MENDELIAN DISORDER

In humans, Mendelian disorder is a type of genetic disorder primarily resulting due to

alterations in one gene or as a result of abnormalities in the genome. Such a condition
can be seen since birth and be assumed on the basis of family history using the family
tree. The analysis hence carried out is known as pedigree analysis.

In human genetics, pedigree study provides a strong tool, which is utilised to trace the
inheritance of a specific trait, abnormality or disease. Symbols used in pedigree analysis
are:

Each and every feature in any organism is controlled by one or the other gene located on
the DNA present in the chromosome. DNA is the carrier of genetic information which is
transmitted from one generation to the other without any change or alteration.

However, changes or alteration do take place occasionally. Such an alteration or change

in the genetic material is referred to as Mutation. A number of disorders in human beings
have been found to be associated with the inheritance of changed or altered genes or
chromosomes.
Gregor Johann Mendel’s Law of Inheritance:

➢ Gregor Johann Mendel was a scientist who is recognized

as the Father and Founder of Genetics.
➢ Mendel conducted many experiments on the pea plant
(Pisum sativum) between 1856 and 1863.
➢ He studied the results of the experiments and deducted
many observations.
➢ Thus, Laws of Inheritance or Mendel’s Laws of
Inheritance came into existence.

Laws of Inheritance:

Mendel proposed three laws:

• Law of Dominance:

This law states that in a heterozygous condition, the allele whose characters are
expressed over the other allele is called the dominant allele and the characters of this
dominant allele are called dominant characters. The characters that appear in the F1
generation are called as dominant characters. The recessive characters appear in the
F2 generation.

• The Law of Segregation:

The law of segregation states that during the production of gametes, two copies of
each hereditary factor segregate so that offspring acquire one factor from each
parent. In other words, allele (alternative form of the gene) pairs segregate during
the formation of gamete and re-unite randomly during fertilization.
• Law of Independent Assortment:

This means that at the time of gamete formation, the two genes segregate
independently of each other as well as of other traits. Law of independent assortment
emphasizes that there are separate genes for separate traits and characters and they
influence and sort themselves independently of the other genes.

Genetic disorders:

Genetic disorders may be grouped into two categories

1. Mendelian disorders
2. Chromosomal disorders

Mendelian disorders:

➢ Mendelian disorders are mainly determined by alteration or mutation in the single

gene.

➢ These disorders are transmitted to the offspring on the same lines. The pattern of
inheritance of such Mendelian disorders can be traced in a family by the pedigree
analysis.
➢ Most common and prevalent Mendelian disorders are:

1. Haemophilia
2. Cystic fibrosis
3. Sickle cell anaemia
4. Colour blindness
 5. Phenylketonuria
6. Thalassemia

➢ The above mentioned disorders can be classified into two types:

✓ Sex linked recessive disorders

✓ Autosomal recessive disorders

DEFINITION Sex-linked disorder Autosomal disorder

Coded by the genes Coded by the genes located

located on the sex on the autosomes from
chromosome from parents to offspring
CHANCES parents to offspring

Unequal chances Male and female are affected

with equal frequencies
TYPES
Autosomal recessive
Sex-linked recessive Autosomal dominant
Sex-linked dominant
STUDY
Easily studied using a Not easy to study
family pedigree

➢ Out of the disorders mentioned above, Colour blindness and Haemophilia are sex
linked recessive disorders whereas Sickle cell anaemia, Phenyl ketonuria and
Thalassemia are autosomal recessive disorders.

➢ It is important to mention here that such Mendelian disorders may be dominant

or recessive. By pedigree analysis help to understand whether the trait is dominant
or recessive.
 o Sex linked disorders:
A genetic disorder caused by the gene present in the sex chromosome. In humans,
it is caused by the X and Y chromosome. Genes on the X chromosome can be both
dominant and recessive.

A. Colour blindness:
• It is a sex-linked recessive disorder due to defect in either red or green cone of eye
resulting in failure to discriminate between red and green colour.

• The gene responsible for distinguish the colour is X chromosome where in the
dominant form the colours can be identified whereas in the recessive form the
colours cannot be identified

• The colour blind gene is carried on one of the X chromosomes. Since males have
only one X chromosome, if his X chromosome carries a colour blind gene, he will
be suffering from colour blindness.

• In case of females, there are three cases:

I. The two X chromosomes are normal so that she is not suffering from colour
blindness
II. If either one of the X chromosome has colour blindness gene, then the female is
said to be a carrier
III. Rarely, she will inherit a colour blind X from her father and a colour blind X from
her mother and will be suffering from colour blindness.

It occurs in about 8% of males and 0.4% in females because of the presence of only one
X chromosomes in males and two X chromosomes in females.
The mother is not herself colour blind because the gene is recessive. That means that its
effect is suppressed by her matching dominant normal gene.

A daughter will be colour blind, only when her mother is a carrier and her father is colour
blind.
Let’s consider a case where the father is colour blind and the mother is carrier:

If the father of a child is colour blind (XCY) and mother is carrier of colour
blindness (XXC), then probability of the child being colour blind is 50%.

The probability of carrier daughter is 25% and an unaffected son is 25%

Symptoms:

 Rapid eye movement

 Sensitivity towards bright light
 Trouble is seeing colours and the brightness of colours
 The problems in identifying the different between colour shades
  Issues in identifying red and green colours.

B. Haemophilia:
• Haemophilia is a sex linked recessive disorder, which shows its transmission from
unaffected carrier female to some of the male progeny.

• In this disease, a single protein that is a part of the series of proteins involved in
the clotting of blood is affected.

• Due to this, in an affected individual a simple cut will result in non-stop bleeding.
The family pedigree of Queen Victoria shows a number of haemophilic
descendants as she was a carrier of the disease and thus haemophilia is also
referred as The Royal Disease

• The heterozygous female (carrier) for haemophilia may transmit the disease to
sons. The possibility of a female becoming a haemophilic is extremely rare because
mother of such a female has to be a carrier and the father should be haemophilic.
Let’s consider a case where the father is affected with haemophilia and the mother is
carrier:
If the father of a child is Haemophilic (XhY) and mother is carrier of haemophilia (XXh),
then probability of the child (daughter and son) being Haemophilic is 50%.

The probability of carrier daughter is 25% and an unaffected son is 25%

Symptoms:

 Prolonged bleeding from cuts and joints

 Nose bleeding
 Bruising
 Unusual bleeding after vaccinations.
 Pain, swelling or tightness in your joints.
 Blood in your urine

o Autosomal disorders:
Autosomal disorders are due to any mutation in the genes present in the
chromosomes other than allosomes that is in the autosomes.

C. Sickle-cell anaemia:
• This is an autosome linked recessive trait that can be transmitted from parents
to the offspring when both the partners are carrier for the gene.

• This disease is controlled by a single pair of allele, Hb A and HbS.

• The phenotype for the diseased one is Hb SHbS – homozygous.

• Heterozygous individual whose phenotype is Hb A HbS is considered ad carrier
of the disease

• Heterozygous (HbAHbS) individuals appear unaffected but they are carrier of

the disease. So there is 50 per cent probability of transmission of the mutant
gene to the progeny, thus exhibiting sickle-cell trait.

• It converts a GAG codon at sixth position into GUG codon (A sequence of three
consecutive nucleotides)

• The defect is caused by the substitution of Glutamic acid (Glu) by Valine (Val)
at the sixth position of the beta globin chain of the haemoglobin molecule.

• The mutant haemoglobin molecule undergoes polymerisation under low

oxygen tension causing the change in the shape of the RBC from biconcave disc
to elongated sickle like structure
Symptoms:

 Periods of pain that can last a few hours to a few days.

 Blood clots
 Swelling in hands and feet
 Joint pain that resembles arthritis.
 Chronic nerve pain.
 Life-threatening infections.
 Anemia (decrease in red blood cells).

D. Phenylketonuria

• The affected individual lacks an enzyme that converts the amino acid
phenylalanine into tyrosine.

• As a result of this phenylalanine is accumulated and converted into phenyl pyruvic

acid and other derivatives.

• Accumulation of these in brain results in mental retardation.

• These are also excreted through urine because of its poor absorption by kidney
Symptoms:
 Intellectual problems
 Seizures
 Behavioral problems
 Delayed growth
 Skin disorders
 Musty odour in the urine and breath
 A baby born to a mother who has poorly treated
PKU may have the following problems:
• Heart problems
• A small head
• Low birth weight

E. Thalassemia :
• This is also an autosome-linked recessive blood disease transmitted from parents
to the offspring when both the partners are unaffected carrier for the gene.
• The defect could be due to either mutation or deletion which results in reduced
rate of synthesis of one of the globin chains (α and β chains) that make up
haemoglobin.

• People with thalassemia get too much iron in their bodies which result in the
damage to organs like heart, liver and endocrine system

• This leads to the formation of abnormal haemoglobin which leads to anaemia.

➢ There are two types of Thalassemia:

▪ α thalassemia
▪ β thalassemia

α Thalassemia:
• In α thalassemia, the production of α globin chain is affected.

• α thalassemia is controlled by two genes HBA1 and HBA2 of the 16 th chromosome

of each parent

• Thus a person is affected by α thalassemia when one or more of the two genes from
the father and two genes from the mother (total of four genes) is either mutated or
deleted.
 • The more the genes are affected, lesser the production of α globin molecule.

Symptoms:

 Extreme tiredness
 Pale skin
 Shortness of breath & fast heartbeat
 Yellow skin and eyes
 Slow growth
 Change in the shape of face and head bones

β Thalassemia:
• In β thalassemia, the production of β globin chain is affected.
• β thalassemia is controlled by the single gene HBB on the 11th chromosome of each
parent.
• Because of mutation or deletion of the gene HBB, the person is affected by
thalassemia.

Symptoms:
 Tiredness and weakness
 Pale skin
 Poor appetite & abdominal swellings
  Slow growth
 Repeated infections

The main difference between Thalassemia and Sickle cell disorder is that Thalassemia
arises when very few globins are synthesized, whereas Sickle cell disorder arises
because of the synthesis of incorrectly functioning globin.

Conclusion:

Genetic disorders occur as a result of a mutation to DNA. This mutation may affect
whole chromosomes or the specific genes within chromosomes. DNA mutations may
also happen within the DNA of mitochondria, which power a person's cells.

Most genetic conditions are heritable, but some can occur for the first time within the
person who experiences the disorder.

But is some cases, there may be medications available to help slow the progression of a
particular disease.