Genetics and Molecular Medicine

Genetics and molecular medicine are the disciplines in health care that focus on genetic encoding and molecular function within the cell as the foundations for health and disease. Many medical researchers believe nearly every component of health—and correspondingly, every presentation of disease—has some degree of genetic involvement and an individual acquires whatever propensity toward health that his or her genes convey. The manifestations of health and disease in many situations then become a combination of genetics and environment (lifestyle factors). The specialists who diagnose and treat GENETIC DISORDERS are geneticists.

This section, “Genetics and Molecular Medicine,” presents an overview discussion of the structures and functions of human genetics and entries about genetic health and disorders. The entries in this section focus on genetic consequences for health across the spectrum of the body as a whole, including disorders and diseases that affect multiple systems. Entries in other sections of The Facts On File Encyclopedia of Health and Medicine provide detailed content about conditions that result from genetic disorders that affect single body systems. Cross-references connect entries with one another.

Functions of Genetics

Genetics determines every aspect of human existence, from appearance and structure to function. Each individual acquires one set of chromosomes, the molecular presentation of heredity, from each parent. Each complete complement of chromosomes (23 pairs) contains 25,000 to 30,000 genes, the smallest structural and functional units of heredity. Each GENE pair within the structure of a CHROMOSOME has a single and specific task. It accomplishes this task by instructing the cell to make a particular protein, a process called protein encoding. Through protein encoding genes direct every action of every cell.

The genome: the book of life

The complete complement of chromosomes is the human GENOME, quite literally the book of life. The genome contains all of the instructions the body requires to take shape and to function. Within a single individual, every one of the body’s 100 trillion cells contains the same set of chromosomes, so all cells in the body read from the same book of life.

DNA (deoxyribonucleic acid) is the ink of the genome, the biochemical substance that allows the GENETIC CODE to express itself. DNA organizes itself in chemical presentations called nucleotides, which function somewhat like letters. Human DNA presents a surprisingly brief alphabet for the extensive range of genetic expression it permits, forming only four NUCLEOTIDE compounds that subsequently shape the 30,000 or so genes the human genome contains. One of the most intriguing discoveries of the HUMAN GENOME PROJECT is that there are vast amounts of “empty” DNA. Only 1 to 2 percent of DNA encodes. The remaining 98 to 99 percent of DNA is noncoding, much like white space on the printed page of a book. Researchers believe noncoding DNA somehow stabilizes or in other ways supports the structure of DNA within the chromosomes.

Each gene, like a word, contains patterns of nucleotides. Chromosomes, like sentences and paragraphs, present strings of genes that convey integrated and coordinated sets of instructions for specific structures and functions throughout the body. Collectively these genetic instructions are the pages, written in code, that form an individual’s GENOTYPE. The outcome, the individual’s outward presentation of his or her genetic code from appearance to health, is the PHENOTYPE.

Decoding the messages: the cells

The cells decode, interpret, and implement an individual’s genotype. Each gene carries an encoded message that it transcribes to RNA (ribonucleic acid), a carrier molecule within the cell. The RNA conveys the gene’s message to the cell’s ribosomes. Ribosomes are organelles (defined structures with specific functions) within the cell. The job of the ribosome is to translate the gene’s message into a specific protein. The protein then carries the message to its target within the body, which is usually molecular.

Transmitting the code: inheritance patterns

The function of conveying a genotype is as much one of mathematics as biology. INHERITANCE PATTERNS the ways in which genes reorganize into new pairs at CONCEPTION—are the patterns of statistics. A geneticist can calculate with astonishing accuracy the likelihood of certain traits passing from parents to offspring. Such calculations accommodate the potential combinations that can arise from each parent’s genotype.

Health and Disorders of Genetics

In some respects what is perhaps most remarkable about human genetics is the precision and consistency with which myriad, intricate, and complex biochemical actions take place not only to produce a new human being but also to choreograph its functions for eight decades or longer. Though everyone’s genotype contains some mutations, researchers believe most mutations have no consequence for the body’s structure or function. However, understanding of the complex interactions among genes continues to evolve as geneticists engage in further research.

It is a common misperception that there are genes that cause disease, such that there are specific genes for HEMOPHILIA or CYSTIC FIBROSIS in the same fashion as there are certain genes for brown HAIR or green eyes. There are not really “disease” genes, however. There are instead flaws and errors in the structures of certain genes (mutations) that cause them to give the wrong instructions for synthesizing their specific proteins. The consequence is a gap, expansion, or rearrangement in the information. In some situations a gene, or more commonly a segment of or an entire chromosome, is missing—as if pages or chapters are torn from the genetic book of life. In other situations the gene may have extra material or its material is rearranged—as if pages or chapters are inserted into the book. The resulting errors in structure or function can be quite significant.

Researchers have identified more than 6,000 monogenic (single gene) mutations that result in health disorders, affecting 1 child in every 200 born. Among them are CYSTIC FIBROSIS, SICKLE CELL DISEASE, MARFAN SYNDROME, HUNTINGTON’S DISEASE, and HEMOCHROMATOSIS. Other disorders, such as CLEFT PALATE/CLEFT PALATE AND LIP, result from polygenic (multiple gene) mutations or CHROMOSOMAL DISORDERS, such as DOWN SYNDROME. Though as yet there are few treatments to alter the course of genetic and chromosomal disorders, continuing research holds promise that doctors may in the foreseeable future have the ability to offer effective therapeutic interventions.

Traditions in Medical History

In the 1660s English scientist Robert Hooke (1635–1703) used his newest invention, the compound light microscope, to examine a thin slice of cork. The increased magnifying power of this new microscope’s dual lenses was considerable compared to the standard single-lens microscope of the time; and with its improved light source of reflected and focused candlelight, it revealed a level of structure in living organisms scientists had not known existed: the tight clustering of tiny compartments. Hooke called these compartments cells because they reminded him of the living quarters of monks in monasteries. Hooke described his findings and explorations of cells in his 1665 manuscript Micrografia, which became an epochal publication in the field of biology during Hooke’s lifetime short order for such significant recognition.

Not for another 150 years, however, did biologists finally and fully comprehend the interrelationships and organizations of cells within organisms. British botanist Robert Brown (1773–1858) discovered the cell nucleus in 1831, establishing it as the foundation of cell division; 36 years later Swiss biologist and chemist (Johann) Friedrich Miescher (1844–1895) isolated and identified the active protein–acid structure in the cell nucleus responsible for cell division. Miescher called the structure nuclein, and speculated that it not only was the key player in cell reproduction but also was the decanter of heredity itself. Miescher would never know the prophecy of his speculation because the technology to further explore such a hypothesis was still three quarters of a century away.

The words might well have gone from the scientist’s mouth to the monk’s ear, however. Merely a country’s border away Gregor Johann Mendel (1822–1884) spent his days nurturing sweet peas in his monastery’s gardens. Mendel, an Augustinian monk, observed in nature what Miescher studied in the laboratory: the paths of heredity. Mendel crossbred his sweet peas, detailing the patterns of their varieties and alternate characteristics. Mendel would later achieve full recognition for identifying the predictable variations that occurred as the consequence of what he called paired elements of heredity. Less than two years apart these two researchers, the chemist and the botanist, published their respective findings.

In 1933 Thomas Hunt Morgan (1866–1945) received the Nobel Prize in Physiology or Medicine for proving the existence of chromosomes. By the 1940s numerous scientists were trying to unravel the cryptogram of the chromosome. James Watson and Francis Crick, working in collaboration, and Maurice Wilkins, working independently, finally succeeded. In 1953 Watson and Crick unveiled their model of the double-helix structure of deoxyribonucleic acid. DNA, the master code of genetics, was no longer a secret. Watson, Crick, and Wilkins received the 1962 Nobel Prize in Physiology or Medicine “For their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.”

Increasingly sophisticated technology made it possible to study the activity of the cell at the level of the molecule. Following numerous affirming discoveries about genes and DNA sequencing in the 1960s, 1970s, and 1980s, scientists began to talk of sequencing the human genome—unraveling the molecule of heredity. The effort began formally in 1988 with James Watson at the helm of the planning process. Watson saw the Human Genome Project through its official launch in 1990. Only 13 years later, 2 years ahead of schedule and on the 50th anniversary of Watson and Crick’s unveiling of the double helix, the Human Genome Project announced completion of the sequencing of the human genome. “Never would I have dreamed in 1953 that my scientific life would encompass the path from DNA’s double helix to the three billion steps of the human genome,” Watson said in comments to the media at the events celebrating the completion of the Human Genome Project.

Breakthrough Research and Treatment Advances

The high-tech world of genetics and molecular medicine continues to drive the direction of medicine. RECOMBINANT DNA technology debuted in the 1970s, representing a breakthrough in the ability to manipulate synthetic substances such as INSULIN to create products biologically identical to endogenous substances and launching what has become known as the biotech industry. Pharmacogenomics expands the intersection of genetics and pharmacology, with researchers in both disciplines developing customized medications that integrate with an individual’s genotype to produce predictable, reliable, and effective results with minimal potential for adverse DRUG reactions. Many researchers believe aging itself is a function of genetics. Continued work to understand the details of the human genome makes it not only conceivable but likely that on the horizon are therapies to correct genetic mutations and chromosomal errors, and perhaps to overcome the dimensions of aging, that are deleterious to health.

Genetics and molecular medicine open new vistas in medical ethics as well. The line between life-altering treatments and altering life itself becomes increasingly blurred. GENETIC TESTING has the capability to tell not only what is already wrong with a person but what will go wrong in the future, and sometimes even with a timeline. Medical ethicists worry that such information is too much to know and that the risk is high for physicians and their patients (and other parties that have access to the information) to believe the book of life, as it were, is carved in stone rather than set in proteins. Many variables still remain within the control of individuals in regard to health and medical decisions. Environmental interactions—lifestyle factors—can modify most health conditions associated with genetic alterations. Even with all the knowledge arising from the science fiction–like world of genetics and molecular medicine, for many people lifestyle remains the critical turning point between health and disease.

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