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Suggested Citation:"5. GENETIC PRINCIPLES AND ISSUES." Institute of Medicine. 1995. Adverse Reproductive Outcomes in Families of Atomic Veterans: The Feasibility of Epidemiologic Studies. Washington, DC: The National Academies Press. doi: 10.17226/4992.
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Page 27
Suggested Citation:"5. GENETIC PRINCIPLES AND ISSUES." Institute of Medicine. 1995. Adverse Reproductive Outcomes in Families of Atomic Veterans: The Feasibility of Epidemiologic Studies. Washington, DC: The National Academies Press. doi: 10.17226/4992.
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Page 28

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Genetic Principles and :Issues A major underlying concern at issue is whether the exposure to ionizing ra- diation could cause an excess occurrence of genetic disease in the offspring of the Atomic Veterans. There is an intuitive sense in the use of the term genetic disease that is understood by both scientists and the general public for most pur- poses, but the meaning of the term is, in fact, quite elusive when it is needed for the purpose of considering the feasibility of an investigation. Many diseases, in the end, probably result from an interaction of inborn (heritable) susceptibility and a lifelong exposure to various environmental factors. Classically, genetic disease embraces three categories: cytogenetic (chromosomal), single gene, and multifactorial. To be specific, there are some syndromes of multiple malformations that have chromosomal abnormalities (cytogenetic syndromes), such as Down syndrome (which is due to an extra chromosome number 21~. Other diseases are due to defects in single genes and are inherited according to the laws of Mendel, such as familial hypercholes- terolemia, Huntington disease, and neurofibromatosis. Two major patterns of Mendelian inheritance are dominant (disease is seen when one copy of the dis- ease causing gene from one parent is present) and recessive (disease occurs only when two copies of the disease causing genes, one derived from each of the two parents, are present). Finally, many diseases and birth defects, such as diabetes, cancer, infertility, cleft palate or spine bifida, are multifactorial or polygenic (no major gene or single environmental agent is the cause of the disease or birth de 27

28 ADVERSE REPRODUCTIVE OUTCOMES feet). Some birth defects have major environmental determinants, which are called teratogens. Examples include rubella (German measles), which acts di- rectly on the developing human being to cause cataracts, and ionizing radiation, which causes small head size and mental retardation from birth. . The deoxyribonucleic acid (DNA) in each human cell is organized into 46 separate packages called chromosomes that can be seen when the cell is divid- ing, because the chromosomes are condensed into tight particles. Most body cells, called somatic cells, have two sets of chromosomes, one from each parent, for a total of 46 chromosomes in each cell. Sperm and egg cells, which are called germ cells, have just one set of chromosomes. A female has two X chro- mosomes and a male has one X and one Y chromosome; hence, the X and Y chromosomes are called sex chromosomes. The remaining 22 chromosomes are called autosomes. In the normal somatic cell, each gene has two versions, one from the mother (on the chromosome present at fertilization from the egg, the maternal germ cell) and one from the father (on the chromosome from the sperm, the paternal germ cell). Usually, the two genes work in concert to produce normal cellular struc- tures and functions. Sometimes, one or both genes may be so altered that a dis- ease may result. A mutation is a sudden and permanent change in the DNA sequence. Most mutations may have no known effect, but some are harmful and contribute to the occurrence of human disease. Many mutations arise spontaneously, but they may also be caused by exposure to certain chemicals and ionizing radiation. A mutation may change only a single gene (referred to as a point mutation), or may affect the integrity of the chromosome in a manner that involves more than one gene; even the latter type of genetic lesion may not be detectable under the microscope. Ionizing radiation appears to be a poor point mutagen. Many radiation-related mutations are believed to be chromosomal in nature, often in- volving the deletion of a portion of the chromosome.

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Over the past several decades, public concern over exposure to ionizing radiation has increased. This concern has manifested itself in different ways depending on the perception of risk to different individuals and different groups and the circumstances of their exposure. One such group are those U.S. servicemen (the "Atomic Veterans" who participated in the atmospheric testing of nuclear weapons at the Nevada Test Site or in the Pacific Proving Grounds, who served with occupation forces in or near Hiroshima and Nagasaki, or who were prisoners of war in or near those cities at the time of, or shortly after, the atomic bombings. This book addresses the feasibility of conducting an epidemiologic study to determine if there is an increased risk of adverse reproductive outcomes in the spouses, children, and grandchildren of the Atomic Veterans.

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