Basic Genetics for Litigators (with Glossary and Illustrations)

Transcription

1 Basic Genetics for Litigators (with Glossary and Illustrations) Raymund C. King, MD, JD For any attorney dealing with genetics issues in the civil or criminal context, a basic understanding of genetic principles will be the key to the successful application of the law to the facts of each unique case. IN THE PAST TWO DECADES, the scientific community has made quantum leaps in understanding human genetics. Currently, more than 4,000 diseases such as sickle cell anemia and cystic fibrosis are known to be genetic and are passed on in families. Modern man is able to understand not only the complex interactions between genes and the environment, but he is also able to identify individuals who are at risk for common diseases. Similarly, the legal community has become more acutely aware of the myriad of legal issues propagated by the scientific advances in genetics. With the help of expert witnesses and objec- Raymund C. King, MD, JD, is with Cowles & Thompson, P.C., in Dallas. This article is based on a paper the author prepared for an August 2002 seminar sponsored by the ABA Tort and Insurance Practice Section. 7

2 8 The Practical Litigator March 2003 tive scientific data, the litigator should be prepared to transform any courtroom into a classroom. This article is designed to assist the litigator and the expert witness with the daunting task of translating complex molecular genetic principles into word pictures and simple analogies for a lay jury. GENES Genes are the chemical messengers of heredity that constitute the blueprint of our biologic makeup. Genes are the legacy of our ancestors, and these genes carry the key to our similarities and differences. Genes are working subunits of DNA (or deoxyribonucleic acid), a chemical information database, that possesses interlocked pairs of chemical bases that are arranged in a unique sequence that determines each individuals qualities. DNA is contained in the central core, or nucleus, of each human cell. Each cell, with the exception of red blood cells, contains a nucleus, and each nucleus contains the same genetic DNA code. Mature red blood cells contain no nucleus. Below is a diagram of a cell with its DNA-containing nucleus: Figure 1 Gene Is Length of DNA At the molecular level, a gene is a length of DNA comprised of 1,000 to 100,000 or more base pairs that has a specific function. The DNA is tightly coiled into groups called chromosomes that reside within the nucleus of the cell. Each human somatic cell has 46 chromosomes that contain the entire genetic blueprint for a human being. In fact, if one took all the DNA contained in a single cell nucleus, and laid each strand end to end, one would end up with a chain almost six feet long and 50 millionths of an inch wide. A human may have anywhere from 50,000 to 100,000 genes. The genetic information is tightly coiled and bound within the nucleus. A single human chromosome, as seen with an ordinary microscope, is about 1/5,000 inch long, yet the DNA molecule in this chromosome is an inch or more in length, compacted into the chromosome by successive coiling and supercoiling. A gene is typically responsible for coding for a particular protein. In humans, the interaction of protein products together result in a chemical reaction or product that ultimately constitutes a human being. Alleles are alternative forms of a gene. They are segments of DNA that code for a particular product or characteristic (e.g., hair color). A locus describes the physical position of an allele on a particular chromosome (i.e., the DNA at a specific location). For example, at a chromosome locus for eye color the allele might result in blue or brown eyes.

3 Basic Genetics 9 Dominant and Recessive Genes A gene will be either dominant or recessive. This means that when two alleles are competing for expression, the dominant gene is always expressed. A recessive gene becomes apparent if its counterpart allele on the other chromosome becomes inactivated or lost. Because each individual has genetic contributions from a mother and a father, there will always be two alternative forms of the gene contained within the DNA pool. In pea plants, for example, the gene that results in tall plants (represented by T ) is dominant over the gene that results in short plants (represented by t ). A pea plant that possesses a big T and a little t (Tt) will appear externally as a tall plant because the big T is the dominant gene. It will have the physical expression, or phenotype, of being a tall plant. If a pea plant possesses only genes for being tall, it will have the genotype TT. If the plant possesses only the genes for being short, it will have the genotype tt. If an individual has two identical alleles (e.g., TT or tt), then the individual is defined as being homozygous. On the other hand, if there are two different alleles (e.g., Tt), then the individual is heterozygous. Punnett Squares If one knows the genotype of a parent pea plant, one can easily predict the probability that a particular phenotype will be expressed by the offspring when the parental units are crossed. For example, the crossing of a tall pea plant with the genotype TT and a short pea plant possessing the genotype tt can be demonstrated diagrammatically by using a Punnett square shown below in Figure 2: Figure 2 From Figure 2, one can see that the mating of a tall plant with the genotype TT and a short plant with the genotype tt will have a 100 percent probability of producing only tall plants. All the offspring will have the phenotype of being tall, but they will have the heterozygous genotype of Tt. Now, let s look at Figure 3 and see what happens when one crosses two phenotypically tall plants with the genotype Tt:

4 10 The Practical Litigator March 2003 Figure 3 The pairing in Figure 3 demonstrates that there will be a 25 percent (or 1 in 4) probability of producing offspring with the genotype TT (tall plants), a 25 percent probability of offspring with the genotype tt (short plants), and a 50 percent probability of offspring with the genotype Tt (tall plants). When we focus upon the phenotypes, however, we see that there is a 75% (or 3 in 4) chance of producing tall plants, but only a 25 percent chance of producing short plants. Humans are much more complex than pea plants, but the same genetic principles apply when dealing with purely dominant and recessive genes. There are also varying degrees of genetic dominance, depending on the allele. However, for the purposes of educating a lay jury about basic genetic principles, it is important to reduce the information to its simplest terms. Bookcase Analogy If one imagines that the genetic material contained in each human cell is a bookcase full of books in a library, then that bookcase would be a dual bookcase with 46 shelves, (i.e., the shelves would be comprised of two stacks of 23 adjacent to each other). Each shelf represents a chromosome. If we labeled one stack of shelves A (mother s genetic contribution) and the other stack B (father s genetic contribution), the bookcase might look something like this: Figure 4

5 Basic Genetics 11 Books contained on the shelves of stack A would come from the mother, and books on the shelves of stack B would come from the father. For a cell to express gene products, our imaginary bookshelf must have an imaginary librarian to act as a messenger who will read the instructions on how to make that gene product. Because each shelf in our example represents a chromosome, each book represents a gene. If a specific book on a specific shelf in stack A gives all the instructions on how to make brown eyes, a similar book in a similar location in stack B will also contain eye information, but may provide directions on how to make blue eyes. These books occupy the same locus, and they are alleles for eye color. Messenger RNA Let s refer to our librarian as a messenger that relays the information to the builders. When our messenger (also known as messenger RNA) comes to read the books on how to express eye color, the messenger will tend to convey the information from the book with the most prominent information, or the dominant book. The dominant gene is expressed, while the recessive gene is not. The book s unique position on the shelf represents the locus where one finds genes for eye color. Some books will provide information on eye color, while other books will provide information on other qualities such as height or propensity for certain diseases. Order of Information Continuing with our analogy, a closer look at one of these books would reveal a very orderly and logical arrangement of information that can be easily read by the messenger. Many good books are divided into chapters, and there is often an introduction section that lets the reader know that the story or work is about to begin. There is also usually a unique ending or conclusion to the book to let the reader know when the story or work is ending. Why the Sequence Matters Similarly, the DNA coding for these genes also demonstrates a specific pattern that allows scientists to determine the exact location (or locus) on a chromosome where a new allele begins and ends. In practice, our ability to determine the exact location where a specific DNA sequence will begin and end is the basis of our ability to employ DNA evidence as a means of identifying or ruling out a suspect. In the same way, our ability to locate specific genes also forms the basis of our understanding of inheritance patterns for certain diseases. Application to Dominant and Recessive Genes A hypothetical application of our genetic knowledge would be as follows: Let s assume that you work for a company that prides itself on its intramural basketball team, and that your company has the reputation for being undefeated because all the employees are over six feet tall. Let s also assume that family members (i.e., children) of the employees are also allowed to play on the teams, and that the employer is so obsessed with winning the company basketball games that he or she only hires tall employees with tall children. (Stop thinking like a lawyer long enough to roll with the hypothetical.) If the employer had access to each employee s DNA data, then theoretically, that employer would be able to screen out any potential employees that carried recessive genes for short stature. Even if the potential employee appeared tall (or had the phenotype of being tall), that individual may carry the recessive gene for short stature, thereby increasing the probability that this individual