From Molecule to Phenotype

How do small changes in DNA molecules affect human traits?

We know that genes are made of DNA and that they interact with the environment to produce an individual organism's characteristics, or phenotype. However, when a gene fails to work or works improperly, serious problems can result.

Molecular research techniques have shown us a direct link between genotype and phenotype. For example, the wax that sometimes builds up in our ear canals can be one of two forms: wet or dry. People of African and European ancestry are more likely to have wet earwax—the dominant form. Those of Asian or Native American ancestry most often have the dry form, which is recessive. A single DNA base in the gene for a membrane-transport protein is the culprit. A simple base change from guanine (G) to adenine (A) causes this protein to produce dry earwax instead of wet earwax.

The connection between molecule and trait, and between genotype and phenotype, is often that simple, and just as direct. Changes in a gene's DNA sequence can change proteins by altering their amino acid sequences, which may directly affect one's phenotype. In other words, there is a molecular basis for genetic disorders.

Disorders Caused by Individual Genes Thousands of genetic disorders are caused by changes in individual genes. These changes often affect specific proteins associated with important cellular functions.

▸ Sickle Cell Disease This disorder is caused by a defective allele for beta-globin, one of two polypeptides in hemoglobin, the oxygen-carrying protein in red blood cells. The defective polypeptide makes hemoglobin a bit less soluble, causing hemoglobin molecules to stick together when the blood's oxygen level decreases. The molecules clump into long fibers, forcing cells into a distinctive sickle shape, which gives the disorder its name.

Sickle-shaped cells are more rigid than normal red blood cells, and, therefore, they tend to get stuck in the capillaries—the narrowest blood vessels in the body. If the blood stops moving through the capillaries, damage to cells, tissues, and even organs can result.