DNA, Genes And Chromosomes
Did you know that at one point in your career as a human being you were just two little
cells? Those first two cells divided and became four cells, and then eight cells, and so on. Then they rearranged and grouped together to form eyes, lungs and a brain that are like no other person's on earth. How did that happen? The answer lies in your DNA (deoxyribonucleic acid).
You might have heard of DNA, genes and chromosomes, but what are they? How can they determine what we will look like, what our children will be like or what our chances are of developing a disease?
What Is DNA?
DNA is the chemical material you inherited from your parents. It's found in every cell in your body (except for red blood cells). Made up of two long, thin fibers that are twisted together, the uncoiled DNA from a single cell is about 5 feet long. Normally, it could never fit in your cells, so your body bends and compacts it to make it smaller. The tightly coiled pieces of DNA are called chromosomes.
Most people inherit a set of 23 chromosomes from each of their parents (for a total of 46). Each chromosome contains special stretches of DNA called genes. Genes "tell" the cell how to make the thousands of proteins in your body. Your genes are responsible for the millions of activities going on in your body right now.
What Does DNA Do?
Everyone's DNA is slightly different from everyone else's. (Very slightly — 99.9% of our entire DNA is exactly the same. It's the 0.1% that makes each person different.) Compare your hair, eye and skin color to those around you. Your genes have "told" your cells to make certain proteins.
Proteins also help digest food, carry oxygen throughout your body, and attack foreign substances such as bacteria and viruses.
Because your DNA determines how each protein will be made, it is really the structure of your DNA that controls most of your physical features and bodily functions. In other words, your DNA makes you unique, different from every person living now and anyone who has ever existed — unless you are an identical twin. Even identical twins have small differences because individual cells can “read” the DNA into proteins a little bit differently.
DNA And Disease
Think of a string of beads in which the beads are four different colors. DNA is a string of four different chemicals (called nucleotide bases). Each gene, therefore, is also a string of nucleotides. The order in which the four nucleotides appear — called the "sequence" of nucleotides — determines the exact composition of the protein that the gene makes.
Changes in your DNA sequence, called mutations, occur frequently. Many mutations are quickly repaired by the cell. If they are not, some mutations still will have no effect on your proteins. In other cases, mutations will change the way a particular protein is constructed, which could affect its function. Such changes in genes and proteins control why your hair might be curly rather than straight, how tall you are, and why you might be at risk for developing cancer.
That's right: There's a connection between your DNA and some types of diseases you might have now or will have in the future. Cancer, for example, can occur because one or more of your body's proteins are not acting correctly. (They tell your cells to do things they normally wouldn't do — like multiply out of control.) A genetic test can help doctors figure out your chance of developing certain diseases.
What Is DNA Made Of?
DNA is made of four building blocks called nucleotide bases: adenine (A), thymine (T), guanine (G), and cytosine (C). Each strand of DNA is made up of long strings of these four nucleotides arranged in a specific order. Two strands of DNA stick together and twist to form a helix. The two strands stick together because the A and T bases pair up (bond) and the C and G bases pair up. In this way, one strand of DNA is the complement of the other strand.
How Do Proteins Relate To DNA?
Stretches of DNA called genes "tell" the cells in your body how to make thousands of proteins. Proteins are made of amino acids. (There are 20 amino acids. You may have heard them referred to as "building blocks.") To make each protein, amino acids are arranged in a specific order. The order of the amino acids makes one protein different from another, so you can imagine that the correct sequence is very important. The sequence of nucleotides in a gene tells the cell which amino acids to use and how to arrange them. For example, the sequence of the gene for insulin, a protein needed for regulating the amount of sugar in the body, tells the cell exactly how to build the insulin protein. The sequence of the gene tells the cell which amino acid comes first, then second, and then third, and so on, until the entire insulin protein is complete.
What Are "Mutations"?
At one point in your life, you were just two cells. In order to become bigger, your two cells had to divide into four, and then eight and eventually into roughly 50 trillion cells. Each time a cell divides, it makes an extra copy of each chromosome and passes it along to the new cell. This process is called DNA replication.
Right now, many cells in your body are dividing and making extra copies of your DNA. Sometimes your body makes a change during the copying process. These changes are known as mutations. Mutations can occur if your DNA is damaged by exposure to radiation or toxic chemicals. Some mutations help us survive better in our environment. For example, a mutation in a single gene can make a person more resistant to malaria, which is a good thing for people who live in mosquito-infested areas. However, that same mutation in both copies of the gene can cause a very painful disease called sickle cell anemia. Your cells often can repair these mutations in your DNA, but occasionally they are unsuccessful and the mutation remains.
What Kinds Of Mutations Are There?
Think of mutations as changes in the recipe that makes you "you." Adding or removing any ingredient can dramatically change the end result. There are a variety of mutations, but all affect the sequence of your DNA.
Point mutation: This is a single change in one nucleotide: an A might change to a C, for example, or a C to a G. Sometimes a single nucleotide change will not have any effect. Other times, it can change the type of amino acid that is added to the protein, or it can lead to a shortened (truncated) protein. (This is like not cooking your recipe as long as the instructions tell you to.) Sickle cell anemia is an example of a disease caused by point mutations.
Deletion: Part of the DNA sequence — anywhere from one nucleotide to a large section of DNA — is missing. Deletions can cause the cell to use the wrong amino acids to build the protein. Deletions can also shorten the protein. In some cases, a chunk of the protein will be left out. (Imagine leaving out the sugar in a cake recipe.) Many cases of Duchenne muscular dystrophy are caused by deletions.
Insertions: Extra DNA is added to the normal DNA sequence. Similar to deletions, addition of DNA sequence can cause the cell to use the wrong amino acids to build the protein or shorten the protein. In some cases, the protein will have extra amino acids, which could affect protein function. (Try to bake a loaf of bread by adding an improper ingredient, such as liver.)
Inversion: A portion of the DNA sequence is reversed. Inversions can be small or large, and can affect one or more genes. The bleeding disorder hemophilia A is caused by an inversion in the Factor VIII (F8) gene. The effects of an inversion can be similar to those of a deletion or insertion. (The recipe analogy here may be to follow the directions out of order, perhaps mixing the ingredients after they bake.)
Can I Inherit A Mutation?
Some mutations occur in only some of your body’s cells, such as in the cells that make a tumor. These mutations are called "somatic" mutations. They are not passed from parent to child. However, if the DNA in your egg or sperm cells contains a mutation, it can be passed on to your children. These mutations are called "germ-line" mutations, and this is how diseases can run in families.
What Do Dominant And Recessive Mean?
You usually have two copies of every gene: one from your mother and one from your father. Say you inherited a mutated copy of a gene from your father, but a normal or unchanged copy of the same gene from your mother. Depending on the gene, two things can happen.
If it is a dominant mutation, your body cannot work with only the normal protein made from your mother’s gene. In this case, you will have symptoms of the disease, even though you do have one normal gene from your mother. For dominant mutations, you only need to have one mutated copy to have the disease. Some examples of diseases that require only one mutated copy are Huntington's disease, Marfan's syndrome and neurofibromatosis.
If it is a recessive mutation, your body is able to use the one normal protein (made from your mother's normal gene) so well that you will not have symptoms of the disease. In this case, you would be a carrier of the disease, but you wouldn't actually have the disease. It takes two abnormal copies of a recessive gene (one from mom and one from dad) to cause symptoms of the disease. Each of us is a carrier of a few recessive mutations. The chances that our partner will have recessive mutations in the same gene is low for most recessive conditions. In fact, you probably wouldn't even know that you are a carrier of a disease gene, but you could pass it on to your children. And, if the child's other parent also happens to pass on a changed copy of the gene, your child will have two changed copies and they will have the disease.
Most diseases, such as cancer and heart disease, are not inherited this simply. The challenge in genetics will be to develop tests that predict the chance of inheriting complex diseases before symptoms appear.
Illustrations By InteliHealth Designer Lisa Ormerod