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Principles of Inheritance and Variation - Mendelian Disorders

Grade 12CBSEBiology

Review the key concepts, formulae, and examples before starting your quiz.

🔑Concepts

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Mendelian disorders are primarily determined by alteration or mutation in a single gene, following the laws of inheritance described by Mendel.

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Haemophilia: An X-linked recessive disorder where a single protein involved in the clotting of blood is affected. A heterozygous female (carrier) XhXX^hX may transmit the disease to sons.

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Sickle-cell Anemia: An autosomal recessive disorder caused by the substitution of Glutamic acid (GluGlu) by Valine (ValVal) at the sixth position of the β\beta-globin chain of hemoglobin.

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The mutant hemoglobin molecule undergoes polymerization under low oxygen tension causing the change in the shape of the RBC from biconcave disc to elongated sickle-like structure.

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Phenylketonuria (PKU): An inborn error of metabolism (autosomal recessive). Affected individuals lack the enzyme phenylalanine hydroxylase that converts the amino acid phenylalanine into tyrosine.

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Thalassemia: An autosomal linked recessive blood disease characterized by the reduced rate of synthesis of one of the globin chains (α\alpha or β\beta). It is a quantitative problem (too few globin molecules produced), unlike Sickle-cell anemia which is qualitative.

📐Formulae

HbAHbS×HbAHbS→1HbAHbA:2HbAHbS:1HbSHbSHb^A Hb^S \times Hb^A Hb^S \rightarrow 1 Hb^A Hb^A : 2 Hb^A Hb^S : 1 Hb^S Hb^S

Mutation in Sickle Cell: GAG(Glu)→MutationGUG(Val)\text{Mutation in Sickle Cell: } GAG (Glu) \xrightarrow{\text{Mutation}} GUG (Val)

α-Thalassemia genes located on Chromosome 16:HBA1,HBA2\alpha\text{-Thalassemia genes located on Chromosome } 16: HBA1, HBA2

β-Thalassemia gene located on Chromosome 11:HBB\beta\text{-Thalassemia gene located on Chromosome } 11: HBB

25% (Normal)50% (Carrier)+25% (Affected)100% (Total inheritance probability)\begin{array}{r} 25\% \text{ (Normal)} \\ 50\% \text{ (Carrier)} \\ + 25\% \text{ (Affected)} \\ \hline 100\% \text{ (Total inheritance probability)} \end{array}

💡Examples

Problem 1:

A carrier woman for Haemophilia (XhXX^hX) marries a normal man (XYXY). What is the probability of their son being affected?

Solution:

The cross results in: XhXX^hX (Carrier Daughter), XXXX (Normal Daughter), XhYX^hY (Affected Son), and XYXY (Normal Son). The ratio of sons is 11 affected : 11 normal.

Explanation:

Since the question asks for the probability among sons, 50%50\% of the male offspring will be affected (XhYX^hY).

Problem 2:

If both parents are carriers for Sickle-cell anemia (HbAHbSHb^A Hb^S), what percentage of the offspring will show the diseased phenotype?

Solution:

Genotypic distribution: 1/4HbAHbA1/4 Hb^A Hb^A (Normal), 1/2HbAHbS1/2 Hb^A Hb^S (Carrier), 1/4HbSHbS1/4 Hb^S Hb^S (Affected).

Explanation:

Only the homozygous recessive individual (HbSHbSHb^S Hb^S) shows the phenotype. Therefore, the percentage is 25%25\%.

Problem 3:

In Thalassemia, if a child inherits defective genes for α\alpha-globin from both parents, how many total genes might be affected on Chromosome 1616?

Solution:

Up to 44 alleles.

Explanation:

α\alpha-Thalassemia is controlled by two closely linked genes HBA1HBA1 and HBA2HBA2 on each chromosome 1616. With two chromosomes, there are 44 alleles in total (2×22 \times 2). The more genes affected, the less α\alpha-globin is produced.