Chromosomal Theory and Genetic Disorders

How chromosomes carry the genes Mendel described, and what happens when things go wrong.

Chromosomal Theory of Inheritance

The Chromosomal Theory of Inheritance explains that genes are located on chromosomes and that the behaviour of chromosomes during meiosis provides the physical basis for Mendel's laws of inheritance.

In simple words, genes are the units of heredity and chromosomes carry these genes. Meiosis में chromosomes का separation और independent assortment ही उन genetic factors के inheritance का physical basis प्रदान करता है जिनकी कल्पना Mendel ने की थी।

Development of the Chromosomal Theory

In 1902, Walter Sutton and Theodor Boveri independently proposed the Chromosomal Theory of Inheritance.

Scientist Contribution
Walter Sutton Proposed that Mendelian factors are located on chromosomes.
Theodor Boveri Provided evidence supporting the role of chromosomes in heredity.

Basis of the Chromosomal Theory

  • Chromosomes occur in pairs in diploid organisms.
  • Genes are located on chromosomes.
  • Homologous chromosomes separate during meiosis.
  • Alleles of a gene are present at corresponding positions on homologous chromosomes.
  • Different chromosome pairs can assort independently during meiosis.
  • Fertilisation restores the diploid chromosome number.
Important: Mendel described inheritance in terms of factors or genes, while Sutton and Boveri connected these factors with chromosomes. Thus, chromosomes provide the physical basis of Mendelian inheritance.

Chromosomes and Mendel's Laws

Mendel's Concept Chromosomal Basis
Law of Dominance Interaction between alleles present on homologous chromosomes.
Law of Segregation Homologous chromosomes separate during meiosis, causing separation of alleles into different gametes.
Law of Independent Assortment Different homologous chromosome pairs can assort independently during meiosis, provided the genes are not linked.

Sex Determination

Sex determination is the mechanism by which the sex of an individual is established. Different organisms use different mechanisms for determining sex.

Sex Determination in Humans

Humans have 23 pairs of chromosomes. Out of these, 22 pairs are autosomes and one pair consists of sex chromosomes.

Individual Chromosome Constitution Gametes
Female 44 + XX All ova carry X chromosome
Male 44 + XY 50% X-bearing sperm and 50% Y-bearing sperm

The female produces only one type of ovum with respect to sex chromosome: X.

The male produces two types of sperm: X-bearing sperm and Y-bearing sperm.

X sperm Y sperm
X ovum XX (Female) XY (Male)

Therefore, the sex of the child is determined by the type of sperm that fertilises the ovum. Thus, biologically, the father determines the sex of the child.

Exam Point: The probability of a male or female child is approximately 50% each. The sex of a child is not determined by the mother.

Other Mechanisms of Sex Determination

Sex determination is not identical in all organisms.

Mechanism Example
XX-XY type Humans, mammals
XX-XO type Grasshoppers
ZZ-ZW type Birds

In birds, the female is heterogametic (ZW), whereas the male is homogametic (ZZ).

Mutation

A mutation is a sudden and heritable change in the genetic material of an organism.

Mutations may occur in a gene or at the chromosome level. Some mutations may produce genetic disorders or variations.

Types of Mutations

Type Meaning
Gene mutation Change in the nucleotide sequence of a gene.
Chromosomal mutation Change in chromosome structure or chromosome number.

Genetic Disorders

Genetic disorders are diseases or abnormalities caused by changes in genes or chromosomes.

They may be broadly classified into:

  1. Mendelian disorders
  2. Chromosomal disorders

Mendelian Disorders

Mendelian disorders are caused by alterations or mutations in a single gene and are generally inherited according to Mendelian principles.

Important Mendelian Disorders

Disorder Cause / Inheritance Important Feature
Haemophilia X-linked recessive Impaired blood clotting
Thalassemia Autosomal recessive Reduced synthesis of globin chains
Sickle-cell anaemia Autosomal recessive Abnormal haemoglobin and sickle-shaped RBCs
Phenylketonuria Autosomal recessive Inability to properly metabolise phenylalanine

Haemophilia

Haemophilia is an X-linked recessive disorder in which the blood fails to clot normally.

The condition occurs due to deficiency or absence of certain clotting factors. Even a small injury may cause prolonged bleeding.

Because the gene is located on the X chromosome, males are more commonly affected. A male has only one X chromosome, so a recessive allele on that chromosome can express the disorder.

Key Point: Haemophilia is an example of an X-linked recessive disorder.

Sickle-cell Anaemia

Sickle-cell anaemia is an autosomal recessive genetic disorder caused by a mutation in the gene coding for the beta chain of haemoglobin.

A single base substitution in the gene causes the amino acid glutamic acid to be replaced by valine at the sixth position of the beta-globin chain.

As a result, abnormal haemoglobin called HbS is formed.

Under low oxygen conditions, RBCs containing HbS become elongated and sickle-shaped. यह abnormal shape blood circulation में बाधा डाल सकती है और anaemia तथा अन्य complications उत्पन्न कर सकती है।

Normal Sickle-cell condition
Normal haemoglobin (HbA) Abnormal haemoglobin (HbS)
Normal-shaped RBCs Sickle-shaped RBCs under low O2
Normal β-globin sequence Glutamic acid replaced by valine at 6th position

Inheritance of Sickle-cell Anaemia

Let HbA represent the normal allele and HbS represent the sickle-cell allele.

Genotype Condition
HbAHbA Normal
HbAHbS Carrier / heterozygous
HbSHbS Sickle-cell anaemia

Thalassemia

Thalassemia is an inherited blood disorder caused by reduced synthesis of one or more globin chains of haemoglobin.

Depending on the affected globin chain, it may be classified as alpha-thalassemia or beta-thalassemia.

Thalassemia is an autosomal recessive disorder. इसलिए disease phenotype सामान्यतः तब दिखाई देता है जब व्यक्ति को defective alleles दोनों parents से प्राप्त हों।

Phenylketonuria

Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficiency of the enzyme required for the metabolism of the amino acid phenylalanine.

Phenylalanine accumulates in the body and may lead to severe intellectual disability if untreated.

PKU is inherited as an autosomal recessive disorder.

Chromosomal Disorders

Chromosomal disorders are caused by abnormalities in chromosome number or chromosome structure.

Changes in chromosome number may occur because of failure of chromosomes to separate properly during cell division. This phenomenon is called non-disjunction.

Non-disjunction

Non-disjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division.

इससे gametes में chromosome number सामान्य से अधिक या कम हो सकता है। Fertilisation के बाद ऐसी abnormal chromosome number वाली condition aneuploidy पैदा कर सकती है।

Term Meaning
Euploidy Change involving complete sets of chromosomes.
Aneuploidy Gain or loss of one or a few chromosomes.
Trisomy Presence of an extra chromosome: 2n + 1.
Monosomy Loss of one chromosome: 2n − 1.

Down's Syndrome

Down's syndrome is a chromosomal disorder caused by the presence of an additional copy of chromosome 21.

It is therefore known as trisomy of chromosome 21.

The chromosome constitution is generally represented as 47 chromosomes instead of the normal 46.

Feature Down's Syndrome
Chromosome involved Chromosome 21
Condition Trisomy 21
Chromosome number 47
Cause Non-disjunction

Klinefelter's Syndrome

Klinefelter's syndrome occurs in males due to the presence of an extra X chromosome.

The chromosome constitution is 47, XXY.

Feature Klinefelter's Syndrome
Sex Male
Chromosome constitution 47, XXY
Cause Non-disjunction
Common feature Sterile male with some female characteristics

Turner's Syndrome

Turner's syndrome occurs in females due to the absence of one X chromosome.

The chromosome constitution is 45, XO.

Feature Turner's Syndrome
Sex Female
Chromosome constitution 45, XO
Cause Loss of one X chromosome
Common feature Sterile female with underdeveloped ovaries

Major Genetic Disorders at a Glance

Disorder Type Main Cause
Haemophilia Mendelian X-linked recessive gene
Sickle-cell anaemia Mendelian Mutation in β-globin gene
Thalassemia Mendelian Reduced globin-chain synthesis
Phenylketonuria Mendelian Defect in phenylalanine metabolism
Down's syndrome Chromosomal Trisomy 21
Klinefelter's syndrome Chromosomal 47, XXY
Turner's syndrome Chromosomal 45, XO

Important Terminology

Term Meaning
Autosome Chromosome other than a sex chromosome
Sex chromosome Chromosome involved in sex determination
Heterogametic Individual producing two types of sex-chromosome-bearing gametes
Homogametic Individual producing only one type of sex-chromosome-bearing gamete
Mutation Sudden heritable change in genetic material
Non-disjunction Failure of chromosomes to separate properly
Trisomy 2n + 1 chromosome condition
Monosomy 2n − 1 chromosome condition

Board Important Questions

Very Short Answer Questions

  1. Who proposed the Chromosomal Theory of Inheritance?
  2. How many pairs of chromosomes are present in humans?
  3. What is non-disjunction?
  4. What is trisomy?
  5. Which chromosome is present in trisomy 21?
  6. What is the chromosome constitution of Klinefelter's syndrome?
  7. What is the chromosome constitution of Turner's syndrome?
  8. Which sex is heterogametic in humans?
  9. Name one X-linked genetic disorder.
  10. Name one autosomal recessive disorder.

Short Answer Questions

  1. Explain the Chromosomal Theory of Inheritance.
  2. How does meiosis provide the chromosomal basis of Mendel's Law of Segregation?
  3. Explain sex determination in humans.
  4. What is non-disjunction? How can it cause genetic disorders?
  5. Write a short note on haemophilia.
  6. Explain the genetic basis of sickle-cell anaemia.
  7. Differentiate between Down's syndrome and Turner's syndrome.
  8. What is Klinefelter's syndrome?

Long Answer Questions

  1. Describe the Chromosomal Theory of Inheritance and explain its relationship with Mendel's laws.
  2. Explain sex determination in humans with a suitable cross.
  3. Describe important Mendelian and chromosomal genetic disorders.
  4. Explain sickle-cell anaemia with reference to its molecular basis and inheritance.

Multiple Choice Questions

  1. The Chromosomal Theory of Inheritance was proposed by:
    (A) Darwin and Wallace
    (B) Sutton and Boveri
    (C) Watson and Crick
    (D) Meselson and Stahl
    Answer: (B) Sutton and Boveri
  2. The heterogametic sex in humans is:
    (A) Female
    (B) Male
    (C) Both
    (D) Neither
    Answer: (B) Male
  3. Down's syndrome is caused by:
    (A) Monosomy X
    (B) Trisomy 21
    (C) XXY
    (D) Deletion of Y chromosome
    Answer: (B) Trisomy 21
  4. Klinefelter's syndrome has the chromosome constitution:
    (A) 45, XO
    (B) 46, XY
    (C) 47, XXY
    (D) 47, XYY
    Answer: (C) 47, XXY
  5. Turner's syndrome is represented by:
    (A) XXY
    (B) XO
    (C) XXX
    (D) XYY
    Answer: (B) XO
  6. Haemophilia is generally:
    (A) Autosomal dominant
    (B) Autosomal recessive
    (C) X-linked recessive
    (D) Y-linked
    Answer: (C) X-linked recessive
  7. Sickle-cell anaemia is caused by a mutation in the gene coding for:
    (A) Alpha-globin
    (B) Beta-globin
    (C) Insulin
    (D) Collagen
    Answer: (B) Beta-globin
  8. In sickle-cell anaemia, glutamic acid is replaced by:
    (A) Glycine
    (B) Alanine
    (C) Valine
    (D) Lysine
    Answer: (C) Valine
  9. Failure of chromosomes to separate properly is called:
    (A) Crossing over
    (B) Mutation
    (C) Non-disjunction
    (D) Synapsis
    Answer: (C) Non-disjunction
  10. Thalassemia is mainly associated with defective synthesis of:
    (A) Globin chains
    (B) Lipids
    (C) DNA polymerase
    (D) Insulin
    Answer: (A) Globin chains
  11. A chromosome number of 2n + 1 represents:
    (A) Monosomy
    (B) Trisomy
    (C) Haploidy
    (D) Polyploidy
    Answer: (B) Trisomy
  12. A chromosome number of 2n − 1 represents:
    (A) Trisomy
    (B) Monosomy
    (C) Triploidy
    (D) Tetraploidy
    Answer: (B) Monosomy
  13. In humans, ova normally carry:
    (A) X chromosome only
    (B) Y chromosome only
    (C) Either X or Y
    (D) No sex chromosome
    Answer: (A) X chromosome only
  14. The chromosome constitution of a normal human male is:
    (A) 44 + XX
    (B) 44 + XY
    (C) 22 + XY
    (D) 46 + XY
    Answer: (B) 44 + XY
  15. Phenylketonuria is associated with defective metabolism of:
    (A) Tyrosine
    (B) Phenylalanine
    (C) Glycine
    (D) Tryptophan
    Answer: (B) Phenylalanine

Fill in the Blanks

  1. The Chromosomal Theory of Inheritance was proposed by ______ and ______.
  2. Humans have ______ pairs of chromosomes.
  3. The male is the ______ sex in humans.
  4. Down's syndrome is caused by ______ of chromosome 21.
  5. Klinefelter's syndrome has the chromosome constitution ______.
  6. Turner's syndrome has the chromosome constitution ______.
  7. Failure of chromosome separation is called ______.
  8. Haemophilia is an ______-linked recessive disorder.
  9. Sickle-cell anaemia involves abnormal ______.
  10. Thalassemia affects the synthesis of ______ chains.

Match the Following

Column A Column B
1. Down's syndrome a. 45, XO
2. Klinefelter's syndrome b. X-linked recessive
3. Turner's syndrome c. Trisomy 21
4. Haemophilia d. 47, XXY

Answers: 1-c, 2-d, 3-a, 4-b

Quick Revision

  • Sutton + Boveri → Chromosomal Theory of Inheritance
  • Human female → 44 + XX
  • Human male → 44 + XY
  • Male → Heterogametic sex
  • Haemophilia → X-linked recessive
  • Sickle-cell anaemia → β-globin gene mutation
  • Glutamic acid → Valine → Sickle-cell anaemia
  • Thalassemia → Reduced globin-chain synthesis
  • Down's syndrome → Trisomy 21 → 47 chromosomes
  • Klinefelter's syndrome → 47, XXY → Male
  • Turner's syndrome → 45, XO → Female
  • Non-disjunction → Failure of chromosome separation
  • Trisomy → 2n + 1
  • Monosomy → 2n − 1

Genes are carried on chromosomes, and chromosome behaviour during meiosis provides the physical basis of inheritance.

Lesson 7 of 24
On This Page