GENETICS 101: Technical Terms Explained

The following article is reprinted by permission by the West Plains Daily Quill, dated October 12, 2000.

DNA: "The Book of Life"

Each one of our body's trillions of cells contains DNA, the entire "book" of coded instructions for building and operating the human body. Also called the human genome, the DNA code is made up entirely of chemicals and it controls everything about us -- size, shape, hair and eye color, blood type and so on.

DNA is made up of 46 chromosomes, each structured in the famous double-helix shape. Chromosomes can be compared to "chapters" in the DNA 'book." They come in pairs, 23 of them, with one-half of each pair contributed by the mother, and one-half from the father.

Inside the chromosomes, like pages in a chapter, are many genes, which are encoded instructions that allow a cell to produce a specific product or initiate a specific action. The body houses some 50,000 genes in all.

Each gene is made up of building blocks from only four chemical bases (adenine, thymine, cystosine, and guanine). It is the order of these four chemicals that spells out the instructions to our bodies, much like letters of the alphabet build words and sentences. With a total of about 3.1 billion biochemical "letters" in our DNA, the complexity is truly staggering.

After more than a decade of work, this summer researchers announced the completion of a project the "map the human genome," which means they have recorded the order of practically all 3.1 billion biochemical "letters." But like phrases written in a foreign language, the meaning of the string of letters is still largely unknown. Interpreting the function of the chemical codes is the next step for researchers.

CAUSES OF GENETIC DISEASES

"When genes are working properly, our bodies develop and function smoothly. But should a single gene -- even a tiny segment of a single gene -- go awry, the effect can be dramatic: deformities and disease, even death," explains a National Institutes of Health publication.

At conception, when a gene "goes awry," meaning that the DNA code gets disrupted and doesn't perfectly reproduce, the result is a genetic mutation, a condition new to the child and not passed down from the parents.

"Mutations are always happening," says geneticist Dr. Judith Miles, Columbia. For example, a certain percentage of cases of Duchens muscular dystrophy and Marfan syndrome are new genetic mutations, she said.

Sometimes a whole chromosome, rather than just a gene, gets messed up. Bits of chromosomes can be deleted, or sometimes there's an extra copy of a certain chromosome. Down syndrome is caused by an extra chromosome 21 (making three 21s instead of the typical pair). These spontaneous rearrangements of chromosomes are almost always a new condition, rather than being an inherited trait.

When a mutation occurs within a gene, the new genetic information is embedded in the child's genetic code, and could be passsed down to his or her children. Diseases like cystic fibrosis, sickle cell anemia and hemophilia are typically inherited from parents' genes.

Genes are paired, with each parent contributing one gene to the pair. Some genes are dominant, which means that if a child receives even one copy of the gene, he or she will automatically get the trait for the gene. With recessive genes, a child must inherit one from each parent before the trait will appear.

If a parent is a carrier for a disorder with a dominant gene, the parent will experience the disease, and each one of his or her children has a 50 percent chance of inheriting it. NF (neurofibromatosis) and Huntington disease are passed with dominant genes.

If a disorder is passed in recessive genes, and if both parents are carriers, then there is a one-in-four chance the child could get one such gene from each parent and develop the malady. If only one parent is a carrier, the child cannot develop the disease, but could become a carrier. Cystic fibrosis and sickle cell anemia are examples of diseases passed with recessive genes.

Some children suspected of having a genetic condition turn out to have a disorder resulting from their environment after conception. An expectant mother who contracts a high fever or an infection, or who drinks or takes drugs risks birth defects. Some forms of delayed development can be traced to birth injuries, particularly lack of oxygen, or the inability to take in food during the months after birth, when the brain is growing rapidly.

Genetic physicians have identified and cataloged about 6,000 distinct syndromes that can be attributed to gene mutations, but many of these are extremely rare.

Following is a sample of several of the more common or well-known genetic disorders. While many of the diseases described below can be treated. None can be cured at this time. Since blood tests are available for a number of the listed conditions, prospective parents can determine if they are carriers for those particular diseases.

THE DISEASES

Down Syndrome is one of the most common birth defects, occurring in about one in 800 births. Caused by an extra copy of chromosome 21, children with Down syndrome have some degree of mental retardation; most have eyes that slant up, small ears, small hands, and a small nose and mouth. About 50 percent have congenital heart defects, and many have other special health problems. The risk of bearing a child with Down syndrome increases with the mother's age, from about one in 1,250 at age 25, to one 952 at age 30, one in 378 at age 35 and one in 1076 at age 40.

Sickle cell anemia is the first disease for which a precise genetic blood test was available. The red blood cells of affected individuals can take on a recognizable "sickle" shape. In addition to anemia, people affected by the disease are at risk for frequent infections, experience plugged circulation and bone pain, and at times suffer painful swelling of the hands and feet.

Originating in West Central Africa, as many as 25 percent of the population in that area are carriers of this recessive gene. About 8 percent of American blacks are carriers, resulting in sickle cell disease occurring in about one in every 400 to 600 blacks. Curiously, carriers of the trait have the "selective advantage" of not being susceptible to malaria, and it is believed the high carrier rate was achieved during a long period in areas of the world where malaria is prevalent.

Cystic fibrosis is the most common lethal genetic disease in the northern European Caucasian population, as about one in 25 in that ethnic group carriers this recessive gene, resulting in the disease showing up in about one in 2,000 births. Affected children have sticky viscous secretions in their pancreas and lungs, resulting in chronic lung infections. Research indicated that most people carrying the CF mutation are descended from one common ancestor. If both parents carry the gene, their baby has a one-in-four chance of inheriting the disease, and a 50 percent chance of being an unaffected carrier. A blood test is available for carrier testing.

NF stands for neurofibromatosis. Affecting the nervous system, it's one of the most common hereditary disorders, occurring in one in 4,000 births. NF is characterized by tumors on or under the skin and multiple cafe-au-lait skin spots. In some cases it also can cause learning disabilities, bone deformation, hearing loss or vision impairment. There is no cure, and people who have it can get tumors forming on the nerves anywhere on the body, at any time. Since the gene that carries it is dominant, a parent has a 0 percent chance of passing it on to each of his or her children.

Marfan syndrome affects the connective tissues and skeletal system. Abe Lincoln suffered from the syndrome, and he typifies its carriers, with long thin arms, legs and fingers. Nearsightedness, heart problems and skeletal deformities are also trademarks. Since it has passed through a dominant gene, each child of an affected parent has a 50 percent chance of inheriting the syndrome.

Huntington disease, also passed with a dominant gene, is a late onset disorder that causes personality changes, memory loss, and progressive loss to mental function to the point of dementia. With an average age of onset of 35 to 37 years, most affected individuals do not become ill until they may have already had children. It occurs in about one in 20,000 births. At-risk individuals can be tested at any age.

Duchenne Muscular Dystrophy affects only boys, but the gene that causes this muscular degenerative disease is carried by healthy, unaffected females. The daughter of a carrier has a 50 percent chance of being a carrier herself, and the gene may pass through a series of female carriers before being inherited by a male descendent who contracts the disease. Affected boys usually show muscular weakness before age 5, are wheelchair bound by age 10, and typically die of respiratory complications by the age of 20. The disease incidence is about one in 3,300 male births. Women can be tested to determine if they are carriers.

Like muscular dystrophy, hemophilia affects only boys, and is caused by a gene usually (but not always) passed down through healthy women, Hemophiliacs are deficient in a factor necessary to clot blood, and the disease is characterized by soft tissue bleeding. Once lethal, now it can be treated by blood transfusions and by administering concentrates of the missing blood factor. Carrier testing is available.

Sources for this article include pamphlets provided by the Southern Missouri Regional Genetics Service; interviews with genetics specialist Dr. Judith Miles, Columbia, and genetics counselor Lori Williamson, Mtn. View; the July 3 issue of Time Magazine; and the following books: "Understanding Gene Testing," published by the National Institutes of Health, "Genetics in Medicine," by Margaret Thompson, and "Principles of Medical Genetics," by Thomas Gelehrter and Francis Collins.

This article is reprinted by permission by the West Plains Daily Quill, dated October 12, 2000.