Genetic Disorders in Humans

Genetic Disorders in Humans

Genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present since birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions.

A genetic disorder may or may not be a heritable disorder. Some genetic disorders transfer from the parents’ genes, but others are always caused by new mutations or changes in the DNA.

Mendelian disorders in humans:

Following are some of the Mendelian disorders in human:


A recessive mutant gene causes thalassemia. This is an autosome linked blood disease. The parents transmit this disease to the offspring. The parents are the carriers of the disease (heterozygous) and remain unaffected. In thalassemia, hemoglobin is not synthesized due to either mutation or deletion causing reduced rate of synthesis of one of the globin chains (i.e., alpha and beta chains). Depending on the chains thalassaemia is of two types i.e, alpha and beta.

This results in the production of abnormal haemoglobin molecules causing anaemia which is the typical symptom of this disease. In homozygous condition, this disease is severe and is termed as thalassemia major that causes the death in the childhood. In heterozygous condition, this disease is mild. It is termed as thalassaemia minor. It is also termed as Cooley’s disease.

Haemoglobin consists of an iron- containing heme ring as well as 4 globin chains- two alpha and two nonalpha. The composition of 4 globin chains determines the haemoglobin type. Fetal haemoglobin (HbF) has two alpha and two gamma chains.

Adult haemoglobin A (HbA) has two alpha and also two beta chains (i.e., alpha2 beta2), whereas haemoglobin A2 (HbA2) has two alpha and also two delta chains.

At birth, HbF accounts for approximately 80% of haemoglobin and HbA accounts for 20%. The transition from gamma globin synthesis to beta globin synthesis begins before birth. By approximately 6 months of age, healthy infants will have transitioned to mostly HbA, a small amount of HbA2 and negligible HbF.

Alpha Thalassemia

It is the result of deficient or no synthesis of alpha globin chains, leading to excess beta globin chains. The two genes (i.e., HBA1 and HBA2) on each chromosome 16 controls the production of alpha globin chain. Deletion of one or more of these genes causes deficient production of alpha globin chain.

Beta Thalassaemia

It is the result of deficient or absence of synthesis of beta globin chains, leading to excess of alpha chains. One gene on each chromosome 11 (HBB) controls the synthesis of beta globin. This disease occurs from any of more than 200 point mutations and (rarely) deletions of the two genes. Beta globin chain production can range from near normal to completely absent leading to varying degrees of excess alpha globin to beta globin chain production.

Sickle Cell Anaemia

The abnormal molecular structure of haemoglobin causes sickle cell anaemia. Thus it is a metabolic disorder. It is inherited through a recessive gene in homozygous condition showing lethal effect. The patients rarely survive to a marriageable age to produce offsprings. In heterozygous condition the recessive gene only partially affects a person. A person with homozygous dominant condition has normal red blood cells. But a person with homozygous recessive condition develops sickle shaped RBC’s. The person dies of chronic anaemia.

Haemoglobin S

Haemoglobin of a normal man consists of four polypeptide chains, containing two identical alpha chains and two identical beta chains. Each alpha and beta chain contains 141 and 146 amino acids respectively. Haemoglobin of a normal adult is haemoglobin A and that from a person with sickle cell anaemia is haemoglobin S. The only chemical difference in these two types of haemoglobins is that in haemoglobin S, valine (i.e., an amino acid) substitutes for glutamic acid (amino acid) at 6th position in alpha chain. Allele for haemoglobin S  here is Hbs (superscript s indicates sickle cell) and the gene for haemoglobin A as HbA (superscript A for normal).

Hbs allele shows many phenotypic effects. The primary effect of Hbgene is the production of an abnormal molecule of haemoglobin. Homozygous persons have severe disease of sickle cell anaemia with retarded physical development, an unusual elongation of arms and legs and they die before the age of maturity.

Heterozygous persons (sickle cell trait) serve as carriers and usually do not suffer from anaemia. They contain only 25 to 40% haemoglobin s which does not permit sickling except under extra ordinary low concentration of oxygen.

The blood of homozygous persons show tall sickle shaped red cells when oxygen tension is lowered.

Heterozygous persons have more resistance to malaria than normal probably because sickle shaped red blood cells do not carry as much space and oxygen as the normal ones and may not supply sufficient oxygen and space for maximum growth of the parasite. Inheritance of sickle cell anaemia follows Mendelian inheritance. Accordingly, heterozygous parents produce children in 1:2 ratio.

Genetic Disorders

Fig: Genetic Disorders (Sickle Cell Anaemia)

Phenylketonuria (PKU)

This is an autosomal recessive disorder. The gene is responsible for the production of phenylalanine hydroxylase (PAH).

Phenylalanine hydroxylase catalyzes conversion of amino acid phenylalanine into tyrosine. Deficiency of hydroxylase results in the increased level of phenylalanine in blood. The deposition in the nervous tissue may also cause mental retardation. Persons with these characteristics suffer from phenylketonuria. It is a recessive trait and is inherited when the gene for the synthesis of enzyme phenylalanine hydroxylase becomes homozygous recessive due to gene mutations. The dominant gene i.e., P controls the synthesis of this enzyme in the liver cells.

A test by Dr.Willard Centrewall  is helpful in detecting the PKU problem in infants . The process involves application of 10% solution of ferric chloride to the wet diaper of the baby . In normal babies yellow spot appears while in PKU children, this spot will be green in colour. One in about 18,000 people inherits PKU.

The PKU patients besides suffering from mental retardness may also show other phenotypic effects such as skin eczema, abnormalities of teeth enamel and bones. Severe restriction in the diet helps a lot in the treatment of the disease. Avoiding foods high in proteins such as meat and egg and consumption of fruits and vegetables in large quantities is also helpful.