(3.4) Sickle cell diseases - the most common is sickle cell anaemia (anemia)

Know and understand that some disorders like sickle cell anemia are inherited.

You need to be able to evaluate the outcomes of pedigree analysis when screening for genetic disorders e.g. sickle cell anaemia.

The genetically inherited disorder called sickle cell anemia is described and genetically explained below, and there are serious medical consequences.

 

Genomics and sickle cell anaemia inherited disease

It is now known most of our characteristics are controlled by more than one gene and this is also true for the genetically inherited disease sickle cell anaemia.

Single-gene disorders like sickle cell anaemia comply with what is called 'Mendelian inheritance' and genetic diagrams and Punnett squares are quite easy to work out - as I hope you will see below.

(Most diseases with a 'genetic connection' like diabetes, obesity and cardiovascular diseases (heart disease) involve the interaction of many genes including non-coding sections of the genome's DNA and environmental factors e.g. lifestyle choice - diet and exercise.)

Sickle cell anaemia is a genetic (inherited) blood disorder in which red blood cells (the carriers of oxygen around the body), develop abnormally.

A mutated change in the DNA base sequence of the gene for haemoglobin (has a protein structure) results in abnormal haemoglobin and sickle-shaped red blood cells

Instead of being round and flexible, the sickle red blood cells become shaped like a crescent (hence the name 'sickle').

These abnormal red blood cells can then clog sections of blood vessels (especially the narrow capillaries) leading to pain. These painful effects can last from a few minutes to several months.

The abnormal blood cells have a shorter life-span and are not replaced as quickly as normal healthy red blood cells leading to a shortage of red blood cells, called anaemia.

 

Symptoms of sickle cell anaemia include tiredness, painful joints and muscles and breathlessness, especially after exercise i.e. any extra physical exertion.

The highest frequency of sickle cell disease is found in tropical regions, particularly sub-Sahara Africa, and tribal regions of India and the Middle East.

Although less frequent, sickle cell disease can occur in any population containing people whose ancestors came from the geographical regions mentioned above - it is on the increase in Europe due to current large scale migration from these regions.

 

The connection between sickle cell anaemia and malaria

Malaria is a disease caused by a parasite called Plasmodium which live inside Anopheles mosquitos. When an infected mosquito bites you, parasites are transferred to you, multiply, and make you sick.

People who are heterozygous (Hb^SHb^A) for the sickle cell allele have some resistance to malaria.

In my genetic diagrams below, heterozygous is denoted as the Aa alleles.

Heterozygous people do not show any symptoms but are carriers of the recessive allele.

Carriers, but not sufferers, of the sickle cell anaemia trait (SCT) have some protection against malaria.

During malarial infection, people with SCT have 50-90% less parasites in their blood and get rid of the parasites faster compared to people with normal haemoglobin, so quicker to recover and less likely to die.

The places where malaria is most common are also the places that have the highest percentage of people with SCT. This is not by accident.

Malaria is so deadly that the body came up with a way to fight it via a mutation.

By changing the genetic code of haemoglobin and causing SCT, the carrier has a better chance of surviving a disease with a high death rate, but sickle cell anaemia is still a serious condition.

 

The occurrence of sickle cell anaemia - a faulty allele

For sickle cell anaemia to occur in a child, both parents must carry the recessive allele a for sickle cell disease, but neither is affected by it, but occurrence of the double recessive gene will cause the disease in the offspring.

In the above diagram, imagine the 'arrowed' yellow band represents one of the alleles that codes for red blood cells.

A represents the normal dominant alleles in the pair of chromosomes (notated as AA below in the genetic analysis).

This person is not a carrier or sufferer of sickle cell anaemia.

B represents a dominant normal and a defective recessive allele (notated as Aa below in the genetic analysis).

This person is a carrier, but not a sufferer of sickle cell anaemia because normal is dominant.

C represents a person with a pair of defective recessive alleles (notated as aa below in the genetic analysis).

This person is both a carrier and sufferer of sickle cell anaemia - the double recessive gene prohibits the production of the vital protein.

 

Genetic diagram and Punnett squares for sickle cell anaemia to show how it is inherited

Genetic diagram normal, but carrier of sickle cell anaemia, breeding with another normal, but carrier of the faulty gene

However, there is a 1 in 4 (25%) chance that one of their children will be affected by this genetic disorder - refer to diagram above and Punnett table below, which shows a double recessive allele is needed for the offspring to be affected (genotype aa).

Note

(i) For someone to suffer from sickle cell anaemia, they must inherit the faulty allele (a) from both parents.

(ii) There is a 3 in 4 chance (75%) of offspring being carriers of the recessive allele a, but only 1 in 3 (25%) of these will actually suffer from sickle cell anaemia.

AA = homozygous alleles (dominant)

Aa = heterozygous alleles

aa = homozygous alleles (recessive)

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Five other possible parental crosses involving the recessive allele a for sickle cell anaemia.

I've shown below the analyses for sickle cell anaemia using a basic Punnett square of the two pairs of gametes of the parents and the four possible genotypes of offspring (children).

 

 

4. genotypes of parents: AA x aa			Comments on cross 4. for sickle cell anaemia A non-carrier crossed with someone suffering from sickle cell anaemia. All the offspring will be carriers of the recessive gene a. Non of the offspring will be affected by sickle cell anaemia.
genotypes of children	A	A
a	Aa	Aa
a	Aa	Aa

 

Extra note on sickle cell anaemia:

(i) For 5. AA x AA, all offspring will be AA non affected and non carriers, similarly, for 6. aa x aa, all offspring will be aa affected and all carriers.

(ii) For couples who may carry the recessive gene, certain crosses carry an increased risk that their child might suffer from sickle cell anaemia.

Genetic screening for potentially harmful alleles may inform potential parents of the risk, but this may in itself lead to agonising decisions.

In many poorer countries genetic screening is highly unlikely to be available.

For lots more examples of genetic analysis of offspring see the index with lots of diagrams and explanations.

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Key points Source of information is based on textbooks & syllabus-specifications for students taking the AQA GCSE, Edexcel GCSE and OCR GCSE level biology examinations (~US grades 9-10).

Key points about the genetics of sickle cell anaemia

Sickle Cell Anaemia: Inherited Genetic Disorder and Genetic Outcomes

Sickle cell anaemia is an inherited blood disorder caused by a genetic mutation affecting haemoglobin.

It leads to misshapen red blood cells that reduce oxygen transport.

Understanding its inheritance is important for studying human genetics, disease prevention, and treatment.

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1. What Is Sickle Cell Anaemia?

Sickle cell anaemia is caused by a mutation in the HBB gene, which encodes haemoglobin, the protein in red blood cells responsible for carrying oxygen.

The mutation results in abnormal haemoglobin S, which causes red blood cells to become stiff and sickle-shaped.

Effects of Sickle-Shaped Cells:

• Reduced oxygen transport in the body.

• Blockages in blood vessels, causing pain and organ damage.

• Increased risk of infections and stroke.

• Shorter lifespan for affected red blood cells, leading to anaemia.

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2. Genetic Inheritance of Sickle Cell Anaemia

Sickle cell anaemia follows a recessive inheritance pattern, meaning both parents must pass on the mutated allele for the disease to develop.

Genetic Possibilities:

Parent Genotypes	Possible Offspring Outcomes	Probability
AA (Normal) × SS (Affected)	All offspring carry one sickle cell allele (AS) but are unaffected (carriers).	100% Carrier (AS)
AS (Carrier) × AS (Carrier)	25% Normal (AA), 50% Carrier (AS), 25% Affected (SS)	1 in 4 chance of sickle cell disease
AS (Carrier) × SS (Affected)	50% Carrier (AS), 50% Affected (SS)	1 in 2 chance of sickle cell disease
SS (Affected) × SS (Affected)	100% Affected (SS)	All offspring will inherit the disease

Key Genetic Principles:

• Homozygous recessive (SS): Leads to full sickle cell disease.

• Heterozygous (AS): Carrier status; usually does not show symptoms but can pass on the allele.

• Homozygous dominant (AA): No sickle cell trait or disease.

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3. Importance in Human Genetics

Understanding sickle cell anaemia is crucial for:

• Medical Research & Treatment: Studying gene therapy, bone marrow transplants, and pain management.

• Evolutionary Biology: The sickle cell trait (AS) provides resistance to malaria, making it more common in regions with high malaria prevalence.

• Genetic Screening & Counselling: Helping families understand inheritance risks and reproductive choices.

• Personalized Medicine: Tailoring treatments based on genetic profiles for better patient outcomes.

Sickle cell anaemia demonstrates how genetic inheritance affects human health and evolution.

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Summary of learning objectives and key words or phrases

Know how to explain the genetics cause of the serious medical condition of sickle cell anaemia/anemia.

Know the genetics of the inherited genetic disorder of sickle cell anemia, caused by a faulty gene allele, work out the possible genetic outcomes using Punnett squares and cross bred diagrams for sickle cell anaemia.

For sickle cell anaemia you need to be able to construct genetic diagrams of monohybrid crosses and predict the outcomes of monohybrid crosses and be able to use the terms homozygous (same alleles e.g. AA) genes or heterozygous (different alleles e.g. Aa) and understand the resulting phenotype (gene expression - the outcome!) and genotype (gene type) for sickle cell anaemia.

Know how do you draw monohybrid genetic diagrams for sickle cell anemia.

Know how to construct Punnett squares for monohybrid crosses for sickle cell anaemia.

Be able to predict and/or explain the outcome of crosses between individuals for each possible combination of dominant and recessive alleles of the same gene for the genetic disorder sickle cell anaemia and explain the observed phenotypes from the genotypes of carriers of the genetic disorder sickle cell anaemia.

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