Principles of Inheritance and Variation - Notes | Class 12

Genetic Disorders

1. Mendelian Disorders

It is caused by alteration or mutation in a single gene.
E.g., Haemophilia, Colour Blindness, Sickle-Cell Anaemia, Phenylketonuria, Thalassemia, Cystic Fibrosis, etc.
The pattern of inheritance of Mendelian disorders can be traced in a family by pedigree analysis.
Mendelian disorders may be dominant or recessive.
Pedigree analysis helps to understand whether the trait is dominant or recessive.

Pedigree analysis of (A) Autosomal dominant trait (E.g., Myotonic dystrophy) and (B) Autosomal recessive trait (E.g., Sickle-cell anaemia)

It is a sex-linked (X-linked) recessive disease.
In this, a protein involved in blood clotting is affected.
A simple cut results in non-stop bleeding.
The disease is controlled by 2 alleles, H & h.
H is the normal allele, and h is responsible for haemophilia.
Genotypes and phenotypes:
- X^HX^H: Normal female
- X^HX^h: Heterozygous female (carrier). She may transmit the disease to sons.
- X^hX^h: Haemophilic female
- X^HY: Normal male
- X^hY: Haemophilic male
In females, haemophilia is very rare because it happens only when the mother is at least a carrier and the father is haemophilic (unviable in the later stage of life).
Queen Victoria was a carrier of haemophilia. So her family pedigree shows many haemophilic descendants.

It is a sex-linked (X-linked) recessive disorder due to a defect in either the red or green cone of the eye.
It results in failure to discriminate between red and green colour.
It is due to a mutation in some genes in the X chromosome.
It occurs in 8% of males and only about 0.4% of females. This is because the genes are X-linked.
The normal allele is dominant (C). The recessive allele (c) causes colour blindness.
The son of a heterozygous woman (carrier, X^CX^c) has a 50% chance of being colour blind.
A daughter will be colour blind only when her mother is at least a carrier and her father is colour blind (X^cY).

This is an autosome-linked recessive disease.
It can be transmitted from parents to the offspring when both the partners are carriers (heterozygous) for the gene.
The disease is controlled by a pair of alleles, Hb^A and Hb^S.
Genotypes and phenotypes:
- Homozygous dominant (Hb^AHb^A): Normal
- Heterozygous (Hb^AHb^S): Carrier; sickle-cell trait
- Homozygous recessive (Hb^SHb^S): Affected
The defect is caused by the substitution of Glutamic acid (Glu) by Valine (Val) at the sixth position of the β-globin chain of haemoglobin (Hb).

This is due to the single base substitution at the sixth codon of the β-globin gene from GAG to GUG.
The mutant Hb molecule undergoes polymerization under low oxygen tension, causing the change in the shape of the RBC from a biconcave disc to an elongated sickle-like structure.
Sickle-cell anaemia is a qualitative problem (synthesizes incorrectly functioning globin).

An inborn error of metabolism.
An autosomal recessive disease.
It is due to a mutation of a gene that codes for the enzyme phenylalanine hydroxylase. This enzyme converts the amino acid phenylalanine into tyrosine.
The affected individual lacks this enzyme. As a result, phenylalanine accumulates and converts into phenyl pyruvic acid and other derivatives.
They accumulate in the brain, resulting in mental retardation. These are also excreted through urine because of poor absorption by the kidney.

An autosome-linked recessive blood disease.
It is transmitted from unaffected carrier (heterozygous) parents to offspring.
It is due to mutation or deletion.
It results in reduced synthesis of α or β globin chains of haemoglobin. It forms abnormal haemoglobin and causes anaemia.
Based on the chain affected, thalassemia is of 2 types:
- α Thalassemia: Here, production of the α globin chain is affected. It is controlled by two closely linked genes HBA1 & HBA2 on chromosome 16 of each parent. Mutation or deletion of one or more of the four genes causes the disease. The more genes affected, the fewer α globin molecules produced.
- β Thalassemia: Here, production of the β globin chain is affected. It is controlled by a single gene HBB on chromosome 11 of each parent. Mutation of one or both genes causes the disease.
Thalassemia is a quantitative problem (synthesizes very few globin molecules).

They are caused due to the absence, excess, or abnormal arrangement of one or more chromosomes.
2 types:
- Aneuploidy: The gain or loss of chromosomes due to the failure of segregation of chromatids during cell division.
- Polyploidy (Euploidy): It is an increase in a whole set of chromosomes due to the failure of cytokinesis after the telophase stage of cell division. This is very rare in humans but often seen in plants.

It is the presence of an additional copy of chromosome number 21 (trisomy of 21).
Genetic constitution: 45 A + XX or 45 A + XY (i.e., 47 chromosomes).
Features:
- They are short-statured with a small round head.
- Broad flat face.
- Furrowed big tongue and partially open mouth.
- Many “loops” on fingertips.
- Broad palm with a characteristic palm simian crease.
- Retarded physical, psychomotor, and mental development.
- Congenital heart disease.

It is the presence of an additional copy of the X-chromosome in males (trisomy).
Genetic constitution: 44 A + XXY (i.e., 47 chromosomes).
Features:
- Overall masculine development. However, feminine development is also expressed, e.g., development of breasts (Gynaecomastia).
- Sterile.
- Mentally retarded.

This is the absence of one X chromosome in females (monosomy).
Genetic constitution: 44 A + X0 (i.e., 45 chromosomes).
Features:
- Sterile, ovaries are rudimentary.
- Lack of other secondary sexual characteristics.
- Dwarf.
- Mentally retarded.