Human Genetic Disorders

A genetic disorder is a disease or syndrome that is caused by an abnormality in an individual's DNA. Abnormalities can range from a small mutation in a single gene to the addition or subtraction of an entire chromosome or even a set of chromosomes.

• Genetic disorders are of two types, namely, Mendelian disorders and chromosomal disorders.
• Mendelian disorders are mainly caused by alteration or mutation in the gene. e.g., thalassaemia, sickle cell anaemia, colourblindness, etc.
• On the other hand, chromosomal disorders are caused by the absence or excess of one or more chromosomes or their abnormal arrangement. For e.g., Down’s syndrome, Turner’s syndrome, etc. 

Genetic disorders are caused by problems in genes or chromosomes. These problems include:

1. Chromosomal abnormalities: Changes in the number or structure of chromosomes (e.g., extra or missing chromosomes, or parts being deleted or moved).

2. Gene mutations: changes in the DNA sequence of a gene. Examples include:

• Physical disorders like cleft lip and albinism.
• Physiological disorders like sickle cell anaemia and haemophilia.

Human Chromosomes:

Humans have 46 chromosomes, grouped into 23 pairs. 22 pairs are autosomes (non-sex chromosomes). 1 pair is sex chromosomes (allosomes), which determine gender:

• Females: 44+XX (two X chromosomes).
• Males: 44+XY (one X and one Y chromosome).

Each chromosome has genes that are responsible for specific traits.

Human karyotype (Chromosome chart)

Mendel's experiments revealed two types of genes:

• Dominant genes: traits controlled by these are expressed when present.
• Recessive genes: traits controlled by these are expressed only when both copies of the gene are recessive.

Genetic disorders occur when there are

Mutations in genes (dominant or recessive). Abnormal numbers of chromosomes (e.g., Down syndrome caused by an extra chromosome). These disorders can be passed from parents to children depending on the type of genes (dominant or recessive) and the sex chromosomes involved.

1. Thalassaemia

Thalassaemia is an autosomal, inherited recessive disease. The haemoglobin molecule is made of four polypeptide chains: 2 alpha (D) and 2 beta (E) chains. The synthesis of alpha chains are controlled by two closely linked genes (HBA1 and HBA2) on chromosome 16, while the synthesis of beta chains is controlled by a single gene (HBB) on chromosome 11.

Symptoms: In thalassaemia, a person shows symptoms like anaemia, pale yellow skin, change in size and shape of RBCs, slow growth and development, dark urine, etc. 

2. Down’s Syndrome (21st trisomy)

Down’s syndrome is named after the physician John Langdon Down, who first described this autosomal chromosomal disorder in 1866. This syndrome is caused by an extra copy of chromosome number 21. It shows the presence of three copies of the 21st chromosome instead of a homologous pair. These individuals will have 47 chromosomes instead of the normal number 46. 21st Trisomy occurs due to non-disjunction or failure of separation of chromosomes (autosomes) during gamete formation. 

Symptoms: These patients have mild or moderate mental retardation and skeletal development is poor. Distinct facial features like a small head, ears and mouth; a face that is typically flat and rounded with a flat nose; an open mouth and a protruding tongue, etc. 

Karyotype of Down’s syndrome

3. Turner’s Syndrome: (X monosomy/XO females)

It is a sex chromosomal disorder caused by the non-disjunction of chromosomes during the formation of eggs. Individuals born with Turner’s syndrome have 44 autosomes with XO. They are phenotypically female. 

Symptoms: They have a short stature (height) and webbed neck, a lower posterior hairline, a broad shield-shaped chest, poorly developed ovaries and breasts, and low intelligence. 

Karyotype of Turner’s Syndrome

4. Klinefelter’s syndrome (XXY males)

It is a chromosomal disorder caused by an extra X chromosome in males. Thus, the genotype of individuals is 44 + XXY. They are described as feminised males. An extra chromosome is a result of non-disjunction of the X chromosome during meiosis in the formation of ovum. 

Symptoms: Such an individual is male and has overall masculine development. The voice pitch is harsh and has underdeveloped testis. They are tall with long arms, showing feminine development (development of breast, i.e., gynaecomastia) and no spermatogenesis; therefore, individuals are sterile. 

Karyotype of Klinefelter’s syndrome

• Definition: Genetic disorders are diseases caused by abnormalities in genes or chromosomes.
• Types: They are broadly classified into Mendelian disorders and chromosomal disorders.
• Mendelian Disorders: Caused by a mutation in a single gene; examples include thalassemia, sickle-cell anaemia, colour blindness, haemophilia, and phenylketonuria.
• Chromosomal Disorders: Caused by the absence or excess of chromosomes or structural abnormalities; examples include Down’s syndrome, Turner’s syndrome, and Klinefelter’s syndrome.
• Examples of Effects: Down’s syndrome causes mental retardation; Turner’s syndrome leads to sterile females; Klinefelter’s syndrome causes sterility in males; thalassemia affects haemoglobin production.