BIology Investigatory Project

Genetic Disorders

Introduction

A genetic disorder is a genetic problem caused by one or more

abnormalities in the genome. Most genetic disorders are quite rare
and affect one person in every several thousands or millions.
Genetic disorders are manly of two types

A. Mendallian Disorders
b. Chromosomal Disorders

Mendallian Disorder
The Mendallian disorder is different types of genetic disorder in
humans. These genetic disorders are mainly caused by the changes
or alterations in a single gene or due to the abnormalities in the
genome.
These conditions will be present since the child’s birth and can be
predicted based on the history of a family with the help of a family
tree. This process of analysis is called the pedigree analysis.
These genetic disorders are quite rare and may affect one person in
every thousands or million. Genetic disorders may be heritable or
may not be heritable. Inheritable genetic disorders, it usually occurs
in the germ line and in non-heritable genetic disorders, the defects
are generally caused by new mutations or due to some changes in
the DNA.
According to the Mendel’s’ laws of inheritance, the different types
of genetic disorders include:
1. Autosomal dominant.
2. Autosomal recessive.
3. Sex-linked dominant.
4. Sex-linked recessive.

Autosomal Dominant
1. Myotonic Dystrophy
Myotonic dystrophy is a long term genetic disorder that affects
muscle function. Symptoms include gradually worsening muscle
loss and weakness.
Muscles often contract and are unable to relax. Other symptoms
may include cataracts, intellectual disability and heart conduction
problems.

Autosomal
Recessive
 1. Sickle Celled Anemia

It is an autosomal linked recessive trait. Sickle cell anemia is

common in persons of African descent and is also found in some
other parts of the world where malaria is, or has been major cause of
death.
Genes are segments of DNA. These genes control protein synthesis.
A conjugated protein found in RBC of man is Hb. It acts as oxygen
transport medium in the blood. Hb is made up of 4 polypeptide
chains of amino acids - 2 α polypeptide and 2 β polypeptide. A mild
change in position of a single amino acid in polypeptide causes
polypeptide changes. The RBC is elongated and forms sickles.
Rupturing of cell may take place and chronic hemolytic anemia is
caused. This disease is caused when gene responsible for
hemoglobin produced by recessive alleles differs in one amino acid
i.e. it incorporates v in place of glutamic acid or substitution of
glutamic acid by valanine at 6th position of β chain leads to
conversion of GAG -----------> GUG.

In heterozygotes HbA HbS, some red cells contain hemoglobin A,

other hemoglobin S. Because both the types of hemoglobin, rather
than a single intermediate form are produced, it is also a case of
codominance.

2. Thalassemia

It an autosome linked recessive blood disease transmitted from

parents to the offspring when

1. Both the partners are unaffected carrier for the gene (or
heterozygous).

2. The defect could be due to either mutation or deletion which

ultimately results in reduced rate of synthesis of one of the
globin chains that make up hemoglobin. This causes the
formation of abnormal hemoglobin.
Alpha α Thalassemia is controlled by two closely linked genes
HBA1 and HBA2 on chromosome 16 of each parent
- It is observed due to mutation or deletion of one or more of the
four genes. The more genes affected, the less alpha globin
molecules produced.

Beta β Thalassemia is
controlled by a single
gene HBB on
chromosome 11 of each
parent.
- It occurs due to
mutation of one or both
the genes. Qualitative
problem of synthesizing an incorrectly functioning globin.

3. Cystic Fibrosis

This genetic disorder is caused by single autosome recessive gene. It

controls an enzyme which produces a glycoprotein. Due to this
glycoprotein, mucus of abnormally high viscosity is produced. Due
to formation of these high viscosity mucus exocrine glands like
sweat glands of skin, lungs, liver and pancreas start functioning
abnormally. It shows symptoms like:

(i) Stagnation of tubules of lungs making it susceptible to

infection. It causes bronchitis.
 (ii) Due to impaired functioning of liver and pancreas, bile
and digestive enzymes of pancreas are produced in less
quantity.

4. Phenylketonuria (PKU)

Phenylketonuria (PKU) is characterized by abnormal increase in

the level of phenylalanine in the blood due to absence of enzyme
phenylalanine hydroxylase. This enzyme is responsible for the
conversion of phenylalanine to tyrosine. If this enzyme is
absent, conversion doesn't happen. Excess of phenylalanine
changes into phenyl pyruvic acid. Much of the phenyl pyruvic
acid is excreted as urine but excess of phenyl pyruvic acid
damages brain and causes mental backwardness in the child. It is
inherited as autosomal recessive trait backwardness in the child.
Sex Linked Recessive

1. Hemophilia
It is a sex linked recessive blood disorder. The factor was
discovered by Judith Pool. In hemophilic blood lacks the capacity to
coagulate. A person suffering from this disease may bleed to death
due to small cut and rarely survive to attain marriageable age. The
factor responsible for blood clotting is anti-hemophilic globulin.
If this factor is absent in the hemoglobin of the blood, even
minor injuries can cause death due to excessive bleeding. Hence it is
known as "bleeder’s disease".
It is also common in royal family of Europe, hence it is known
as "Royal Disease".
The gene responsible for this disease is an "X" linked gene. Thus
single gene in male produces the disease, while 2 genes produce
disease in females. Heterozygous female XhXH is apparently normal
nut actually it is carrier of disease. Carrier female transmits 50%
disease to her sons. This disease is expressed in males, but
transmitted in females. This disease is caused by a recessive gene 'h'
and normal clotting is due to dominant 'H'. Hence various genotypes
are HH, Hh and hh.
2. Colour Blindness
In 1911 Wilson deterred the specific gene for daltonism (colour
blindness) in the X chromosome. This type of mutation is expressed
only in males (about 8%). However, it is rarely reported in females.
This is due to the reason that males have only one X chromosome
and so only one allele for this gene.
So, mutation of this gene expresses a phenotypic change. Due to
colour blindness man cannot distinguish red from green colour.
In females, in heterozygous condition, colour blindness a recessive
trait is not expressed. Females thus can be genetic carriers and are
capable of transmitting colour blindness to progeny. Due to
daltonism, man cannot distinguish red colour from green colour.
Few interesting aspects of colour blindness are:
(a) Males are never carriers.
(b) Colour blindness is more common in males than in
females.
 (c) Colour blind females always have colour blind fathers
and always produce colour blind sons.

Chromosomal Disorder

The chromosomal disorders on the other hand are caused due to

absence or excess or abnormal arrangement of one or more
chromosomes. Failure of segregation of chromatids during cell
division cycle results in the gain or loss of a chromosome(s), called
aneuploidy. For example, Down’s syndrome results in the gain of
ext
ra
co
py
of
chr
om
oso
me
21.
Si
mil
arly, Turner’s syndrome results due to loss of an X chromosome in
human females. Failure of cytokinesis after telophase stage of cell
division results in an increase in a whole set of chromosomes in an
organism and, this phenomenon is known as polyploidy. This
condition is often seen in plants. The total number of chromosomes
in a normal human cell is 46 (23 pairs). Out of these 22 pairs are
autosomes and one pair of chromosomes are sex chromosome
Sometimes, though rarely, either an additional copy of a
chromosome may be included in an individual or an individual may
lack one of any one pair of chromosomes. These situations are
known as trisomy or monosomy of a chromosome, respectively.
Such a situation leads to very serious consequences in the
individual. Down’s syndrome,
Turner’s syndrome, Klinefelter’s syndromes are common examples
of chromosomal disorders.

Autosomal Recessive

1. Patau's Syndrome
It is caused by a trisomy of 13th chromosome in man i.e. 47
chromosome trisomy for 13th chromosome. The abnormality
consists of prominence of the posterior part of the heel cleft lip and
palate or deafness, mental deficiency, malformation of external and
internal organs etc.

2. Cri-du-chat Syndrome

It is due to the deletion of one arm of the 5th autosome. The affected
child, during infancy when it cries, produces a sound resembling the
mewing of a cat. It has widely spaced eyes, epicanthic fold (folds
above the junction of the eye lids), peculiar facial features and
various physical and mental retardations.

Se
x
Linked

1. Klinefelter's Syndrome
 Such persons have 47 chromosomes with one additional X-
chromosome, i.e., 44 + XXY. The person is male with some
feminine characters like enlarged breasts (gynecomastia) one long
limb, degeneracy of seminiferous tubules, sparse body hairs, mental
retardation etc. There may be greater number of X chromosomes 44
+ XY ascertainable by 2 Barr bodies in interphase or 44 +XXY etc.
resulting in skeletal abnormalities, low mental ability etc. The
addition of extra Y leads to 44 + XYY (47) chromosomes. The
males with such condition show above average height and sub-
normal intelligence. They are prone to psychopathic tendencies
Presence of extra X chromosome in females with 44 + XXX: 44 +
XXX etc. will show abnormal sexual developments and mental
retardation Females bear normal genitalia. Such individuals are
sterile.

2. Turner's
Syndrome
It is one of the most common types of female genetic disorder
characterized by hypogonadism. Incidence rates in 25003000 live
female births. It was first discovered by H.H. Turner (1938).
Cause: Karyotype studies showed that genotype of female
suffering from Turner’s syndrome have 45, (44+XO) chromosomes
in which one X-chromosome are less than the normal karyotype. So
the female is monosomic for sex chromosome.
Clinical symptoms: Individual is female but is characterized
by short stature underdeveloped breasts, reduced ovaries and uterus,
no oogenesis and menstrual cycle, little pubic hair mental
retardation, infertility, webbing of neck, peripheral lymphedema,
heavy neck muscles, somatic cells with no sex chromatin etc.
Origin: Turner's syndrome originates from the development of
an abnormal zygote formed by the fusion of abnormal eggs (with no
X-chromosome) and a normal gymnosperm (sperm with X-
chromosome) or due to fusion of a normal egg, (with X-
chromosome and abnormal sperm (with no sex chromosome).