13.2 Connection between dna and phenotype  (Page 2/3)

Biochemical studies established that the gene affected in sickle-cell ane­mia has the code for an abnormal beta polypeptide, which is one of the components of the hemoglobin molecule. Therefore, there are two different forms of the hemoglobin gene that codes for the beta chain:

• Form 1: Hb ^A has the code for a normal beta chain
• Form 2: Hb ^S has the code for an abnormal beta chain

Hb ^A and Hb ^S are considered alleles. The word “allele” comes from the same root as “alternative.” Thus, alleles are alternative forms of the same gene. Alleles arise by mutation. Mutations come about by many different ways, but what is common among the different types of mutations is a change in the order of nucleotides in the DNA. Thinking back to the Central Dogma of Molecular Biology, one can reword it with the above in mind. Changes in the DNA causes changes in RNA which can cause changes in the polypeptide and a new polypeptide is a new phenotype.

Humans are diploid organisms; they have two copies of most genes. However, the two copies they possess do not have to be identical. When there are two possible alleles for a gene (such as in the gene for the beta chain of hemoglobin), a diploid individual will have one of three possible combinations of the two alleles. They can be Hb ^A Hb ^A , Hb ^A Hb ^S , or Hb ^S Hb ^S .

The set of alleles present in an individual for a given gene is known as the individual’s genotype . The three combinations of two alleles above are therefore the three different genotypes. Individuals that have two copies of the same allele are called homozygous ; individuals with two different alleles are called heterozygous . So, an individual that is Hb ^A Hb ^A is homozygous normal beta chain, an individual that is Hb ^A Hb ^S is heterozygous, and an individual that is Hb ^S Hb ^S is homozygous abnormal beta chain.

There is one more term that you need to know: the expression of the particular combination of alleles an individual has at a locus is known as the individual’s phenotype. The phenotype is really nothing more than the final end product of the genes and their interaction with the environment.

Homozygous Hb ^S Hb ^S individuals (called sickle-cell anemics) can have many sickle-shaped (as opposed to normal disc-shaped) erythrocytes in their blood. How does this occur? The process is well-understood, and summarized below.

In the capillaries (microscopic blood vessels that directly exchange oxygen with the tissues), erythrocytes can be subjected to low oxygen tension after they lose their oxygen to the surrounding tissues. In this low oxygen situation, the abnormal hemoglobin molecules of Hb ^S Hb ^S individuals tend to polymerize (join together), forming stiff, tubular fibers which ultimately distort the shape of the entire erythrocyte, giving it the characteristic “sickle” shape. These sickled cells have a number of effects on the body via two processes.

• 1. The sickle-shape affects capillary blood flow:
• Sickled cells are less able to enter and move through the capillaries.
• Once in the capillaries, they clog capillary flow and cause small blood clots.
• Reduced blood flow results in reduced oxygen availability to the tissues.
• Reduced oxygen supply results in tissue death and damage to vital organs (e.g., the heart, liver and spleen).
• 2. Sickled blood cells have a shorter lifespan than normal red blood cells:
• Reduced lifespan of erythrocytes places a greater demand on the bone marrow to make new red blood cells and on the spleen to break down dead erythrocytes.
• Increased demand on the bone marrow results in severe pain in the long bones and joints.
• Individuals suffering from sickle-cell anemia are frequently ill and generally have a considerably reduced lifespan. These individuals are said to have sickle-cell disease.