Heredity is the transmission of genetic characteristics from ancestor to descendant through the genes. As a subject, it is tied closely to genetics, the area of biological study concerned with hereditary traits. The study of heritable traits helps scientists discern which are dominant and therefore are likely to be passed on from one parent to the next generation. On the other hand, a recessive trait will be passed on only if both parents possess it. Among the possible heritable traits are genetic disorders, but a study in this area is ongoing, and may yield many surprises.
HOW IT WORKS
Heredity and genetics discussed at the beginning of the essay on genetics, the subjects of genetics and heredity are inseparable from each other, but there are so many details that it is extremely difficult to wrap one’s mind around the entire concept. It is advisable, then, to break up the overall topic into more digestible bits. One way to do this is to study the biochemical foundations of genetics as a subject in itself, as is done in Genetics, and then to investigate the impact of genetic characteristics on inheritance in a separate context, as we do here. Also included in the present essay is a brief history of genetic study, which reveals something about the way in which these many highly complex ideas fit together. Many brilliant minds have contributed to the modern understanding of genetics and heredity; unfortunately, within the present context, space permits the opportunity to discuss only a few key figures. The first—a man whose importance in the study of genetics is comparable to that of Charles Darwin (1809-1882) in the realm of evolutionary studies—was the Austrian monk and botanist Gregor Mendel (1822-1884).
For thousands of years, people have had a general understanding of genetic inheritance—that certain traits can be, and sometimes are, passed along from one generation to the next—but this knowledge was primarily anecdotal and derived from casual observation rather than from scientific study. The first major scientific breakthrough in this area came in 1866 when Mendel published the results of a study on the hybridization of plants in which he crossed pea plants of the same species that differed in only one trait. Mendel bred these plants over the course of several successive generations and observed the characteristics of each individual. He found that certain traits appeared in regular patterns, and from these observations, he deduced that the plants inherited specific biological units from each parent. These units, which he called factors, today are known as genes, or units of information about a particular heritable trait. From his findings, Mendel formed a distinction between genotype and phenotype that is still applied by scientists studying genetics. Genotype may be defined as the sum of all genetic input to a particular individual or group, while phenotype is the actual observable properties of that organism. We return to the subjects of genotype and phenotype later in this essay.
MUTATION AND DNA
Although Mendel’s theories were revolutionary, the scientific establishment of his time treated these new ideas with disinterest, and Mendel died in obscurity. Then, in 1900, the Dutch botanist Hugo De Vries (1848-1935) discovered Mendel’s writings, became convinced that his predecessor had made an important discovery, and proceeded to take Mendel’s theories much further. Unlike the Austrian monk, De Vries believed that genetic changes occur in big jumps rather than arising from gradual or transitional steps. In 1901 he gave a name to these big jumps: mutations. Today a mutation is defined as an alteration of a gene, which contains something neither De Vries nor Mendel understood: deoxyribonucleic acid or DNA. Actually, DNA, a molecule that contains genetic codes for inheritance, had been discovered just four years after Mendel presented his theory of factors. In 1869 the Swiss biochemist Johann Friedrich Miescher (1844-1895) isolated a substance from the remnants of cells in pus. The substance, which contained both nitrogen and phosphorus, separated into a protein and an acid molecule and came to be known as nucleic acid. A year later he discovered DNA itself in the nucleic acid, but more than 70 years would pass before a scientist discerned its purpose.
THE DISCOVERY OF CHROMOSOMES
In the meantime, another major step in the history of genetics was taken just two years after De Vries outlined his mutation theory. In 1903 the American surgeon and geneticist Walter S. Sutton (1877-1916) discovered chromosomes, threadlike structures that split and then pair off as a cell divides in sexual reproduction. Today we know that chromosomes contain DNA and hold most of the genes in an organism, but that knowledge still lay in the future at the time of Sutton’s discovery. In 1910 the American geneticist Thomas Hunt Morgan (1866-1945) confirmed the relationship between chromosomes and heredity through experiments with fruit flies. He also discovered a unique pair of chromosomes called the sex chromosomes, which determine the sex of offspring. From his observation that a sex-specific chromosome was always present in flies that had white eyes, Morgan deduced that specific genes reside on chromosomes. A later discovery showed that chromosomes could mutate, or change structurally, resulting in a change of characteristics that could be passed on to the next generation.
DNA MAKES ITS APPEARANCE
All this time, scientists knew about the existence of DNA without guessing its function. Then, in the 1940s, a research team consisting of the Canadian-born American bacteriologist Oswald Avery (1877-1955), the American bacteriologist Maclyn McCarty (1911-), and the Canadian-born American microbiologist Colin Munro MacLeod (1909-1972) discovered the blueprint function of DNA. By taking DNA from one type of bacteria and inserting it into another, they found that the second form of bacteria took on certain traits of the first. The final proof that DNA was the specific molecule that carries genetic information came in 1952 when the American microbiologists Alfred Hershey (1908-1997) and Martha Chase (1927-) showed that transferring DNA from a virus to an animal organ resulted in an infection, just as if an entire virus had been inserted. But perhaps the most famous DNA discovery occurred a year later when the American biochemist James D. Watson (1928-) and the English biochemist Francis Crick (1916-) solved the mystery of the exact structure of DNA. Their goal was to develop a DNA model that would explain the blueprint, or language, by which the molecule provides necessary instructions at critical moments in the course of cell division and growth. To this end, Watson and Crick focused on the relationships between the known chemical groups that compose DNA. This led them to propose a double helix, or spiral staircase, model, which linked the chemical bases in definite pairs. Using this twisted-ladder model, they were able to explain how the DNA molecule could duplicate itself since each side of the ladder contains a compound that fits with a compound on the opposite side. If separated, each would serve as the template for the formation of its mirror image. Autosomes and Sex Chromosomes Genetic information is organized into chromosomes in the nucleus, or control center, of the cell. Human cells have 46 chromosomes each, except for germ, or reproductive, cells (i.e., sperm cells in males and egg cells in females), which each have 23 chromosomes. Each person receives 23 chromosomes from the mother’s egg and 23 chromosomes from the father’s sperm. Of these 23 chromosomes, 22 are called autosomes, or non-sex chromosomes, meaning that they do not determine gender.
The remaining chromosome, the sex chromosome, is either an X or a Y. Females have two Xs (XX), and males have one of each (XY), meaning that females can pass only an X to their offspring, whereas males can pass either an X or a Y. (This, in turn, means that the sperm of the father determines the gender of the offspring.)AllelesThe 44 autosomes have parallel coded information on each of the two sets of 22 autosomes, and this coding is organized into genes, which provide instructions for the synthesis (manufacture) of specific proteins. Each gene has a set locus, or position, on a particular chromosome, and for each locus, there are two slightly different forms of a gene. These differing forms, known as alleles, each represent slightly different codes for the same trait. One allele, for instance, might say “attached earlobe,” meaning that the bottom of the lobe is fully attached to the side of the head and cannot be flapped. Another allele, however, might say “unattached earlobe,” indicating a lobe that is not fully attached and therefore can be flapped.
DOMINANT AND RECESSIVE ALLELES
Each person has two alleles of the same gene—the genotype for a single locus. These can be written as uppercase or lowercase letters of the alphabet, with capital letters defining dominant traits and lowercase letters indicating recessive traits. A dominant trait is one that can manifest in the offspring when inherited from only one parent, whereas a recessive trait must be inherited from both parents in order to manifest. For instance, brown eyes are dominant and thus would be represented in shorthand with a capital B, whereas blue eyes, which are recessive, would be represented with a lowercase b. Genotypes are either homozygous (having two identical alleles, such as BB or bb) or heterozygous (having different alleles, such as Bb). The phenotype, however—that is, the actual eye color—must be one or the other, because both sets of genes cannot be expressed together. Unless there is some highly unusual mutation, a child will not have one brown eye and one blue eye; instead, the dominant trait will overpower the recessive one and determine the eye color of the child. If an individual’s genotype is BB or Bb, that person definitely will have brown eyes; the only way for the individual to have blue eyes is if the genotype is bb—meaning that both parents have blue eyes. Oddly, two parents with brown eyes could produce a child with blue eyes. How is that possible? Suppose both the mother and the father had the heterozygous alleles Bb—a dominant brown and a recessive blue. There is then a 25% chance that the child could inherit both parents’ recessive genes, for a bb genotype—and a blue-eyed phenotype.
LEARNING FROM HEREDITARY LAW
What we have just described is called genetic dominance, or the ability of a single allele to control phenotype. This principle of classical Mendelian genetics does not explain everything. For example, where height is concerned, there is not necessarily a dominant or recessive trait; rather, offspring typically have a height between that of the parents, because height also is determined by such factors as diet. (Also, more than one pair of genes are involved.) The hereditary law does, however, help us predict everything from hair and eye color to genetic disorders. As with the blue-eyed child of brown-eyed parents, it is possible that neither parent will show signs of a genetic disorder and yet pass on a double-recessive combination to their children. Again, however, other factors—including genetic ones—may come into play. For example, Down syndrome (discussed in Mutation) is caused by abnormalities in the number of chromosomes, with the offspring possessing 47 chromosomes instead of the normal 46.
Population genetics studies in heredity and genetics can be applied not only to an individual or family but also to a whole population. By studying the gene pool (the sum of all the genes shared by a population) for a given group, scientists working in the field of population genetics seek to explain and understand specific characteristics of that group. Among the phenomena of interest to population, geneticists are genetic drift, a natural mechanism for genetic change in which specific traits coded in alleles change by chance over time, especially in small populations, as when organisms are isolated on an island. If two groups of the same species are separated for a long time, genetic drift may lead even to the formation of distinct species from what once was a single life-form. When the Colorado River cut open the Grand Canyon, it separated groups of squirrels that lived in the high-altitude pine forest. Over time, populations ceased to interbreed, and today the Kaibab squirrel of the north rim and the Abert squirrel of the south are different species, no more capable of interbreeding than humans and apes. Where humans are concerned, population genetics can aid, for instance, in the study of genetic disorders. As discussed in Mutation, certain groups are susceptible to particular conditions: thus, cystic fibrosis is most common among people of northern European descent, sickle cell anemia among those of African and Mediterranean ancestry, and Tay-Sachs disease among Ashkenazim, or Jews whose ancestors lived in eastern Europe. Studies in population genetics also can supply information about prehistoric events. As a result of studying the DNA in fossil records, for example, some scientists have reached the conclusion that the migration of peoples from Siberia to North America in about 11,000 b.c. took place in two distinct waves. Genetic Disorders There are several thousand genetic disorders, which can be classified into one of several groups: autosomal dominant disorders, which are transmitted by genes inherited from only one parent; autosomal recessive disorders, which are transmitted by genes inherited from both parents; sex-linked disorders, or ones associated with the X (female) and Y (male) chromosome; and multifactorial genetic disorders. If one parent has an autosomal dominant disorder, the offspring have a 50% chance of inheriting that disease.
Approximately 2,000 autosomal dominant disorders have been identified, among them Huntington disease, achondroplasia (a type of dwarfism), Marfan syndrome (extra-long limbs), polydactyly (extra toes or fingers), some forms of glaucoma (a vision disorder), and hypercholesterolemia (high levels of cholesterol in the blood). The first two are discussed in Mutation. Marfan syndrome, or arachnodactyly (“spider arms”), is historically significant because it is believed that Abraham Lincoln suffered from that condition. Some scientists even maintain that his case of Marfan, a disease sometimes accompanied by eye and heart problems, was so severe that he probably would have died six months or a year after the time of his actual death by assassination at age 56 in April 1865.
RECESSIVE GENE DISORDERS
Just as a person has a 25% chance of inheriting two recessive alleles, so two parents who each have a recessive gene for a genetic disorder stand a 25% chance of conceiving a child with that disorder. Among the approximately 1,000 known recessive genetic disorders are cystic fibrosis, sickle cell anemia, Tay-Sachs disease, galactosemia, phenylketonuria, adenosine deaminase deficiency, growth hormone deficiency, Werner syndrome (juvenile muscular dystrophy), albinism (lack of skin pigment), and autism. Several of these conditions are discussed briefly elsewhere, and albinism is treated at length in Mutation. Note that all of the disorders mentioned earlier, in the context of population genetics, are recessive gene disorders. Phenylketonuria (see Metabolism) and galactosemia are examples of metabolic recessive gene disorders, in which a person’s body is unable to carry out essential chemical reactions. For example, people with galactosemia lack an enzyme needed to metabolize galactose, a simple sugar that is found in lactose, or milk sugar. If they are given milk and other foods containing galactose early in life, they eventually will suffer mental retardation.
SEX-LINKED GENETIC DISORDERS
Dominant sex-linked genetic disorders affect females, are usually fatal, and—fortunately—are rather rare. An example is Albright hereditary osteodystrophy, which brings with it seizures, mental retardation, and stunted growth. On the other hand, several recessive sex-linked genetic disorders are well known, though at least one of them, color blindness, is relatively harmless. Among the more dangerous varieties of these disorders, which are passed on to sons through their mothers, the best known is hemophilia, discussed in Noninfectious Diseases. Many recessive sex-linked genetic disorders affect the immune, muscular, and nervous systems and are typically fatal. An example is severe combined immune deficiency syndrome (SCID), which is characterized by a very poor ability to combat infection. The only known cure for SCID is bone marrow transplantation from a close relative. Short of a cure, patients may be forced to live enclosed in a large plastic bubble that protects them from germs in the air. From this sad fact derives the title of an early John Travolta movie, The Boy in the Plastic Bubble (1976), based on the true story of the SCID victim Tod Lubitch. (The ending, in which Travolta, as Tod, leaves his bubble and literally rides off into the sunset with his beautiful neighbor Gina, is more Hollywood fiction than fact. Lubitsch actually died in his early teens, shortly after receiving a bone marrow transplant.)
MULTIFACTORIAL GENETIC DISORDERS
Scientists often find it difficult to determine the relative roles of heredity and environment in certain medical disorders, and one way to answer this question is with statistical and twin studies. Identical and fraternal twins who have been raised in different and identical homes are evaluated for multifactorial genetic disorders. Multifactorial genetic disorders include medical conditions associated with diet and metabolism, among them obesity, diabetes, alcoholism, rickets, and high blood pressure. Other such multifactorial conditions are a tendency toward certain infectious diseases, such as measles, scarlet fever, and tuberculosis; schizophrenia and some other psychological illnesses; clubfoot and cleft lip; and various forms of cancer. The tendency of a particular person to be susceptible to any one of these disorders is a function of that person’s genetic makeup, as well as environmental factors. Breeding within the FamilyIf there is one thing that most people know about heredity and breeding, it is that a person should never marry or conceive offspring with close relatives. Aside from moral restrictions, there is the fear of the genetic defects that would result from close interbreeding. How close is too close? Certainly, first cousins are off-limits as potential mates, though second or third cousins (people who share the same great-grandparents and the same great-great-grandparents, respectively) are probably far enough apart. Hence, the phrase “kissin’ cousins,” meaning a relative who is a distant enough to be considered a potential partner. What kind of defects? Hemophilia, mentioned earlier, is popularly associated with royalty because several members of European ruling houses around the turn of the nineteenth century had it. Common wisdom maintains that the tendency toward the disease resulted from the fact that royalty was apt to marry close relatives. In fact, hemophilia has nothing to do with royalty per se and certainly bears no relation to marriages between close relatives. Research findings gathered over the course of more than three decades, beginning in 1965, indicate that many views about first cousins marrying may be more a matter of tradition than of scientific fact.
According to information published in the Journal of Genetic Counseling and reported in the New York Times in April 2002, first cousins who have children together face only a slightly higher risk than parents who are completely unrelated. For example, within the population as a whole, the risk that a child will be born with a serious defect, such as cystic fibrosis, is 3-4%, while first cousins who conceive a child typically add another 1.7-2.8 percentage points of risk. Although this represents nearly double the risk, it is still a very small factor. Researchers were quick to point out that mating should not take place between persons more closely related than first cousins. According to Denise Grady in the New York Times, “The report made a point of saying that the term ‘incest’ should not be applied to cousins, but only to sexual relations between siblings or between parents and children.” First cousins, on the other hand, are a quite different matter, a fact borne out by the long history of people who married their first cousins. One example was Charles Darwin, who fathered many healthy children with his cousin, Emma Wedgwood.
For any locus, one of two (or more) slightly different forms of a gene. These differing forms mean that alleles code for different versions of the same trait.
AUTOSOMES: The 22 non-sex chromosomes. CHROMOSOME: A DNA-containing body, located in the cells of most living things, that holds most of the organism’s genes. DNA: Deoxyribonucleic acid, a molecule in all cells, and many viruses, that contains genetic codes for inheritance.
DOMINANT: In genetics, a term for a trait that can manifest in the offspring when inherited from only one parent. Its opposite is recessive.
GENE: A unit of information about a particular heritable trait. Usually stored on chromosomes, genes contain specifications for the structure of a particular polypeptide or protein. GENE POOL: The sum of all the genes shared by a population, such as that of species.
GENETIC DISORDER: A condition, such as a hereditary disease, that can be traced to an individual’s genetic makeup.
GENETIC DOMINANCE: The ability of a single allele to control phenotype.
GENOTYPE: The sum of all genetic input to a particular individual or group.
GERM CELL: One of two basic types of cells in a multicellular organism. In contrast to somatic, or body, cells, germ cells are involved in reproduction.
HEREDITY: The transmission of genetic characteristics from ancestor to descendant through the genes.
HETEROZYGOUS: Having two different alleles—for example, Bb.
HOMOZYGOUS: Having two identical alleles, such as BB or Bb.
LOCUS: The position of a particular gene on a specific chromosome.
MUTATION: Alteration in the physical structure of an organism’s DNA, resulting in a genetic change that can be inherited.
NUCLEUS: The control center of a cell, where DNA is stored.
PHENOTYPE: The actual observable properties of an organism, as opposed to its genotype.
RECESSIVE: In genetics, a term for a trait that can manifest in the offspring only if it is inherited from both parents. Its opposite is dominant.
SEX CHROMOSOMES: Chromosomes that determine gender. Human females have two X chromosomes (XX), and males have an X and a Y (XY).
SYNTHESIZE: To manufacture chemically, as in the body.