Medical Genetics
1. Introduction to Medical Genetics
Medical genetics is an evolving field and our understanding of the genetic contribution of disease is expanding rapidly.
Genetic counseling was also developed to help assist patients who may have genetic diseases or help those in understanding their risks and aid in prevention of genetic diseases. These aspects all come together in the international public effort of the Human Genome Project which set out to determine the sequence of chemical base pairs which make up human DNA to identify and map all of the genes of the human genome from both a physical and functional standpoint. This has provided a wealth of knowledge and technology that can be used to decipher many genetic diseases that affect humans.
The beginning of genetic research originated from the works of Gregor Mendel and his work on peas in the 19th century. His discoveries laid the foundation to understanding genetics and hereditary disease. After many years of refining the science of genetics, technology eventually caught up to theory and the development of molecular genetics, which has revolutionized the field and allowed vast discoveries of human genetics and disease.
Medical genetics can be defined as the scientific study of the inheritance of specific traits and diseases in humans. It is generally considered a field of biology, but recent discoveries have found links between genetic diseases and metabolic disturbances. It is also a very broad field, which can be applied to many different fields such as medicine, but also can be used to understand more about basic science in genetics.
2. Principles of Inheritance
Mendel’s studies were aimed at understanding the patterns of inheritance of the alternative traits. This was done by producing hybrids of the alternative forms and then determining the fate of the traits in the offspring generation. By following several generations of the offspring and carefully recording the results, Mendel was able to come up with precise quantitative conclusions. The general design of Mendel’s experiments involved the crossing of two pure breeding populations, which were P generation, to produce an F1 generation. The F1 generation was then selfed or crossed together to produce the F2 generation. His first studies looked at the inheritance of a single trait of the two alternative forms, such as round and wrinkled seeds. He later studied inheritance of two different traits at the same time, such as seed shape and seed color.
The aim of this section is to describe the biological laws which govern heredity. These laws were first discovered in the 1860s by an Austrian monk, Gregor Mendel, while carrying out inheritance studies of traits in the garden pea. At the time, his work was influential in the world of science and was used as a basis to understand the laws of heredity. Mendel chose the garden pea for his experiments because varieties were available with distinct alternative forms of each trait, such as round versus wrinkled seeds. Also, it was easy to produce a pure breeding population for each trait. A pure breeding population was one in which all individuals had the alternative form of the trait. For example, if round seeds were the dominant trait, a pure breeding population could be produced which only showed the round seed phenotype.
Principles of inheritance. 1- Patterns of inheritance. 2- Chromosome and gene interaction. 3- Genetics and medicine: Mendelian genetics. 4- Genetics and medicine: Probability. 5- The multifactorial nature of inheritance. 6- Genetics and medicine: Quantitative genetics. 7- Clinical cytogenetics: The chromosomal basis of inheritance. 8- Clinical cytogenetics: Disorders of the autosomes and the sex chromosomes.
3. Genetic Disorders and Diseases
Detection of single gene defects is quite specific and is largely dependent on the knowledge of a specific phenotype. Biochemical tests can be carried out to assess the function of a particular protein and can diagnose the disorder in that manner. Other methods include DNA testing and carrier detection. DNA tests compare the DNA sequence of an individual with the normal calculated DNA sequence for any mutations. Carrier detection in family members is carried out by testing gene linkage using DNA markers. DNA markers are highly polymorphic, easily detectable sequences scattered across the genome. They are inherited in a Mendelian fashion, and their special patterns can provide evidence of gene linkage and help predict genetic disease risk for an individual. DNA testing has largely been developed from the Human Genome Project and is one of the most expanding areas of medical genetics.
Single Gene Defects Single gene defects are also known as Mendelian disorders. Most single gene defects are rare and affect 1 in 2000 individuals. They affect both the structure and the function of a protein in an individual. Most single gene disorders are classified into one of four categories: autosomal dominant, autosomal recessive, X-linked, and Y-linked. In each of these categories, the affected protein disrupts the normal biochemical or structural processes in an individual and leads to a clinical abnormality.
Introduction The detection of genetic disorders is one of the major developments within medical genetics in recent years. This is due to the largest amount of morbidity within our population being due to genetic disorders, as well as the significant development in the treatment of genetic disorders. There are three large groups of genetic disorders: single gene defects, chromosomal disorders, and polygenic (or multifactorial) disorders. This chapter will discuss these disorders, as well as their detection and possible methods of treatment.
4. Genetic Testing and Counseling
With the rapid pace of discoveries in human genetics research and the complex interplay between genetics and various inherited disorders, more and more healthcare providers are interested in finding professional help as well as referring their patients to genetic professionals. For example, some physicians feel that they might benefit from having an expert in genetics review a patient’s family history or medical records to assess the possibility of a genetic basis for a health problem. Patients with a personal or family history of a genetic disorder, or women with certain reproductive risks, might seek a genetics professional to obtain a risk assessment or to learn more about available testing options. At other times, healthcare providers and patients seek genetic counseling to obtain a clearer understanding of a complex genetic test result or to learn how a genetic diagnosis or a possible genetic test might impact future health or insurance-related issues.
Genetic testing involves the direct examination of the DNA molecule itself. A scientist who wants to do specific research on DNA can usually obtain the necessary DNA from an individual with a simple and routine procedure such as a blood sample or mouthwash. DNA can also be obtained from cells that are shed in the urine, feces, hair, sweat, and skin. Sometimes it is possible to obtain the DNA in a woman who is pregnant or in a fetus by a procedure called chorionic villus sampling. At no time in the above procedures is it possible to obtain DNA from an individual who is aborted or the pregnancy is terminated.
5. Advances in Medical Genetics
Although it is perhaps early to predict precisely what the future holds, the potential improvements for patients and families affected by genetic disorders are immense.
It is anticipated that during the next decade, the focus of genetic research into common, complex disorders will enable the successful identification of genetic factors, thus opening the doorway to improved treatment and preventative measures. This modern era of genomic medicine will rely heavily on bioinformatics and the development of technology to incorporate genetic findings into the clinical setting.
For those working in genetic science, the year 2003 represented a watershed when the Human Genome Project was completed. The successful sequencing of the entire human genome is one of the most significant accomplishments of the modern scientific era. This accomplishment has already led to many spinoffs, including an attempt to catalogue genetic variations among different populations and identify genetic risk factors for common diseases. Such information is likely to revolutionize medical practice in the future by facilitating a risk assessment and prevention strategy for many disorders.
The immediate future for the discipline of medical genetics is one of rapid expansion. This expansion will involve a greater understanding of genetic events at the molecular level, a refinement of diagnostic techniques as technology develops, and an integration of genetics into all aspects of health care. However, the most important development is likely to be the treatment and prevention of genetic disease through advances in human genetics and the molecular biological sciences.
