UNIVERSITY OF HEALTH AND ALLIED SCIENCES

CELL BIOLOGY AND GENETICS (SMBM 201)

BSC. MEDICINE (MBCHB)
LEVEL 200

NAME: DZIVENU JULIET ENYONAM

INDEX NUMBER: UHAS20204200

ASSIGNMENT 1
Write short notes on the following genetic disorders highlighting the genetic basis of each
disorder;
Sickle cell disease
Albinism
Thalassemia
Down Syndrome
Turner Syndrome
Cystic Fibrosis
A Genetic Disorder is a condition caused by a mutation in one or more genes that make them
function improperly.
A Genetic basis of a disorder is the extent to which variations or mutations in a person’s genes
causes various disease conditions.

1. Sickle Cell Anemia also known as Sickle Cell Disease (SCD)

This is an inherited or genetic disorder resulting from a point mutation in hemoglobin of the red
blood cells. The hemoglobin contains iron-rich compounds and enables red blood cells to carry
oxygen from the lungs throughout the body. The normal red blood cells which have a bi-concave
shape becomes sickle-like in shape in this disorder, making red blood cells rigid, sticky and
prone to be trapped in small vessels which slows down or cuts off oxygen flow to parts of the
body.
This disorder is an autosomal recessive condition which means two copies of the gene must be
inherited to have the condition, if only one copy of the gene is inherited then one carries the trait
and shows little or no symptoms of the condition. A person is at risk of SCD if both parents carry
the trait for this condition. It can be diagnosed through a blood test; Hemoglobin Electrophoresis
or by Amniocentesis during pregnancy.
The genetic basis of Sickle Cell Disease stems from a missense mutation of one the Beta globin
subunits of the hemoglobin found on chromosome 11 specifically 11p15.5. A normal adult
hemoglobin has two alpha and two beta subunits. The mutated version is called Hemoglobin S,
there is a change of one nitrogenous base from adenine to thymine and a change of amino acid,
Valine takes the place of glutamic acid, this causes mutated proteins to cluster easily in red blood
cells forming the stiff sickle-like shape.
Some symptoms of SCD; Excessive fatigue, Rapid breakdown prematurely of red blood cells
leading to Anemia, Jaundice, Pain crisis and swelling in arms and feet
Common types of sickle cell disease
Hemoglobin SS: this is the most common type with severe and worst symptoms, it occurs when
both copies of hemoglobin S genes are inherited from both parents.
Hemoglobin SC: occurs when you inherit Hb C gene from one parent and Hb S from the other,
anemia in this case is less severe.
Hemoglobin SB+ (beta thalassemia): this affects beta globin, gene production size of red blood
cells reduces because less beta protein is made. If inherited with Hb S one will have beta
thalassemia.
Other rare types are hemoglobin SD, Hemoglobin SE, etc.
SCD can be treated or managed by; Blood transfusion, Bone marrow transplant, Exercises to
reduce stress and crises, Pain medications to relieve pain.
Some complications of SCD are; Severe anemia, Delayed growth, Heart diseases and some
neurological complications such as seizures, stroke.

2. Albinism
An inherited disorder characterized by little or no melanin production, melanin is a component
that determines skin, hair and eye color and also helps in the development of optic nerve. People
with albinism therefore have vision problems, are sensitive to the sun and are at increased risks
of skin cancer. Symptoms include; very pale skin, hair and eye, light sensitivity, rapid eye
movements, vision problems and patches of missing skin pigment.
Albinism is caused by mutations in specific genes and chromosomes responsible for melanin
production and causes different types. It is an autosomal recessive disorder, you need to inherit
two copies of genes for the condition to be expressed, can be inherited if both parents have the
genes or are carriers of the gene
Types of albinism caused by mutations of different genes;
Oculocutaneous albinism (OCA): most common type of albinism, two copies of a mutated gene
are inherited from both parents. A mutation in one of the seven genes labelled OCA1 to OCA7
gives subtypes of OCA. This causes a decreased pigment production in the skin, hair and eyes.
Ocular albinism: this type of albinism is caused by inheriting a mutated form of the GPR143
gene found on the X-chromosome, it is an X-linked recessive condition and predominantly
present in males than females because males have one X-chromosome and therefore inherits one
copy of the mutated gene but females who inherit such gene have a second X-chromosome to
compensate. This condition is mostly limited to the eyes and can be passed on from mother to
her son.
People with this condition can protect themselves by staying out of the sun, wearing sunglasses
and sun-protective clothing.
Complications include eye complications; vision problems can have an impact on learning and
ability to drive, skin complications such as sun burns associated with high risks of skin cancer,
they may also suffer discrimination and emotional problems.

3. Thalassemia
This is an inherited autosomal recessive blood disorder characterized by lees-oxygen producing
protein, hemoglobin and fewer than normal red blood cells in the body. This causes hemolytic
anemia due to decreased or no synthesis of a globin chain.
This disorder is caused by a point mutation in the HBB (hemoglobin beta) gene which makes
instructions for making a protein, beta globin which is a subunit of hemoglobin. This gene is
located on chromosome 11p15.4
A child who inherits two copies of the mutated gene will have the disorder, a person who inherits
only one copy of the mutated form is a carrier or has the trait and lives normally, has a normal
alpha hemoglobin and an abnormal beta thalassemia hemoglobin in the red blood cells. In some
cases, HBB gene mutation is inherited in an autosomal dorminant way in that only one gene is
sufficient to cause beta thalassemia. People mostly affected are people of African, Asian,
Mediterranean and Middle East descent.
Types of thalassemia
There are two types, alpha and beta thalassemia depending on which part of hemoglobin is
lacking.
Alpha thalassemia is caused by mutations in the HBA1 or HBA2 genes or both whiles beta
thalassemia is caused by mutations in the HBB gene, the beta globin chains resulting in excess
alpha chains.
Types of beta thalassemia
There can be mild forms known as thalassemia intermedia, causes milder anemia tat require
rarely blood transfusion, the synthesis of beta chains is less severely reduced in this case.
Major or homozygous thalassemia: the most severe form, requires blood transfusion and
extensive medical care. There is complete absence of beta globin chain synthesis, the two
mutated genes cause the absence of beta gene production. People with this usually show
symptoms like paleness, slow growth, jaundice within the first two years of life. Without
treatment, their spleen, liver and heart soon enlarges causing severe complications, frequent
transfusion keeps hemoglobin levels near normal and prevents complications however repeated
blood transfusions can lead to iron overload causing a buildup that can damage liver, heart and
other organs.
Heterozygous or minor thalassemia: synthesis of only one beta chromosome is reduced, caused
by one normal gene and one mutated one. This causes mild to moderate anemia.
Thalassemia can be tested for prenatally by Chorionic villi sampling around 11th week of
pregnancy, involves removing a tiny part of placenta to be tested or by Amniocentesis around the
16th week by taking a fluid sample surrounding baby for testing.

4. Down Syndrome
This is a chromosomal condition caused by an abnormal cell division resulting in an additional
full or partial copy of chromosome 21, results in three copies of chromosome 21 in each body
cell instead of the usual two copies, it is also referred to as Trisomy 21. It affects 1 in 800 to 1 in
1000 people.
Symptoms of this condition include; development and intellectual delays, mental retardation,
poor muscle tone in infancy, speech delays, hypothyroidism, flat face with bridge of nose, short
body, neck and fingers and increased risks of heart defects, leukemia, digestive problems and
hearing loss.
Risks of this condition increases with an increased maternal age, 35 years and above because
older egg cells have greater risks of improper chromosome division and also being a carrier of
genetic translocation for down syndrome increases one’s risk of passing it on,
Most cases of down syndrome are not inherited, they occur randomly during development of
sperms and egg cells caused by an error in cell division called nondisjunction resulting in the
abnormal number of chromosomes.
It is usually diagnosed by chromo some analysis done on a blood or skin sample to look for an
extra chromosome 21.
Mosaic down syndrome occurs as a random error during cell division in early fetal development
where there are extra number of chromosome 21 in only some body cells.
Translocation down syndrome caused by a rearrangement of genetic material between
chromosome 21 and another chromosome where there are two copies of chromosome 21 but
addition genetic materials of chromosome 21 attaches to the other chromosome, this type of
down syndrome can be inherited.
In down syndrome part of chromosome 21 attaches to another chromosome before or at
conception resulting in two copies of chromosome 21 and an additional copy with genetic
materials of chromosome 21 attached to it.
Treatments for down syndrome include;
Physical therapy for cases involving poor muscle tone in infants
Medical management by a pediatric cardiologist for early repair in babies with heart defects
Surgeries to correct problems of difficulty in swallowing or bowel blockages.

5. Turner Syndrome
This is a chromosomal mutation that alters development in females and results in females
with one of their X chromosome pairs missing or altered. It occurs in about 1 in 2500
births but most common in pregnancies that do not survive to term mostly miscarriages or
still-births.
It is usually not inherited but occurs as a random error during sperm or egg formation
which results in a missing or incomplete set of X chromosomes in females.
The female does not usually have the usual pair of two complete X chromosome, in some
cases they have the two X chromosomes, one incomplete in some of their body cells and
only one X chromosome in other cells, this is called Mosaicism.
 Common symptoms include; usually shorter than average heights, swelling in hands and
feet mostly at birth, kidney problems, webbed necks, broad chest with widely spaced
nipples and are mostly infertile, unable to conceive due to absence of ovarian function or
underdeveloped ovaries.
Turner syndrome can be suspected in pregnancy during and ultrasound test and can be
confirmed by chorionic villi sampling usually done 10-12weeks of pregnancy by taking a
small portion of placenta or by amniocentesis done 16-18 weeks of pregnancy by taking
fluid around the fetus for chromosomal analyses or can be confirmed with a blood test,
Karyotyping. It can also be diagnosed in early childhood with slow growth rates, short
stature, webbed necks or later when puberty does not occur.
Treatments may include; management by a pediatric endocrinologist who is a specialist
in hormones and metabolism, injection of growth hormones, estrogen replacement
therapy usually started at the time of normal puberty and to prevent osteoporosis, Babies
with heart murmurs or aorta narrowing may also need surgeries.

6. Cystic Fibrosis
This is an autosomal recessive disorder caused by an abnormal or mutation in the CFTR
(Cystic Fibrosis Transmembrane Conductance Regulator) found on chromosome 7q31.2
which codes for the CFTR protein which is a protein pump that regulates sodium and
chloride ion movements in and out of cells by active transport, a mutation in this gene affects
mucus producing cells that line the lungs, digestive tract and reproductive organs and affects
mucus, sweat and digestive juices production.
In healthy individuals the CFTR gene allows movement of Na and Cl ions which keeps
mucus thin and easy to be swept away but in Cystic fibrosis with a mutated CFTR gene, not
enough chloride ions are been pumped out, this results in sticky and thick mucus in airways
and pancreatic ducts resulting in the defect.
This disorder is common among white people, 1 in 2500 are born with it whiles 1 in 20 are
carriers, they carry one of the defective gene. It is caused by inheriting two copies of the
defective genes from both parents who have the gene or are carriers.
Symptoms of this disorder include; productive cough, wheezing, chest pains, difficulty in
breathing, salty sweat, lung infections, intestinal blockages and poor weight gain and growth.
There are five classifications of mutation of the CFTR gene;
Class 1 Mutations: Defective Protein Production
Class 2 Mutations: Defective Protein Processing
Class 3 Mutations: Defective Regulation
Class 4 Mutations: Defective Conduction
Class 5 Mutations: Insufficient CFTR protein produced
 Cystic fibrosis can be diagnosed by genetic tests, sputum tests for lung infections, chest X-
rays and CT scans to reveal any swelling in the lungs or sweat chloride test which uses
Pilocarpine a sweat producing chemical.
Some treatment options are; Physical therapy, breathing exercises, use of medications and
antibiotics, lung transplants.
Although cystic fibrosis is fatal, patients live longer and have higher quality of life.

References

https://www.healthline.com

https://www.mayoclinic.org

https://www.genome.gov