Exams Academic Genetic Disorder: Cause, Types, Diagnosis, And Treatment

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
 Genetic Disorder: Cause, Types, Diagnosis, and Treatment
 What is Genetic Disease?
 Types of Genetic Disorder
 1. Single Gene Inheritance
 2. Chromosomal Abnormality
 3. Multifactorial Inheritance
 4. Mitochondrial Inheritance
 Management of Genetic Disease
 Summary
 Frequently Asked Questions (FAQs) on Genetic Disorders
 Latest Updates
 Written BySHILPI SHIKHA
 Last Modified 25-01-2023

Genetic Disorder: Cause, Types, Diagnosis, and

Treatment

Genetic Disorder: Have you heard of a disease called the royal disease? It is
medically known as haemophilia. The name royal disease was given to
haemophilia because the royal family of England was affected by this hereditary
disease. It is believed that Queen Victoria was the carrier of the gene, which her
children inherited, and it led to the death of most male children at a young age
for many generations. It is astounding how a single gene can lead to a fatal
condition for generations. Read along to learn more fascinating things
about genetic disorders, types, diagnosis, and treatment.
What is Genetic Disease?
A genetic disorder or genetic disease is defined as the condition in which disease
appears due to one or more abnormalities in the genome of an individual. A
genetic disease can be inherited from generation to generation. The effect of a
genetic disease can be minor to lethal depending on the gene affected. Genetic
diseases can be caused due to various factors like Single gene mutation, Multiple
gene mutations, environmental factors, Damaged chromosomes, chromosomal
aberration, etc.

Types of Genetic Disorder

A genetic disease can be categorized into four broad categories:

1. Single Gene Inheritance

Single gene inheritance is caused due to mutation in a single gene. These are
also called monogenic disorders, and these genes follow the Mendelian pattern of
inheritance; hence they are often called Mendelian disorders. This disease can be
diagnosed by pedigree analysis.

Single gene inheritance can be of four types: Autosomal dominant, autosomal

recessive, sex-linked dominant, sex-linked recessive.

Fig: Types of Mendelian Disorders

(a) Autosomal Recessive Disease
Autosomal recessive diseases are those where both copies of a mutated gene
located in the autosome are required to affect an individual. If only one copy of a
gene is present, the person becomes a carrier but does not affect the individual.
If one of the parents is affected by this, there is a 25% chance that the child will
be affected.

i. Sickle-cell anaemia: This is an autosomal recessive condition that affects the

clotting of blood. HB A is a normal allele, and the HB s gene is the defective allele.
The three possible genotypes are HBAHBA , HBAHBs, and HBsHBs. The presence of
HBs in homozygous conditions (HB sHBs) causes the disease. The defect occurs due
to single base substitution at the sixth codon of the beta-globin gene from GAG
to GTG, which causes substitution of Glutamic acid (Glu) by Valine (Val) of the
haemoglobin molecule. Due to the mutation, haemoglobin molecules undergo
polymerisation under low oxygen tension resulting in the sickle shape of the RBC.

Fig: Change in Shape of RBC in Sickle Cell Anaemia

ii. Phenylketonuria (PKU): This is an autosomal recessive condition that

results in metabolic errors. The affected individual lacks the
enzyme phenylalanine hydroxylase (PAH). This converts the amino acid
phenylalanine into tyrosine. Due to the absence of enzymes, phenylalanine is
accumulated and converted into phenylpyruvic acid and its other derivatives.
They start to accumulate in the blood and other organs like the brain resulting in
mental retardation. These can be diagnosed by urine samples, as they are
excreted through urine because of their poor absorption by the kidney.
iii. Thalassemia: This is an autosomal recessive blood disorder. Production
of ∝∝ and β� haemoglobin chain is disrupted due to the mutation in HBA1 and
HBA2 genes and HBB genes present on chromosomes 16 and 11, respectively.
Condition with defected ∝∝ chain is called β� thalasseemia and defect
in β� chain is called β� thalassemia. Due to the defects, the quantity of
haemoglobin is reduced.

Fig: Change in Cell Shape in Thalassemia

(b) X-Linked Recessive Disorders

X-linked recessive diseases affect mostly males because even a single copy can
show its impact. If the mother is a carrier of the affected gene, Chances are 50%
of male children will be affected, but no female child will be affected.

i. Colour blindness: It is X -linked recessive disorder that affects males

predominantly. The defective gene affects the cone cells of a person so that he is
unable to differentiate between the colours red and green. The affected gene is
present on the X chromosome. If the mother is a carrier and the father is normal,
50% of male children will be affected while 100% of females will be normal.
 Fig: Pattern of Inheritance in Colourblindness

ii. Haemophilia: Also known as the royal disease, it is also an X -linked

recessive trait that affects males. A single mutation in a clotting protein affects a
person’s ability to clot blood, even for a minor cut. The gene is present on the X
chromosome. The possibility of a female becoming haemophilic is extremely rare
because the mother of such a female has to be at least carrier, and the father
should be haemophilic.

Fig: Inability to Clot Blood in Haemophilia

(c) Sex-Linked Dominant Disease
Sex-linked dominant traits are those present on the sex chromosome (X or Y).
Since it is sex-linked, it has a different impact on different gender. For example,
If the father carries the abnormal X gene, there is a 100% chance that the
daughter will be affected, but none of his sons will be affected. And, if the
mother carries the abnormal X gene, there is a 50% chance that the child, male
or female, will be affected. Example: Rett syndrome

(d) Autosomal Dominant Disease

Autosomal dominant traits are those where a single copy of a mutated gene
located in autosomes is required to affect an individual. If one of the parents is
affected with autosomal dominant traits, there is a 50% chance that the child will
be affected too. Example: Huntington’s disease, Myotonic dystrophy,
Achondroplasia.

2. Chromosomal Abnormality
Chromosomal abnormality includes any change in the number or structure of the
chromosome. Chromosomal abnormality can cause various kinds of diseases.

Change in structure: It includes a change in the structure of the chromosome.

Structural modification may include deletion of a portion of chromosome,
Inversion, duplication, translocation, or deletion. Inversion is a condition where
a segment of the chromosome breaks away and inverts itself. Duplication is a
condition where a segment of the chromosome is duplicated and attached to the
chromosome. In Translocation, a segment of chromosome breaks away and
reattaches itself to another location, and in deletion, a segment of the
chromosome is deleted. Example: Cri-du-Chat Syndrome, Prader-Willi syndrome.
 Fig: Types of Structural Change in Chromosome

Change in number: The number of chromosomes may increase or decrease.

There are mainly two kinds of changes observed in chromosomes – Aneuploidy
and polyploidy
Aneuploidy: It is defined as the condition where the number of chromosomes is
increased or decreased in its haploid set. This condition is caused due to failure
of segregation during anaphase of meiosis, also called nondisjunction. It is
common among humans.
Polyploidy: It is defined as the condition when a completely new set of
chromosomes get added. It results due to chromosomal nondisjunction. These
are rare in humans. Triticum aestivum (wheat) is an example of natural
polyploidy.
Disease caused due to change in chromosome number:

(A) Down’s syndrome

i. Incidence: 1 in every 800 newborns is affected by this condition.
ii. Chromosomal Basis: This disease is caused due to trisomy of 21. The
karyotype of Down syndrome can be written as (47, XX + 21) (females) and (47,
XY +21) (males). The trisomy condition occurs due to the inability of
chromosomes to separate at the time of cell division, also called nondisjunction.

Fig: Idiogram of Downs Syndrome

iii. Symptoms: Symptoms include the flat face, slanting eye, smallmouth,
protruding tongue, flattened nose, short neck, short arms and legs, single deep
crease across the palm, low IQ, stunted growth, muscular hypotonia,
underdeveloped gonads. Down’s syndrome babies also show breathing, heart, or
hearing problems.
iv. Diagnosis and Treatment: This is diagnosed by identifying the presence of
an extra 21st chromosome in the karyotype. There is no standard treatment
procedure discovered yet. This disease can be managed with the help of
counselling, speech therapy, and nutritional supplements.

(B) Turner’s Syndrome

i. Incidence: It occurs in 1 in 2,500 newborns. It is frequently observed in
miscarriages and stillbirths.
ii. Chromosomal basis: Genotype- (45, X). This disease is caused due to
absence of an extra X chromosome in females. The affected individual has 45
chromosomes, i.e., 22 pairs + XO.
iii. Symptoms: Symptoms include short stature, webbed neck, small breasts,
low set ears, swollen hands and feet, rudimentary ovary, sterility, and absence of
secondary sexual characteristics.
 Fig: Symptoms of Turner’s Syndrome

iv. Diagnosis and Treatment: This is diagnosed by the absence of barr body in
the karyotype. There is no standard procedure for treatment. Hormone therapy
like the administration of androgen and estrogen can be prescribed for feminine
development, and counselling is helpful in managing the condition.

(C) Klinefelter’s Syndrome

i. Incidence: It occurs in approximately 1 out of every 1000 newborns.
ii. Chromosomal basis: Genotype: (47, XXY). This condition is caused due to
the presence of an additional copy of the X chromosome. These individuals have
47 chromosomes, i.e., 22 pairs + XXY.
iii. Symptoms: Symptoms include Tall stature, reduced facial and body hair,
coarse voice, smaller testes, Gynaecomastia( Breast development), and sterility.
 Fig: Symptoms of Klinefelter’s Syndrome

iv. Diagnosis and treatment: This condition is diagnosed by the identification

of extra X chromosomes in the karyotypic study. There is no standard treatment
procedure. Some people opt for hormone therapy (testosterone) to develop a
masculine appearance. Counselling is required to manage aggression and
depression associated with it.

3. Multifactorial Inheritance
Multifactorial inheritance is also known as polygenic inheritance. It is a condition
caused due to mutation in multiple genes in combination with environmental
factors. For example,

i. Diabetes mellitus: A common example of multifactorial inheritance, which is

an important example of polygenic disease. It is a heterogeneous group of
disorders that is characterised by persistent high blood sugar levels or
hyperglycemia. India has the largest number of patients worldwide. This
condition can not be permanently cured. However, insulin injections can keep the
sugar level in check.
ii. Breast cancer: It is associated with genes on chromosomes 6, 11, 13, 14, 15,
17, and 22. Other examples: Cancer, Obesity, Diabetes, heart disease, etc.

4. Mitochondrial Inheritance
Mitochondria is a cell organelle associated with ATP production. Mitochondria
possess their own genome made up of roughly 37 genes. Most of these genes are
associated with enzyme production involved in ATP synthesis. Defects in
mitochondrial genes can lead to genetic disorders. Mitochondrial genes can only
be transferred from the mother to the progeny. Example- Leber’s Hereditary
Optic Atrophy (LHON), Myoclonic epilepsy, Mitochondrial encephalopathy, and
Lactic acidosis, etc.
 Fig: Mitochondrial Inheritance

Management of Genetic Disease

Genetic conditions can not be cured permanently, but these can be managed.
The management of different diseases requires different approaches. Inborn
metabolic conditions like PKU can be managed by enzyme replacement therapy.
This can help in reducing the symptoms and help prevent future complications.
Genetic conditions with defective blood cell formation like Thalassemia can be
managed with bone marrow transplantation if performed at an early stage of life.
Some genetic conditions which may affect later parts of life, like cancer, etc., can
be prevented by frequent tests and preventative surgeries. Few difficult
diseases like adenosine deaminase (ADA) deficiency can be managed by gene
therapy.

Although we have various methods to manage many genetic conditions, sadly,

not all conditions can be prevented or treated. Genetic counselling can be used
to predict the chances of occurrence of a genetic condition in a baby or the age
of onset of disease in an individual. Proper diagnosis, genetic counselling, and a
cautious lifestyle can make it easy to deal with genetic conditions.

Summary
Genetic disorders are inborn errors that occur due to defects in the genome. The
genetic condition can be broadly classified into four types: single-gene,
chromosomal, multifactorial, or mitochondrial. Single gene disorders are caused
due to mutation in one gene. Single gene disorders follow Mendelian patterns,
and they can be autosomal dominant, autosomal recessive, X- linked dominant,
or X-linked recessive. Examples of single-gene disorders are haemophilia, Sickle
cell anaemia, Thalassemia, colour blindness, etc. Chromosomal disorders occur
due to change in structure or number of chromosomes.

Down’s syndrome, Klinefelter’s syndrome, and Turner’s syndrome, etc., are

examples of chromosomal disorders. Multifactorial disorders occur due to
multiple genes in combination with environmental conditions. Examples of
multifactorial disorders include cancer, heart disease, etc. Mitochondrial
disorders occur due to mutation in mitochondrial genes. Examples include
Leber’s Hereditary Optic Atrophy (LHON), Myoclonic epilepsy, Mitochondrial
encephalopathy, Lactic acid-osis, etc. Genetic conditions can not be cured, but
they can be managed with a proper approach, genetic counselling, and an
adequate lifestyle.

Frequently Asked Questions (FAQs) on Genetic Disorders

Q.1. Are all genetic disorders inherited?
Ans: No! Not all genetic conditions can be inherited. Some genetic conditions can
occur spontaneously at the time of birth or during embryonic conditions.
Chromosomal abnormalities can not be passed onto another generation.
Q.2. What is the rarest genetic disorder?
Ans: According to the Journal of Molecular Medicine, Ribose-5 phosphate
isomerase deficiency, or RPI Deficiency, is the rarest disease in the world. To
date, there has been only one reported case.
Q.3. What is the most common inherited genetic disorder?
Ans: Sickle cell anaemia is the most common genetic disease.
Q.4. Can genetic disorders be cured?
Ans: Most genetic conditions can not be cured. Only some conditions like cleft
pallet or congenital heart disease can be fully cured. Gene therapy has shown
some promising results, but there are so many genetic conditions that can only
be managed to reduce its effect.
Q.5. How common are genetic abnormalities?
Ans: According to an estimate, one in every 250 adults are affected by genetic
conditions