SICKLE CELL ANAEMIA(point mutation)

                       SICKLE CELL ANAEMIA(A GENETIC DISORDER)

                                                GENETIC BASIS

Source of figure : PBworks

• HBB gene is responsible for production of HBB protein → present on chromosome no.11 👉on the short arm at 15.5 position at 𝛃 globin locus as shown in figure.
  

• mutation in this gene loci results in defective protein formation. 
• 𝝱 globin gene codes for 𝝱 globin chain of the hemoglobin . Due, to defective 𝝱 gene defective 𝝱 globin chain is formed causing SICKLE CELL ANAEMIA(HBS)

This mutation results in sickle shaped structure of the RBCs and hence the name 👉SICKLE CELL  ANAEMIA.....

                                MOLECULAR BASIS

IN NORMAL HAEMOGLOBIN,

                                          the template strand of the DNA possess CTC gene👉 transcribed to GAG on the RNA strand.

• this GAG codes for glutamic acid (a type of amino acid) at the 6th position on the polypeptide chain during translation process by the use of ribosomal machinery.

HOWEVER, IN SICKLE CELL ANAEMIA,

                                           instead of CTC , there occurs a point mutation in the form of CAC on the template strand of DNA.

• CAC🠊transcribes to GUG
• GUG🠊translates 🠊instead of glutamic acid ;VALINE is inserted at 6th position on the 𝝱 GLOBIN CHAIN OF HAEMOGLOBIN.

VALINE IS A NON-POLAR MOLECULE ,UNLIKE , GLUTAMIC ACID WHICH IS POLAR.

BEING NON- POLAR,THE VALINE MOLECULE DEVELOPS HYDROPHOBIC CONTACT POINT➤ ' STICKY PATCH ' ON THE OUTER SURFACE OF 𝝱 GLOBIN CHAIN OF HBS.

• WHEN DEOXYGENATED,THIS STICKY PATCH ON HBS R.B.C. WILL FORM HYDROPHOBIC INTERACTIONS WITH OTHER DEOXYGENATED HBS R.B.C.
• RESULTING, INTO POLYMERISATION OF DEOXY-HBS FORMING LONG TUBULAR FIBRES.
• THESE INSOLUBLE FIBRES ARE RESPONSIBLE FOR DEFORMING THE SHAPE OF R.B.Cs AS SICKLE SHAPED.

                                                    DISEASE MANIFESTATIONS:

1. VASO-OCCLUSIVE CRISIS: when deoxygenated, the HBS RBCs turned into sickle shaped and clump together causing obstruction to the blood flow through vessels leading to hemolytic anemia.
2. the sickle shaped R.B.Cs also interact with and activate the vascular endothelium, leukocytes and platelets and bind to coagulation factors and plasma proteins forming aggregates that in turn causes Vaso-occlusive crisis and blood stasis.
3. it is a painful condition
4. due to obstruction of blood flow ,hemorrhages and hemolytic anemia occurs.
5. SPLENIC SEQUESTRATION CRISIS :here ,in , due to obstruction caused by blood cells (HBS) the blood pools in the spleen causing the spleen to enlarge .This causes spleen to get bigger which can be felt easily and the hemoglobin count falls.

                      TYPES OF SICKLE CELL DISORDER

• HOMOZYGOUS: where defective gene is inherited from both the parents.
• HETEROZYGOUS: where defective gene is inherited from only one parent.