Management of Genetic Diseases

The management of genetic disease can be divided into  counseling, diagnosis, and treatment. In brief, the  fundamental purpose of genetic counseling is to help theindividual or family understand their risks and options and to empower them to make informed decisions. Diagnosis of genetic disease is sometimes clinical, basedon  the presence of a given set of symptoms, and sometimes molecular, based on the presence of a recognized gene mutation, whether clinical symptoms are present or not. The cooperation of family members may be required to achieve diagnosis for a given individual, and, once accurate diagnosis of that individual has been determined, there may be implications for the diagnoses of otherfamily members. Balancing privacy  issues within a family with the ethical need to inform individuals who are atrisk for a particular genetic disease  can become extremely complex. Although effective treatments exist for some genetic diseases, for others there are none. It is perhaps  this latter set of disorders that raises the most troubling questionswith regard to presymptomatic testing, because  phenotypically healthy individuals can be put in the position ofhearing that they are going to become ill and potentially die and that there is nothing they or anyone else can do to stop it. Fortunately, with time and research, this set of disorders is slowly becoming smaller.

DNA Fingerprinting

DNA fingerprinting, also known as DNA typing, is a method of isolating and making images of sequences of DNA. The technique was developed in 1984 by the British geneticist Alec Jeffreys, after he noticed the existence of certain sequences of DNA (called minisatellites)  that do not contribute to the function of a gene but are repeated within the gene and in other genes of a DNA sample. Jeffreys also determined that each organism  has a unique pattern of these minisatellites, the only exception being multiple individuals from a single zygote (e.g., identical twins). The procedure for creating a DNA fingerprint consists of first obtaining a sample of  cells containing DNA (e.g., from skin, blood, or hair), extracting the DNA, and purifying it. The DNA is then cut at specific points along the strand with substances called restriction enzymes. This produces fragments of varying lengths that are sorted by placing them on a gel and then subjecting the gel toan electric current (electrophoresis): the shorter the fragment the more quickly it will move toward the positive pole (anode). The sorted, double-stranded DNA fragments are then subjected to a blotting technique in which they are split into single strands and transferred to a nylon sheet. The fragments undergo autoradiography in which they are exposed to DNA probes—pieces of synthetic DNA that have been made radioactive and that bind  to the minisatellites. A piece of X-ray film is then exposed to the fragments, and a dark mark is produced at any point where a radioactive probe has become attached. The resultant pattern of these marks can then be analyzed. An early use of DNA fingerprinting was in legal disputes,notably to help solve crimes and to determine paternity. The technique was challenged, however, overconcerns about sample contamination,  faulty preparation procedures, and erroneous interpretation of the results. Efforts were made to improve reliability, and today the technique has been refined through the use of more specific and more sensitive probes and better blotting membranes. It also has been recognized that DNA fingerprinting, similar to other DNA analysis techniques, is limited by the quality of the sample obtained. DNA samples that are degraded or collected postmortem typicallyproduce less reliable results than do samples that are obtained from a living individual. If only a small amount of DNA is available for fingerprinting, PCR may be used to create thousands of copies of a DNA segment. Once an adequate amount of DNA has been produced, the exact sequence of nucleotide pairs in a segment of DNA can be determined using one of several biomolecular sequencing  methods. Automated equipment has greatly increased the speed of DNA sequencing and has made available many practical applications, including pinpointing segments of genes that cause genetic diseases, mapping the human genome, engineering drought-resistant plants, and producing biological drugs from genetically altered  bacteria.

Genetic codes

The genetic code is the set of rules by which a gene is translated into a functional protein. Each gene consists of a specific sequence of nucleotides encoded in a DNA (or sometimes RNA) strand; a correspondence between nucleotides, the basic building blocks of genetic material, and amino acids, the basic building blocks of proteins, must be established for genes to be successfully translated into functional proteins. Sets of three nucleotides, known as codons, each correspond to a specific amino acid or to a signal; three codons are known as "stop codons" and, instead of specifying a new amino acid, alert the translation machinery that the end of the gene has been reached. There are 64 possible codons (four possible nucleotides at each of three positions, hence 43 possible codons) and only 20 standard amino acids; hence the code is redundant and multiple codons can specify the same amino acid. The correspondence between codons and amino acids is nearly universal among all known living organisms.

Genetic Testing

In the case of genetic disease, options often exist for presymptomatic diagnosis—that is, diagnosis of individuals at risk for developing a given disorder, even though at thetime of diagnosis they may be clinically  healthy. Options also may exist for carrier testing, studies that determine whether an individual is at increased risk of having a child with a given disorder, even though he or she personally may never display symptoms.  Accurate predictive information can enable early intervention, which often preventsthe clinical onset of symptoms and the irreversible damage that may have already occurred by waiting for symptoms and then responding to them. In the case of carrier testing, accurate information can enable prospective parents to make more-informed family- planning decisions. Unfortunately, there can also be negative aspects to early detection, including such issues as privacy, individual responses to potentially negative information, discrimination in the workplace, or discrimination in access to or cost of health or life insurance. While some governments have outlawed the use of presymptomatic genetic testing information by insurance companies and employers, others have embraced it as a way to bring spiraling health-care costs under control. Some communities have even considered instituting premarital carrier testing for common disorders in the populace. Genetic testing procedures can be divided into two different groups: (1) testing of individuals considered  atrisk  from phenotype or family history and (2) screening of entire populations, regardless of phenotype or personal family history, for evidence of genetic disorders commonin that population. Both forms are currently  pursued in many societies. Indeed, with the explosion of informationabout the human genome and the   increasing identification of potential “risk genes” for common disorders,such as cancer, heart disease, or diabetes, the role of predictive genetic screening in general medical practice is increasing.

Study of Human Genetics

Some geneticists specialize in the hereditary processes of human genetics. Most of the emphasis is on  understanding and treating genetic disease and genetically influenced ill health, areas collectively known as medical genetics. One broad area of activity is laboratory research dealing with the mechanisms of human gene function and malfunction and investigating pharmaceutical and other types of treatments. Since there is a high degree of evolutionary conservation between organisms, research on model organisms—such as bacteria, fungi, and fruit flies (Drosophila)—which are easier to study, often provides important insights into human gene function. Many single-gene diseases, caused by mutant alleles of a single gene, have been discovered. Two well-characterized single-gene diseases include phenylketonuria (PKU) and Tay-Sachs disease. Other diseases, such as heart disease, schizophrenia, and depression, are thought to have morecomplex heredity components that involve a number of  different genes. These diseases are the focus of a great deal of research that is being carried out today. In addition,abnormalities in chromosomes have been  identified by studies employing techniques such as chromosomal banding. Individual chromosomes are identified by the banding patterns revealed by different staining techniques.Segments of chromosomes or  chromosomes that are aberrant in number and morphology may be precisely identified.Another broad area of activity is clinical genetics, which centres on advising parents of the likelihood of their children being affected by genetic disease caused by mutant genes and abnormal chromosome structure and umber. Such genetic  counseling is based on examining individual and family medical records and on diagnosticprocedures that can detect unexpressed, abnormal forms of genes. Counseling is carried out by physicians with a particular interest in this area or by specially trained nonphysicians.