Genetic Mutation and Disorders

BiologyPrinciples of Inheritance and VariationFor NEET aspirants

Genetic mutation and disorders link changes in DNA to inherited diseases in humans. This page covers mutation, chromosomal aberrations, point and frame-shift mutations and mutagens. It then covers pedigree analysis, the Mendelian disorders (colour blindness, haemophilia, sickle-cell anaemia, phenylketonuria and thalassemia) and the chromosomal disorders (Down's, Klinefelter's and Turner's syndromes), as in the NCERT Class 12 chapter Principles of Inheritance and Variation. NEET often asks the sickle-cell base change, karyotypes, sex-linked inheritance and pedigree patterns of genetic mutation and disorders.

On this page1Mutation2Pedigree analysis3Mendelian disorders4Colour blindness5Haemophilia6Sickle-cell anaemia7Phenylketonuria8Thalassemia9Chromosomal disorders10Syndromes11Exam essentials12Quick revision13Solved examples14Practice

Key Points at a Glance

★ Must learn Mutation: alteration of DNA sequences, changing the genotype and the phenotype; with recombination, a source of variation.
Loss (deletion) or gain (insertion or duplication) of a DNA segment causes chromosomal aberrations, common in cancer cells.
★ Must learn Point mutation: change in a single base pair (sickle-cell anaemia). Insertion or deletion of base pairs causes frame-shift mutations.
Pedigree analysis: study of a trait through several generations of a family tree.
Colour blindness and haemophilia are sex-linked recessive; sickle-cell anaemia, phenylketonuria and thalassemia are autosomal recessive.
★ Must learn Sickle-cell anaemia: GAG → GUG at the sixth codon; Glu → Val at position 6 of the $β$ -globin chain.
Thalassemia is a quantitative problem (too few globin chains); sickle-cell anaemia is a qualitative one (faulty globin).
★ Must learn Aneuploidy: gain or loss of chromosomes from failed segregation of chromatids. Polyploidy: a whole extra set, from failed cytokinesis.
★ Must learn Down's: trisomy 21 (47). Klinefelter's: 47, XXY. Turner's: 45, X0.

1. Mutation

★ Very important Mutation: a phenomenon that results in alteration of DNA sequences, and consequently in changes in the genotype and the phenotype of an organism. Besides recombination, mutation is another phenomenon that leads to variation in DNA.

One DNA helix runs continuously from one end to the other in each chromatid, in a highly supercoiled form.
So the loss (deletion) or gain (insertion or duplication) of a segment of DNA alters the chromosome.
Genes are located on chromosomes, so alteration in chromosomes results in abnormalities or aberrations.
★ Exam imp Chromosomal aberrations are commonly observed in cancer cells.
★ Exam imp Mutation can also arise from a change in a single base pair of DNA. This is a point mutation; a classical example is sickle-cell anaemia.
Deletions and insertions of base pairs of DNA cause frame-shift mutations.
Many chemical and physical factors induce mutations; they are called mutagens.
UV radiation can cause mutations in organisms: it is a mutagen.

Kind of change	What happens	Result or example
Deletion of a DNA segment	Loss of a segment of DNA	Chromosomal aberration
Insertion or duplication of a segment	Gain of a segment of DNA	Chromosomal aberration
Point mutation	Change in a single base pair	Sickle-cell anaemia
Deletion or insertion of base pairs	Base pairs lost or added	Frame-shift mutation

Memory Trick Point = one swap; frame-shift = add or drop. Swapping one base pair is a point mutation; adding or dropping base pairs shifts the reading frame.

Key idea

Mutation changes DNA itself, from a single base pair to whole segments of a chromosome.

2. Pedigree Analysis

The idea that disorders are inherited is old; it came from seeing certain features recur in families.
After Mendel's work was rediscovered, the inheritance of traits in human beings began to be analysed.
Controlled crosses, as in the pea plant, are not possible in human beings.
So the study of family history for a trait provides the alternative.
★ Exam imp Pedigree analysis: analysis of a trait in several generations of a family, in which the inheritance of the trait is shown in a family tree.
In human genetics, pedigree study is a strong tool to trace the inheritance of a specific trait, abnormality or disease.
Standard symbols are used to draw a pedigree:

Test yourself: hide labels

Figure 1: Symbols used in human pedigree analysis. Squares are males, circles females, filled symbols affected individuals, and a double line marks consanguineous mating.

Every feature of an organism is controlled by one gene or another, located on the DNA of a chromosome.
DNA is the carrier of genetic information and is passed from one generation to the next without change.
However, changes do occur occasionally; such an alteration in the genetic material is a mutation.
Many human disorders are associated with the inheritance of changed or altered genes or chromosomes.

Memory Trick Square = male, circle = female, diamond = sex unspecified. Filled means affected; a double line means mating between relatives.

Key idea

Since crosses cannot be made in humans, a family tree drawn with standard symbols is used to follow a trait.

3. Mendelian Disorders

★ Exam imp Genetic disorders fall broadly into two groups: Mendelian disorders and chromosomal disorders.
Mendelian disorders are mainly caused by alteration or mutation in a single gene.
They pass to the offspring by the principles of inheritance, and can be traced in a family by pedigree analysis.
Most common Mendelian disorders: haemophilia, cystic fibrosis, sickle-cell anaemia, colour blindness, phenylketonuria and thalassemia.
Mendelian disorders may be dominant or recessive; pedigree analysis shows which.
The trait may also be linked to a sex chromosome, as in haemophilia.
Such an X-linked recessive trait passes from a carrier female to her male progeny.

Figure 2: Representative pedigrees of (a) an autosomal dominant trait (example: myotonic dystrophy) and (b) an autosomal recessive trait (example: sickle-cell anaemia).

Tips and Tricks Reading a pedigree. Autosomal dominant: the trait appears in every generation, and every affected child has an affected parent. Autosomal recessive: unaffected parents can have an affected child, and both sexes are affected equally. X-linked recessive: mostly males are affected, and they receive the gene from carrier mothers.

NEET Focus Match the disorder to its pedigree type. Myotonic dystrophy is the example of an autosomal dominant trait; sickle-cell anaemia of an autosomal recessive trait; haemophilia and colour blindness are X-linked recessive. X-linked recessive traits pass from carrier mothers to sons, never from father to son.

3.1 Colour blindness

Colour blindness is a sex-linked recessive disorder.
It is due to a defect in either the red or the green cone of the eye, so the person fails to discriminate between red and green.
The defect is due to mutation in certain genes on the X chromosome.
★ Exam imp It occurs in about 8 per cent of males and only about 0.4 per cent of females.
This is because the genes for red-green colour blindness are on the X chromosome: males have only one X, while females have two.
The son of a woman who carries the gene has a 50 per cent chance of being colour blind.
The mother herself is not colour blind, because the gene is recessive and its effect is suppressed by her matching dominant normal gene.
A daughter will not normally be colour blind, unless her mother is a carrier and her father is colour blind.

3.2 Haemophilia

Haemophilia is a sex-linked recessive disease that has been widely studied.
It passes from an unaffected carrier female to some of her male progeny.
A single protein in the cascade of proteins involved in blood clotting is affected.
★ Exam imp So in an affected individual, a simple cut results in non-stop bleeding.
A heterozygous (carrier) female may transmit the disease to her sons.
A female haemophiliac is extremely rare: her mother must be at least a carrier, and her father must be haemophilic (unviable in the later stage of life).
The family pedigree of Queen Victoria shows many haemophilic descendants, as she was a carrier of the disease.

Colour blindness

Sex-linked recessive (X chromosome)
Defect in red or green cone
About 8% of males, 0.4% of females
Cannot tell red from green

Haemophilia

Sex-linked recessive (X chromosome)
A clotting-cascade protein affected
Carrier females pass it to sons
Non-stop bleeding from a simple cut

Memory Trick Mother carries, son suffers. In both colour blindness and haemophilia, an unaffected carrier mother passes the X-linked gene to half her sons. A daughter is affected only if the father is affected and the mother carries the gene.

3.3 Sickle-cell anaemia

Sickle-cell anaemia is an autosome-linked recessive trait.
It passes from parents to offspring when both partners are carriers (heterozygous) for the gene.
It is controlled by a single pair of alleles, Hb^A and Hb^S.
★ Exam imp Of the three possible genotypes, only individuals homozygous for Hb^S (Hb^S Hb^S) show the disease.
Heterozygous (Hb^A Hb^S) individuals appear unaffected, but they are carriers: there is a 50 per cent probability that they pass the mutant gene to their progeny. They show the sickle-cell trait.

Test yourself: hide labels

Figure 3: Red blood cells: (a) normal cells are biconcave discs; (b) in sickle-cell anaemia, many cells become elongated and sickle-shaped.

A single base is substituted at the sixth codon of the beta-globin gene: GAG becomes GUG (in the mRNA).
So glutamic acid (Glu) is replaced by valine (Val) at the sixth position of the beta-globin chain of haemoglobin.
The mutant haemoglobin polymerises under low oxygen tension.
The red blood cell changes shape from a biconcave disc to an elongated sickle-like structure.

Test yourself: hide labels

Figure 4: Amino acids of the relevant part of the

β

-chain of haemoglobin: (a) normal, with Glu at position 6; (b) sickle-cell, where GAG → GUG puts Val at position 6.

★ Very important Sickle-cell anaemia is a point mutation: GAG → GUG at the sixth codon, so Glu → Val at the sixth position of the $β$ -globin chain. Only Hb^S Hb^S individuals are diseased; Hb^A Hb^S carriers show the sickle-cell trait.

3.4 Phenylketonuria

Phenylketonuria is an inborn error of metabolism, inherited as an autosomal recessive trait.
★ Exam imp The affected individual lacks the enzyme that converts the amino acid phenylalanine into tyrosine.
So phenylalanine accumulates and is converted into phenylpyruvic acid and other derivatives.
Their accumulation in the brain results in mental retardation.
They are also excreted in urine, because of poor absorption by the kidney.

3.5 Thalassemia

Thalassemia is an autosome-linked recessive blood disease.
It passes from parents to offspring when both partners are unaffected carriers (heterozygous) for the gene.
The defect is due to either mutation or deletion, which reduces the rate of synthesis of one of the globin chains ( $α$ or $β$ ) of haemoglobin.
Abnormal haemoglobin molecules form, causing anaemia, which is characteristic of the disease.
Thalassemia is classified by the chain of the haemoglobin molecule that is affected.

Feature	$α$ thalassemia	$β$ thalassemia
Chain affected	Production of $α$ -globin chain	Production of $β$ -globin chain
Genes	Two closely linked genes, HBA1 and HBA2	A single gene, HBB
Location	Chromosome 16 of each parent	Chromosome 11 of each parent
Cause	Mutation or deletion of one or more of the four genes	Mutation of one or both genes
Severity	The more genes affected, the less $α$ -globin made	Depends on one or both genes mutated

Thalassemia

Quantitative problem
Too few globin molecules synthesised
Mutation or deletion
$α$ or $β$ chain affected

Sickle-cell anaemia

Qualitative problem
Incorrectly functioning globin synthesised
Single base substitution
$β$ chain: Glu → Val at position 6

Memory Trick Alpha on 16, Beta on 11.

α

thalassemia: two genes (HBA1, HBA2) on chromosome 16, so four copies in all.

β

thalassemia: one gene (HBB) on chromosome 11, so two copies. Thalassemia = Too few (quantity); sickle = Spoiled (quality).

Mendelian disorder	Inheritance	Defect	Key feature
Colour blindness	X-linked recessive	Red or green cone defect	Cannot discriminate red and green
Haemophilia	X-linked recessive	A clotting-cascade protein	Non-stop bleeding
Sickle-cell anaemia	Autosomal recessive	Glu → Val at position 6 of $β$ -globin	Sickle-shaped red blood cells
Phenylketonuria	Autosomal recessive	No enzyme to convert phenylalanine to tyrosine	Mental retardation; phenylpyruvic acid in urine
Thalassemia	Autosomal recessive	Reduced synthesis of $α$ or $β$ globin	Anaemia
Myotonic dystrophy	Autosomal dominant	Example used for an autosomal dominant pedigree	Appears in every generation

Quick Recall: tap to check

What fraction of the sons of a carrier mother are colour blind?

50 per cent.

Which genotype shows sickle-cell anaemia, and which shows the sickle-cell trait?

HbS HbS shows the disease; HbA HbS shows the trait (carrier).

Which enzyme activity is missing in phenylketonuria?

Conversion of phenylalanine into tyrosine.

Key idea

Mendelian disorders follow single-gene inheritance: X-linked recessive (colour blindness, haemophilia) or autosomal recessive (sickle-cell anaemia, phenylketonuria, thalassemia).

4. Chromosomal Disorders

Chromosomal disorders are caused by the absence, excess or abnormal arrangement of one or more chromosomes.
★ Exam imp Aneuploidy: the gain or loss of a chromosome (or chromosomes) caused by the failure of segregation of chromatids during the cell division cycle.
Examples: Down's syndrome results from the gain of an extra copy of chromosome 21; Turner's syndrome from the loss of an X chromosome in human females.
★ Exam imp Polyploidy: an increase in a whole set of chromosomes, caused by the failure of cytokinesis after the telophase stage of cell division. It is often seen in plants.
A normal human cell has 46 chromosomes (23 pairs): 22 pairs of autosomes and one pair of sex chromosomes.
Rarely, an individual has an additional copy of a chromosome, or lacks one chromosome of a pair.
These conditions are called trisomy and monosomy of a chromosome, respectively. They lead to very serious consequences.
Common examples of chromosomal disorders: Down's syndrome, Turner's syndrome and Klinefelter's syndrome.

Aneuploidy

Gain or loss of one or a few chromosomes
Failure of segregation of chromatids
Trisomy (2n + 1), monosomy (2n - 1)
Down's, Turner's syndromes

Polyploidy

Increase in a whole set of chromosomes
Failure of cytokinesis after telophase
Whole extra genome
Often seen in plants

Memory Trick Aneuploidy = chromatids fail; Polyploidy = cytokinesis fails. A few chromosomes too many or too few comes from faulty separation; a whole set extra comes from a cell that never divided its cytoplasm.

4.1 Down's syndrome

★ Exam imp Cause: an additional copy of chromosome number 21 (trisomy of 21), giving 47 chromosomes in all.
It was first described by Langdon Down (1866).
The affected individual is short statured, with a small round head, a furrowed tongue and a partially open mouth.
The palm is broad, with a characteristic palm crease.
Physical, psychomotor and mental development is retarded.

Test yourself: hide labels

Figure 5: A representative figure of an individual with Down's syndrome and the corresponding chromosomes. Note the three copies of chromosome 21 (trisomy 21).

4.2 Klinefelter's and Turner's syndromes

★ Exam imp Klinefelter's syndrome: caused by an additional copy of the X chromosome, giving the karyotype 47, XXY.
The individual has overall masculine development, but feminine development, such as development of the breasts (gynaecomastia), is also expressed.
Such individuals are sterile.
★ Exam imp Turner's syndrome: caused by the absence of one of the X chromosomes, giving 45 with X0.
Such females are sterile, as their ovaries are rudimentary; other features include a lack of other secondary sexual characters.

Test yourself: hide labels

Figure 6: Diagrammatic representation of genetic disorders due to sex chromosome composition in humans: (a) Klinefelter's syndrome (47, XXY); (b) Turner's syndrome (45, X0).

Disorder	Chromosomes	Total	Type	Key features
Down's syndrome	Trisomy 21	47	Autosomal trisomy	Short stature, small round head, furrowed tongue, partially open mouth, palm crease, retarded development
Klinefelter's syndrome	XXY	47	Sex chromosome trisomy	Masculine development with gynaecomastia; tall; sterile
Turner's syndrome	X0	45	Sex chromosome monosomy	Female; rudimentary ovaries; sterile; short; no other secondary sexual characters

These disorders can be easily studied by analysing karyotypes.

NEET Focus Count the chromosomes. Down's and Klinefelter's have 47; Turner's has 45. Down's is the only one of the three caused by an autosome (21); Klinefelter's is a male with an extra X, and Turner's is a female missing one X.

Quick Recall: tap to check

What is the karyotype in Klinefelter's syndrome?

47, XXY.

Which failure causes polyploidy?

Failure of cytokinesis after the telophase stage of cell division.

Who first described Down's syndrome, and in which year?

Langdon Down, in 1866.

Key idea

Chromosomal disorders come from too many or too few chromosomes: trisomy 21 (Down's), XXY (Klinefelter's) and X0 (Turner's).

5. Exam Essentials

Pairs to Match

Disorder or term	Matches with
Point mutation	Change in a single base pair; sickle-cell anaemia
Frame-shift mutation	Deletion or insertion of base pairs
UV radiation	Mutagen
Chromosomal aberrations	Commonly seen in cancer cells
Myotonic dystrophy	Autosomal dominant trait
Colour blindness	Red or green cone defect; X-linked recessive
Haemophilia	Clotting-cascade protein; Queen Victoria
Sickle-cell anaemia	GAG → GUG; Glu → Val at position 6
Phenylketonuria	Phenylalanine not converted to tyrosine
$α$ thalassemia	HBA1 and HBA2 on chromosome 16
$β$ thalassemia	HBB on chromosome 11
Aneuploidy	Failure of segregation of chromatids
Polyploidy	Failure of cytokinesis after telophase
Down's syndrome	Trisomy 21; Langdon Down, 1866
Klinefelter's syndrome	47, XXY; gynaecomastia
Turner's syndrome	45, X0; rudimentary ovaries

Exceptions

Sickle-cell anaemia is autosomal, not sex-linked, unlike haemophilia and colour blindness.
Only Hb^S Hb^S individuals are diseased; Hb^A Hb^S carriers are not.
A colour-blind daughter needs a carrier mother and a colour-blind father.
Carrier mothers of haemophilia or colour blindness are not affected themselves.
Thalassemia is a quantitative defect, unlike the qualitative defect of sickle-cell anaemia.
Down's syndrome involves an autosome; Klinefelter's and Turner's involve sex chromosomes.
Turner's syndrome has 45 chromosomes, unlike the 47 of Down's and Klinefelter's.
Polyploidy is often seen in plants, not as a common human disorder.

Numbers to Remember

Colour blindness: about 8 per cent of males and 0.4 per cent of females.
Son of a carrier mother: 50 per cent chance of colour blindness.
Sickle-cell: substitution at the sixth codon and the sixth amino acid of $β$ -globin.
$α$ thalassemia: chromosome 16, two genes, four copies in all; $β$ thalassemia: chromosome 11.
Normal human: 46 chromosomes = 22 pairs of autosomes + 1 pair of sex chromosomes.
Down's: 47 (trisomy 21); described in 1866. Klinefelter's: 47, XXY. Turner's: 45, X0.

Mendelian disorders

Mutation in a single gene
Follow Mendel's principles
Traced by pedigree analysis
Haemophilia, sickle-cell anaemia, phenylketonuria

Chromosomal disorders

Absence, excess or abnormal arrangement of chromosomes
Aneuploidy or polyploidy
Studied by karyotype analysis
Down's, Klinefelter's, Turner's

6. Quick Revision

Mutation alters DNA sequences, changing genotype and phenotype; with recombination, it causes variation.
Deletion, insertion or duplication of DNA segments causes chromosomal aberrations, common in cancer cells.
Point mutation: one base pair (sickle-cell); frame-shift: insertion or deletion of base pairs; UV is a mutagen.
Pedigree analysis follows a trait through generations; standard symbols; controlled crosses impossible in humans.
Genetic disorders: Mendelian (single gene) and chromosomal.
Myotonic dystrophy: autosomal dominant; sickle-cell anaemia: autosomal recessive.
Colour blindness: X-linked recessive; red or green cone; 8% males, 0.4% females.
Haemophilia: X-linked recessive; clotting protein; carrier mother to sons; Queen Victoria.
Sickle-cell: Hb^S Hb^S diseased; GAG → GUG, Glu → Val at 6; sickling under low oxygen tension.
Phenylketonuria: autosomal recessive; phenylalanine → tyrosine blocked; phenylpyruvic acid; mental retardation.
Thalassemia: autosomal recessive; $α$ (HBA1, HBA2, chr 16) and $β$ (HBB, chr 11); quantitative defect.
Aneuploidy: failed chromatid segregation; polyploidy: failed cytokinesis, common in plants.
Trisomy: one extra chromosome; monosomy: one missing.
Down's (trisomy 21, Langdon Down 1866); Klinefelter's (47, XXY, gynaecomastia, sterile); Turner's (45, X0, rudimentary ovaries, sterile).
Karyotype analysis identifies chromosomal disorders.

7. Solved Examples

Solved Example 1

Match List I with List II.
List I: A. Phenylketonuria, B. Haemophilia, C. Thalassemia, D. Turner's syndrome
List II: I. Reduced synthesis of a globin chain, II. 45, X0, III. Phenylalanine not converted to tyrosine, IV. A protein of the clotting cascade affected
Choose the correct answer:
(A) A-III, B-IV, C-I, D-II
(B) A-IV, B-III, C-I, D-II
(C) A-III, B-I, C-IV, D-II
(D) A-III, B-IV, C-II, D-I

Solution:

Answer: (A). Phenylketonuria-III, haemophilia-IV, thalassemia-I and Turner's syndrome-II.

Solved Example 2

Read the statements about sickle-cell anaemia.
A. It is an autosome-linked recessive trait.
B. Heterozygous individuals show the disease.
C. Glutamic acid is replaced by valine at the sixth position of the beta-globin chain.
D. The mutant haemoglobin polymerises under high oxygen tension.
E. It results from a single base substitution, GAG to GUG.
Choose the correct answer:
(A) A, C and E only
(B) A, B and C only
(C) B, D and E only
(D) A, C, D and E only

Solution:

Answer: (A). B is wrong: heterozygotes are carriers with the sickle-cell trait; only Hb^S Hb^S individuals are diseased. D is wrong: polymerisation happens under low oxygen tension.

Solved Example 3

Arrange the events leading to sickle-cell anaemia in the correct order.
A. Red blood cells become sickle-shaped
B. A single base change at the sixth codon of the beta-globin gene
C. Valine replaces glutamic acid at the sixth position
D. The mutant haemoglobin polymerises under low oxygen tension
Choose the correct answer:
(A) B, C, D, A
(B) C, B, D, A
(C) B, D, C, A
(D) B, C, A, D

Solution:

Answer: (A). The base change (B) alters the amino acid (C); the mutant haemoglobin polymerises (D), and the cells sickle (A).

Solved Example 4

A woman who carries the gene for colour blindness marries a man with normal vision. What fraction of their sons is expected to be colour blind?
(A) None
(B) 1/4
(C) 1/2
(D) All

Solution:

Answer: (C). Each son gets his X from the mother, who has one normal and one mutant X, so each son has a 50 per cent chance. Daughters get a normal X from the father, so none are colour blind.

Solved Example 5

Which of the following is NOT correct?
(A) Klinefelter's syndrome has the karyotype 47, XXY
(B) Turner's syndrome individuals are sterile females
(C) Down's syndrome is caused by monosomy of chromosome 21
(D) Polyploidy is often seen in plants

Solution:

Answer: (C). Down's syndrome is caused by trisomy of chromosome 21, an additional copy.

Solved Example 6

Statement I: Thalassemia is a quantitative problem of synthesising too few globin molecules.
Statement II:

β

thalassemia is controlled by two closely linked genes on chromosome 16.
(A) Both Statement I and Statement II are correct
(B) Statement I is correct but Statement II is incorrect
(C) Statement I is incorrect but Statement II is correct
(D) Both Statement I and Statement II are incorrect

Solution:

Answer: (B). Statement II describes $α$ thalassemia (HBA1, HBA2 on chromosome 16). $β$ thalassemia is controlled by the single gene HBB on chromosome 11.

8. Practice Questions

Practice Questions

Match List I with List II.
List I: A. Down's syndrome, B. Klinefelter's syndrome, C. Colour blindness, D. Myotonic dystrophy
List II: I. Autosomal dominant, II. Gynaecomastia, III. Trisomy 21, IV. X-linked recessive
(A) A-III, B-II, C-IV, D-I (B) A-II, B-III, C-IV, D-I (C) A-III, B-II, C-I, D-IV (D) A-III, B-IV, C-II, D-IAnswer: (A). Down's-trisomy 21, Klinefelter's-gynaecomastia, colour blindness-X-linked recessive, myotonic dystrophy-autosomal dominant.
Read the statements.
A. Aneuploidy results from failure of segregation of chromatids.
B. Polyploidy results from failure of cytokinesis after telophase.
C. Frame-shift mutations are caused by a single base substitution.
D. UV radiation is a mutagen.
Choose the correct answer: (A) A, B and D only (B) A and C only (C) B, C and D only (D) A, B, C and DAnswer: (A). C is wrong: frame-shift mutations are caused by deletions or insertions of base pairs.
Which disorder is caused by the lack of an enzyme that converts phenylalanine into tyrosine? (A) Sickle-cell anaemia (B) Phenylketonuria (C) Thalassemia (D) HaemophiliaAnswer: (B). Phenylalanine accumulates and forms phenylpyruvic acid, which affects the brain.
Which of the following is NOT a symptom of Down's syndrome? (A) Small round head (B) Furrowed tongue (C) Tall stature (D) Palm creaseAnswer: (C). Individuals with Down's syndrome are short statured; tall stature is a feature of Klinefelter's syndrome.
Both parents are carriers of sickle-cell anaemia (Hb^A Hb^S). What is the probability that their child is a carrier like them?Answer: 1/2. The children are 1/4 Hb^A Hb^A, 1/2 Hb^A Hb^S and 1/4 Hb^S Hb^S.
Arrange the chromosome numbers in increasing order: A. Normal human cell, B. Turner's syndrome, C. Down's syndrome.
(A) B, A, C (B) A, B, C (C) B, C, A (D) C, A, BAnswer: (A). Turner's 45, normal 46, Down's 47.
Design a pedigree for an X-linked recessive trait such as haemophilia. What pattern does it show?Answer: Draw an unaffected father (open square) and a carrier mother (open circle). Among their children, about half the sons are affected (filled squares), and the daughters are unaffected, though half are carriers. The trait passes from carrier mothers to sons, mostly males are affected, and it never passes from father to son.
What is pedigree analysis? Suggest how such an analysis can be useful.Answer: Pedigree analysis is the study of a trait through several generations of a family, drawn as a family tree with standard symbols. It shows whether a trait is dominant or recessive and whether it is autosomal or sex-linked, identifies likely carriers, and helps predict the chance of the trait in future children.
What is a point mutation? Give one example.Answer: A mutation caused by a change in a single base pair of DNA. Example: sickle-cell anaemia, where GAG changes to GUG at the sixth codon of the beta-globin gene, so valine replaces glutamic acid.
Mention any two autosomal genetic disorders with their symptoms.Answer: Sickle-cell anaemia: red blood cells become sickle-shaped under low oxygen tension, causing anaemia. Phenylketonuria: phenylalanine and phenylpyruvic acid accumulate, causing mental retardation, and are excreted in urine. (Thalassemia, with anaemia from too few globin chains, is another.)

Common Mistakes to Avoid

Watch out

Calling sickle-cell anaemia sex-linked. Correct: it is autosome-linked recessive; haemophilia and colour blindness are X-linked.
Saying Hb^A Hb^S individuals have the disease. Correct: they are carriers with the sickle-cell trait; only Hb^S Hb^S is diseased.
Writing GAG → GTG for the mRNA. Correct: the mRNA changes from GAG to GUG; GTG is the DNA coding strand.
Placing $β$ thalassemia on chromosome 16. Correct: $β$ (HBB) is on chromosome 11; $α$ (HBA1, HBA2) is on chromosome 16.
Saying Down's syndrome is a monosomy. Correct: it is trisomy 21, with 47 chromosomes.
Giving Turner's syndrome 47 chromosomes. Correct: Turner's is 45, X0; Klinefelter's is 47, XXY.
Saying aneuploidy comes from failed cytokinesis. Correct: aneuploidy comes from failed segregation of chromatids; polyploidy from failed cytokinesis.
Saying a carrier mother is colour blind. Correct: her normal dominant gene masks the recessive one.

Frequently Asked Questions

What is the difference between a point mutation and a frame-shift mutation?

A point mutation is a change in a single base pair of DNA, as in sickle-cell anaemia. A frame-shift mutation is caused by the deletion or insertion of base pairs, which shifts the way the following bases are read.

Why is colour blindness much more common in males than in females?

The genes for red-green colour blindness lie on the X chromosome and are recessive. A male has only one X, so one mutant gene makes him colour blind. A female needs the mutant gene on both X chromosomes. So it affects about 8 per cent of males but only 0.4 per cent of females.

How is haemophilia inherited?

Haemophilia is a sex-linked recessive disease. An unaffected carrier female passes the mutant X to some of her sons, who then suffer non-stop bleeding from a simple cut because a clotting-cascade protein is affected. A haemophilic female is extremely rare. Queen Victoria was a carrier.

What is the molecular basis of sickle-cell anaemia?

A single base substitution at the sixth codon of the beta-globin gene changes GAG to GUG, so valine replaces glutamic acid at the sixth position of the beta chain. The mutant haemoglobin polymerises under low oxygen tension, and the red blood cells change from biconcave discs to sickle shapes.

How does thalassemia differ from sickle-cell anaemia?

Thalassemia is a quantitative problem: too few globin chains are made, because of mutation or deletion. Sickle-cell anaemia is a qualitative problem: a globin that functions incorrectly is made. Both are autosomal recessive blood disorders that cause anaemia.

What is the difference between aneuploidy and polyploidy?

Aneuploidy is the gain or loss of one or a few chromosomes, caused by the failure of chromatids to segregate during cell division, as in Down's and Turner's syndromes. Polyploidy is an increase in a whole set of chromosomes, caused by the failure of cytokinesis after telophase, and is often seen in plants.

What are the features of Down's syndrome?

Down's syndrome is caused by trisomy of chromosome 21. The individual is short statured, with a small round head, a furrowed tongue and a partially open mouth. The palm is broad with a characteristic palm crease, and physical, psychomotor and mental development is retarded. Langdon Down described it in 1866.

How do Klinefelter's and Turner's syndromes differ?

Klinefelter's syndrome is caused by an extra X chromosome (47, XXY): the individual is male, with feminine features such as gynaecomastia, and sterile. Turner's syndrome is caused by a missing X (45, X0): the individual is a sterile female with rudimentary ovaries and lacks other secondary sexual characters.

Previous year questions on Genetic Mutation and Disorders

4 questions from past papers, each with a step-by-step solution.

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