Which one of the following genetic diseases is sex-linked ?

1. Basics of Human Genetics: Chromosomes and Karyotypes (basic)

At the heart of every living cell lies a 'blueprint' that dictates our physical form and functions. This blueprint is written in DNA (Deoxyribonucleic Acid), which is organized into thread-like structures called chromosomes located within the cell nucleus Science, Class X (NCERT 2025 ed.), How do Organisms Reproduce?, p.113. In humans, every normal body cell contains 46 chromosomes, arranged in 23 pairs. We inherit one set of 23 from our mother and another set of 23 from our father. This 'doubling up' ensures we have two copies of every gene, but it also creates a biological challenge: if we passed on all 46, the next generation would have 92! To prevent this, specialized reproductive cells (sperm and egg) undergo a process to carry only half the number of chromosomes (23 total), ensuring the count remains stable across generations Science, Class X (NCERT 2025 ed.), How do Organisms Reproduce?, p.120. Of these 23 pairs, 22 are known as autosomes. These pairs are 'perfect' matches, meaning the maternal and paternal copies carry the same types of genes in the same order. However, the 23rd pair — the sex chromosomes — is the exception. This pair determines the biological sex of the individual. In females, this pair is a perfect match of two large chromosomes called XX. In males, however, it is a mismatched pair consisting of one normal-sized X and one significantly shorter Y chromosome Science, Class X (NCERT 2025 ed.), Heredity, p.132. When we look at a complete set of these chromosomes under a microscope, organized by size and shape, we call it a karyotype. Because women always pass an X chromosome to their children, it is the paternal contribution (the father's sperm) that decides the child's sex. If the sperm carries an X, the child is a girl (XX); if it carries a Y, the child is a boy (XY) Science, Class X (NCERT 2025 ed.), Heredity, p.133.

Feature	Autosomes	Sex Chromosomes
Quantity	22 Pairs (1–22)	1 Pair (23rd)
Function	Determine general body traits	Determine biological sex
Pairing	Always identical in shape/size	XX (Female) or XY (Male)

Sources: Science, Class X (NCERT 2025 ed.), Heredity, p.132-133; Science, Class X (NCERT 2025 ed.), How do Organisms Reproduce?, p.113, 120

2. Mendelian Inheritance: Dominant vs. Recessive Alleles (basic)

In the study of genetics, we begin with the fundamental rule that every sexually reproducing organism receives a set of instructions from both parents. This means that for every physical trait — whether it is the height of a pea plant or the color of a human eye — there are two versions of the gene responsible for it, one from the mother and one from the father Science, class X (NCERT 2025 ed.), Heredity, p.129. These different versions of the same gene are called alleles.

Gregor Mendel, often called the father of genetics, discovered that these two alleles do not always have equal power. Through his experiments with garden peas, he observed that some traits could effectively "mask" others. He coined the term Dominant trait for the version that expresses itself even if only one copy is present (e.g., 'T' for tallness). Conversely, a Recessive trait is one that remains hidden or suppressed unless the individual inherits two identical copies of that version (e.g., 't' for shortness) Science, class X (NCERT 2025 ed.), Heredity, p.130. This is why a plant with the genetic makeup Tt looks just as tall as a plant with TT; the single 'T' is enough to determine the physical outcome.

To understand the logic behind inheritance, it is helpful to distinguish between what an organism is genetically and what it looks like physically. We call the genetic toolkit (the actual alleles like TT, Tt, or tt) the Genotype, while the observable physical characteristic (Tall or Short) is the Phenotype. In a population, recessive traits can "hide" in the genotype for generations, only appearing in the phenotype when two carriers of the recessive allele produce an offspring that inherits the recessive version from both parents Science, class X (NCERT 2025 ed.), Heredity, p.133.

Feature	Dominant Allele	Recessive Allele
Expression	Expressed even if only one copy is present (Heterozygous or Homozygous).	Expressed only if two copies are present (Homozygous).
Notation	Represented by an Upper-case letter (e.g., T).	Represented by a lower-case letter (e.g., t).
Example	Tallness in pea plants, Round seeds.	Shortness in pea plants, Wrinkled seeds.

Sources: Science, class X (NCERT 2025 ed.), Heredity, p.129; Science, class X (NCERT 2025 ed.), Heredity, p.130; Science, class X (NCERT 2025 ed.), Heredity, p.133

3. Broad Classification of Genetic Disorders (intermediate)

To understand genetic disorders, we must first look at how our genetic 'instruction manual' is organized. In humans, DNA is not one long continuous string; it is divided into separate, independent pieces called chromosomes. Every cell contains two copies of each chromosome—one from the father and one from the mother Science, class X (NCERT 2025 ed.), Heredity, p.132. Genetic disorders arise when there is a 'typo' or a structural error in this manual. We broadly classify these into two major categories: Mendelian Disorders and Chromosomal Disorders.

Mendelian Disorders are caused by an alteration or mutation in a single gene. These follow the classic patterns of inheritance that Gregor Mendel discovered, such as being dominant or recessive Science, class X (NCERT 2025 ed.), Heredity, p.133. These are further sub-classified based on which chromosome the 'typo' is located on:

• Autosomal Disorders: The mutation occurs on any of the 22 pairs of non-sex chromosomes. Examples include Cystic Fibrosis and Sickle Cell Anemia.
• Sex-linked Disorders: The mutation occurs on the sex chromosomes (X or Y). Since women are XX and men are XY, these disorders often affect the sexes differently Science, class X (NCERT 2025 ed.), Heredity, p.132. Haemophilia is a classic X-linked recessive example.

Chromosomal Disorders, on the other hand, are not about a single gene mutation but involve the entire chromosome. These occur when there is an abnormal number (aneuploidy) or a structural change in the chromosomes. For instance, having an extra copy of Chromosome 21 leads to Down’s Syndrome. Unlike Mendelian disorders, these are usually not 'inherited' from parents but occur due to errors during the formation of germ cells (sperm or egg).

Feature	Mendelian Disorders	Chromosomal Disorders
Root Cause	Mutation in a single gene.	Absence, excess, or abnormal arrangement of chromosomes.
Inheritance	Follows predictable Mendelian patterns (Dominant/Recessive).	Usually sporadic; not necessarily inherited from parents.
Examples	Haemophilia, Thalassemia, Color blindness.	Down's Syndrome, Turner's Syndrome.

Sources: Science, class X (NCERT 2025 ed.), Heredity, p.132; Science, class X (NCERT 2025 ed.), Heredity, p.133

4. Autosomal Recessive Disorders: Cystic Fibrosis and Tay-Sachs (intermediate)

To understand disorders like Cystic Fibrosis and Tay-Sachs, we must first look at the fundamental rules of inheritance. In human genetics, for most traits, we receive one version of a gene (an allele) from each parent Science, Class X (NCERT 2025 ed.), Heredity, p.129. An autosomal recessive disorder occurs only when a child inherits two 'faulty' or mutated versions of a gene—one from each parent. Because these genes are located on autosomes (the 22 pairs of non-sex chromosomes), these disorders affect males and females with equal frequency and probability.

If an individual carries only one mutated allele and one normal allele, they are known as a carrier. Carriers are typically healthy and show no symptoms because their single 'dominant' normal allele produces enough functional protein to mask the 'recessive' mutated one Science, Class X (NCERT 2025 ed.), Heredity, p.130. However, when two carriers have a child, there is a 25% chance (1 in 4) that the child will inherit the mutated allele from both parents, manifesting the condition.

Disorder	Biological Impact	Primary Symptoms
Cystic Fibrosis (CF)	Mutation in the CFTR gene affecting salt/water transport across membranes.	Build-up of thick, sticky mucus in lungs and pancreas; chronic respiratory infections.
Tay-Sachs Disease	Absence of the enzyme Hexosaminidase A (Hex-A), which breaks down fatty acids.	Accumulation of lipids in the brain, leading to progressive neurological decline and loss of motor skills.

Sources: Science, Class X (NCERT 2025 ed.), Heredity, p.129; Science, Class X (NCERT 2025 ed.), Heredity, p.130

5. Multifactorial Conditions: The Case of Hypertension (intermediate)

In our study of genetics, we often start with Mendelian inheritance, where a single gene determines a specific trait. however, many human health conditions, such as Hypertension (High Blood Pressure), do not follow this simple 'one-gene-one-trait' rule. Instead, they are multifactorial. This means the condition arises from the complex interplay of polygenic factors (multiple genes acting together) and environmental influences. While every individual inherits a set of genetic blueprints from both parents Science, Class X, Heredity, p.129, these genes only set a range of possibilities or a 'predisposition.'

Hypertension is a classic example of a non-communicable disease (NCD). Unlike diseases caused by pathogens that spread from person to person, NCDs are usually linked to how we live Science, Class VIII, Health: The Ultimate Treasure, p.32. For instance, even if a person has a genetic tendency toward high blood pressure, their lifestyle choices—such as salt intake, levels of physical activity, and consumption of processed foods—play a critical role in whether the disease actually manifests Science, Class VIII, Health: The Ultimate Treasure, p.33. This is why medical professionals focus heavily on lifestyle changes as a primary method of management Science, Class VIII, Health: The Ultimate Treasure, p.36.

Understanding the distinction between single-gene disorders and multifactorial conditions is vital. In single-gene disorders, the presence of a specific allele often guarantees the phenotype. In multifactorial conditions like hypertension, variations arise during reproduction Science, Class X, Heredity, p.133 that may make an individual more sensitive to environmental triggers, but the environment determines the final outcome.

Feature	Monogenic Traits	Multifactorial Traits (e.g., Hypertension)
Genetic Basis	Single gene pair	Multiple genes (Polygenic)
Environment	Minimal impact on expression	Significant role in triggering the condition
Inheritance Pattern	Follows clear Mendelian ratios	Complex; shows familial clustering but no simple ratio

Sources: Science, Class VIII, Health: The Ultimate Treasure, p.32; Science, Class VIII, Health: The Ultimate Treasure, p.33; Science, Class VIII, Health: The Ultimate Treasure, p.36; Science, Class X, Heredity, p.129; Science, Class X, Heredity, p.133

6. Sex-linked Inheritance: X-linked Recessive Traits (exam-level)

To understand X-linked recessive inheritance, we must first look at how sex is determined. In humans, sex is determined by a specific pair of chromosomes: females have two X chromosomes (XX), while males have one X and one Y chromosome (XY) Science, Class X, Heredity, p.133. Because the X chromosome is much larger than the Y, it carries many essential genes that have no counterpart on the Y chromosome. When a trait is 'X-linked recessive,' it means the gene responsible for the trait is located on the X chromosome and behaves recessively. In genetics, a recessive trait is one that only expresses itself when both copies of the gene are identical (homozygous), or if there is no dominant version of the gene present to mask it Science, Class X, Heredity, p.130. This creates a unique disparity between the sexes. Since females have two X chromosomes, they usually have a 'backup' healthy gene if one X carries a mutation. Such females are called carriers; they do not show the disease but can pass it to their children. Males, however, are hemizygous—they have only one X chromosome. If that single X carries the recessive mutation, there is no second X to provide a dominant, healthy allele, so the trait is expressed fully.

Compare the inheritance patterns between the sexes below:

Feature	Males (XY)	Females (XX)
Allele Requirement	Only one copy needed to show the trait.	Two copies needed to show the trait.
Carrier Status	Cannot be carriers; they are either affected or normal.	Can be carriers (heterozygous) without showing symptoms.
Inheritance Source	Always inherits the X from the mother.	Inherits one X from each parent.

Classic examples of this pattern include Royal Haemophilia (a blood-clotting disorder) and Red-Green Color Blindness. These differ from autosomal disorders, such as cystic fibrosis or Tay-Sachs, which are located on non-sex chromosomes and affect both males and females with equal frequency. In the case of X-linked traits, you will often see a 'criss-cross' inheritance pattern where an affected grandfather passes the trait to his grandson through a carrier daughter.

Sources: Science, Class X, Heredity, p.133; Science, Class X, Heredity, p.130

7. Solving the Original PYQ (exam-level)

Now that you have mastered the difference between autosomal and sex-linked inheritance, this question serves as the perfect application of those concepts. In your study path, we explored how genes located on the X-chromosome exhibit unique inheritance patterns, often bypassing females as carriers and manifesting in males. Royal haemophilia is the classic, textbook example of an X-linked recessive disorder. It earned its "royal" name due to its prevalence in the descendants of Queen Victoria, demonstrating how a mutation on the sex chromosome creates a specific pedigree profile, as detailed in GENETICS by APAC Women's College.

To arrive at the correct answer, you must categorize the location of the gene for each condition. While Tay-Sachs disease and Cystic fibrosis are indeed genetic, they are autosomal recessive conditions. This means the genes are located on non-sex chromosomes (autosomes) and affect both males and females with equal frequency. UPSC often uses these as traps to see if you can distinguish between different modes of inheritance rather than just identifying that a disease is "hereditary." As noted in ScienceDirect: Inheritance, these do not follow the sex-dependent ratios required for the answer.

Finally, Hypertension represents a common UPSC "distractor." Unlike the single-gene (Mendelian) disorders mentioned above, hypertension is multifactorial. It involves a complex interplay of polygenic factors and environmental triggers like diet and stress, rather than being linked to a single gene on a sex chromosome. According to NCBI: Genes and Cardiovascular Disease, it lacks the predictable inheritance pattern of a sex-linked trait. Therefore, by eliminating autosomal and polygenic options, you can confidently conclude that Royal haemophilia is the only sex-linked disease provided.

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