it does not 'use up' after one affected child.
The counsellor can explain this risk, prenatal testing such as amniocentesis to check the foetus, and the support available, so that the couple can make an informed decision.

Answer: Each child has a 1/4 risk of thalassaemia and 1/2 chance of being a carrier; counselling and prenatal diagnosis help the couple decide.

Memory hook: Two healthy carriers: one in four, every time.

Tricks to remember Pedigree Analysis and Mendelian Disorders

Short memory aids. Say each one aloud once, then use it on a question the same day.

Hidden in parents = recessive
If the trait hides in both parents and pops out in a child, it is recessive.
Use it when: First test when reading a pedigree.
Sickle swap: G to V at six
'Glu Goes, Val Visits' at position 6 of β.
Use it when: Biochemical basis of sickle-cell anaemia.
Thala = too little, Sickle = wrong shape
Thalassaemia: quantity problem. Sickle-cell: quality problem.
Use it when: Comparing the two haemoglobin disorders.

Pedigree Analysis and Mendelian Disorders: solved examples

Ordered from board level to HOTS. Try each one before you open the solution.

Example 1: Biochemical basis of sickling · 2 marks · Short answerBoard level

Give the biochemical reason for sickle-cell anaemia and explain why the RBCs become sickle-shaped.

Try it first, then show the solutionSolution

Glutamic acid is replaced by valine at the sixth position of the β-globin chain of haemoglobin, due to the change GAG → GUG in the sixth codon (1 mark).
The mutant haemoglobin polymerises under low oxygen tension, distorting the RBC from a biconcave disc into an elongated sickle shape (1 mark).

Answer: Glu → Val at position 6 of β-globin; HbS polymerises at low oxygen and deforms RBCs.

Example 2: PKU · 2 marks · Short answerBoard level

Explain why phenylketonuria leads to mental retardation and why phenylpyruvic acid appears in the urine.

Try it first, then show the solutionSolution

The affected person lacks the enzyme that converts phenylalanine to tyrosine; phenylalanine accumulates and is converted into phenylpyruvic acid and other derivatives, which accumulate in the brain and cause mental retardation (1 mark).
These derivatives are poorly absorbed by the kidney and so are excreted in urine (1 mark).

Answer: Missing enzyme → phenylalanine and phenylpyruvic acid build up in the brain; poor kidney reabsorption puts them in urine.

Example 3: Sickle-cell family · 3 marks · Short answerHarder board level

Suppose a man who is a carrier of sickle-cell anaemia has a son with the disease. (a) Give the possible genotypes of the son's mother. (b) Show by a Punnett square the outcome if she is also a carrier. (c) Which kind of point mutation causes this disorder? Explain what that kind involves. (A family of this kind was asked about in 2024.)

Try it first, then show the solutionSolution

(a) The son is HbSHbS, so he received HbS from each parent; the mother is HbAHbS (carrier) or HbSHbS (affected) (1 mark).
(b) HbAHbS × HbAHbS → HbAHbA : HbAHbS : HbSHbS = 1 : 2 : 1; each child has a 1/4 chance of disease (1 mark).
(c) Substitution (point mutation); specifically a transversion: a purine (A) in the DNA is replaced by a pyrimidine (T) (1 mark).

Answer: (a) HbAHbS or HbSHbS. (b) 1 : 2 : 1, ¼ affected. (c) Substitution by transversion (purine → pyrimidine).

Example 4: Quantitative or qualitative · 3 marks · Short answerHarder board level

Compare sickle-cell anaemia and thalassaemia: mode of inheritance, nature of the defect, and genes involved.

Try it first, then show the solutionSolution

Both are autosomal recessive blood disorders (½ mark).
Sickle-cell: a qualitative defect, an incorrectly functioning β-globin (Glu → Val); thalassaemia: a quantitative defect, too few globin chains synthesised (1 mark).
Thalassaemia genes: α-type, HBA1 and HBA2 on chromosome 16 (four genes in all); β-type, HBB on chromosome 11; sickle-cell involves the β-globin gene (1½ marks).

Answer: Both autosomal recessive; sickle-cell qualitative (β-globin Glu→Val), thalassaemia quantitative (HBA1/HBA2 on 16 or HBB on 11).

Example 5: Reading a pedigree · 4 marks · Short answerHarder board level

In a pedigree, two unaffected parents (I-1, I-2) have four children: II-1 (male, affected), II-2 (female, unaffected), II-3 (female, affected), II-4 (male, unaffected). (a) Is the trait dominant or recessive? (b) Is it autosomal or X-linked? (c) Give the genotypes of I-1 and II-3. (d) What is the chance that II-2 is a carrier?

Try it first, then show the solutionSolution

(a) Recessive: unaffected parents have affected children, so both carry a hidden allele (1 mark).
(b) Autosomal: an affected daughter (II-3) has an unaffected father; for an X-linked recessive trait her father would have to be affected (1 mark).
(c) I-1: Aa; II-3: aa (1 mark).
(d) II-2 is unaffected, so she is AA or Aa; among unaffected children of Aa × Aa, 2 of 3 are Aa: chance 2/3 (1 mark).

Answer: (a) Recessive (b) autosomal (c) Aa, aa (d) 2/3.

Example 6: Risk for a sibling's child · 3 marks · Short answerHOTS / competency

Suppose II-2 in the previous pedigree (unaffected sister of two affected siblings) marries a man known to be a carrier of the same disorder. (a) How likely is it that their first-born will be affected? (b) If they have three children, what is the probability that at least one is affected, assuming II-2 is in fact a carrier?

Try it first, then show the solutionSolution

(a) P(II-2 is Aa) = 2/3; P(child aa from Aa × Aa) = 1/4; product = 2/3 × 1/4 = 1/6 (1½ marks).
(b) Given both are carriers, P(a child is normal) = 3/4; P(all three normal) = (3/4)³ = 27/64 (1 mark).
P(at least one affected) = 1 − 27/64 = 37/64 ≈ 0.58 (½ mark).

Answer: (a) 1/6. (b) 37/64.

Where students lose marks in Pedigree Analysis and Mendelian Disorders

The slips examiners see most often, and what to write instead.

Mistake: Treating thalassaemia as sex-linked
In 2024 examiners reported that candidates gave an XY genotype for an affected male in a thalassaemia pedigree, as if it were haemophilia.
Wrong working
Affected male: XᵗY.
Right working
Affected male: tt (homozygous recessive, autosomal).
Do this: Learn which disorders are autosomal (sickle-cell, thalassaemia, PKU) and which X-linked (haemophilia, colour blindness).
Usually costs: 1 mark.
Mistake: Describing cell shape instead of the biochemical reason
In 2024 examiners found answers describing sickle-shaped cells, or 'valine replaced by glutamic acid' without mentioning the β-chain.
Do this: Write: glutamic acid replaced by valine at the sixth position of the β-globin chain.
Usually costs: 1 mark.
Mistake: Naming 'point mutation' without the type
Examiners (2024) noted candidates repeated 'point mutation' without naming substitution or transversion.
Do this: Write: substitution; transversion, a purine replaced by a pyrimidine (A → T).
Usually costs: 1 mark.
Mistake: Leaving the mother's genotype out of the Punnett square
Examiners (2024) saw Punnett squares without the mother's genotype stated.
Do this: Label both parents' genotypes and gametes above the square.
Usually costs: ½ to 1 mark.

Exam tips

Use HbA/HbS notation for sickle-cell anaemia; examiners accept it and it shows understanding.
Always include a key when drawing a pedigree.
Give the chromosome numbers for thalassaemia genes: HBA1, HBA2 on 16; HBB on 11.
Use 2/3 for the carrier chance of an unaffected sibling of an affected person.
In disorder answers, give cause, inheritance pattern and one symptom.

Practice questions on Pedigree Analysis and Mendelian Disorders

Write each answer on paper first. Open the hint only if you are stuck, and the answer only when you have finished.

Q1 · 1 mark · MCQBoard level
In pedigree symbols, a shaded circle represents:
(a) an affected male (b) an affected female (c) a carrier female (d) a female of unknown sex
Hint
Circle = female; shaded = affected.
Answer
(b) An affected female.
Q2 · 2 marks · Short answerBoard level
Distinguish between a Mendelian disorder and a chromosomal disorder, with one example of each.
Hint
One gene versus whole chromosomes.
Answer
A Mendelian disorder is caused by a mutation in a single gene and follows Mendelian inheritance (sickle-cell anaemia, PKU, haemophilia). A chromosomal disorder is caused by absence, excess or abnormal arrangement of chromosomes (Down's syndrome, trisomy 21; Turner's syndrome, 45 X0).
Q3 · 1 mark · Assertion-reasonHarder board level
Assertion (A): A person with sickle-cell trait (HbAHbS) can pass the disease allele to children.
Reason (R): Heterozygotes are apparently unaffected but have a 50% probability of transmitting HbS to each child.
(a) Both A and R are true and R is the correct explanation of A.
(b) Both A and R are true but R is not the correct explanation of A.
(c) A is true but R is false.
(d) A is false but R is true.
Hint
Carrier.
Answer
(a).
Q4 · 2 marks · Short answerHarder board level
Classify each change as a transition, transversion or frame-shift: (a) A → G, (b) C → A, (c) deletion of one base, (d) T → C.
Hint
Purines are A and G; pyrimidines C and T.
Answer
(a) Transition (purine → purine). (b) Transversion (pyrimidine → purine). (c) Frame-shift. (d) Transition (pyrimidine → pyrimidine).
Q5 · 2 marks · Short answerHarder board level
A pedigree shows thalassaemia in a family. Write the genotype of an affected male, and explain why writing XᵗY would be wrong.
Hint
Which chromosome carries the gene?
Answer
tt (homozygous recessive). Thalassaemia is autosomal recessive: the genes lie on autosomes (chromosome 16 for α, 11 for β), not on the X, so an XY genotype applies only to sex-linked traits such as haemophilia.
Q6 · 2 marks · Short answerHarder board level
An affected woman with an autosomal recessive disorder marries a carrier man. What fraction of their children will be (a) affected, (b) carriers, (c) completely free of the allele?
Hint
aa × Aa.
Answer
aa × Aa → 1/2 Aa, 1/2 aa. (a) 1/2 affected. (b) 1/2 carriers. (c) 0.
Q7 · 3 marks · Short answerHOTS / competency
Suppose a disorder appears in every generation of a family; every affected child has an affected parent; and two affected parents have one unaffected daughter. (a) Is the trait dominant or recessive? (b) Give the genotypes of the two affected parents. (c) What is the chance that their next child is affected?
Hint
An unaffected child of two affected parents.
Answer
(a) Dominant: an unaffected child from two affected parents means both carry a hidden normal (recessive) allele. (b) Both Aa. (c) Aa × Aa gives 3/4 with at least one A, so 3/4 affected.
Q8 · 3 marks · Case-basedHOTS / competency
Read and answer.
Suppose a newborn screening programme finds a baby with high phenylalanine in the blood. Neither parent shows the condition.
(a) Name the disorder and its mode of inheritance. (1)
(b) What are the genotypes of the parents and the chance that their next child is affected? (1)
(c) Why is this disorder an example of pleiotropy? (1)
Hint
Inborn error of metabolism.
Answer
(a) Phenylketonuria; autosomal recessive. (b) Both parents are carriers (Pp); each child has a 1/4 chance. (c) A single gene mutation produces several effects: mental retardation, reduced hair and skin pigmentation, and phenylpyruvic acid in urine.

Test your recall

Answer in your head or on paper first, then open the card. Pulling an answer out of memory makes it stick far better than re-reading.

1.What is the genotype of a sickle-cell carrier?Show answer
HbAHbS.
2.Which enzyme function is missing in PKU?Show answer
Conversion of phenylalanine to tyrosine.
3.On which chromosome is the HBB gene?Show answer
Chromosome 11.
4.Give an example of an autosomal dominant trait from NCERT's pedigree figure.Show answer
Myotonic dystrophy.
5.What is a transversion?Show answer
A point mutation in which a purine is replaced by a pyrimidine or vice versa.
6.What is the karyotype in Klinefelter's syndrome?Show answer
47, XXY.

Pedigree Analysis and Mendelian Disorders: frequently asked questions

What is pedigree analysis?

The study of a trait through several generations of a family, drawn as a family tree with standard symbols, to find whether it is dominant or recessive and autosomal or sex-linked.

Why is sickle-cell anaemia called a point mutation disorder?

It results from a single base substitution (GAG to GUG) in the sixth codon of the β-globin gene.

How is thalassaemia different from sickle-cell anaemia?

Thalassaemia is a quantitative defect (too few globin chains); sickle-cell anaemia is qualitative (an abnormal globin).

How can you tell a recessive trait from a pedigree?

Two unaffected parents have an affected child, showing that both carry a hidden recessive allele.

What are Mendelian disorders?

Disorders caused by mutation in a single gene and inherited according to Mendel's principles, such as haemophilia, sickle-cell anaemia, colour blindness, PKU and thalassaemia.