We now focus on conditions caused by an extra chromosome or a single destructive gene. Three factors make these conditions relevant to human development:

As you know, each sperm or ovum usually has 23 chromosomes, creating a zygote with 46 chromosomes and eventually a person. However, cells do not always split exactly in half to make those reproductive cells.

One variable known to correlate with chromosomal abnormalities is the parents’ age, particularly the age of the mother. A suggested explanation is that, since ova begin to form before a girl is born, older mothers have older ova. When the 46 chromosomes of the mother make ova, usually the split is even, 23/23. But older women are more likely to have some ova that have 22 or 24 chromosomes. Sperm also are diminished in quantity and normality as men age.

Miscounts are not rare. One estimate is that 5 to 10 percent of all zygotes have more or fewer than 46 chromosomes (Brooker, 2009); another estimate suggests that the rate is as high as 50 percent (Fragouli & Wells, 2011). Estimates vary because no one knows for certain. Almost all abnormal zygotes fail to duplicate, divide, differentiate, and implant, or are spontaneously aborted before a woman even knows she is pregnant. Thus an accurate count of zygotes with extra chromosomes is impossible to obtain.

If implantation does occur, many zygotes with chromosomal miscounts are aborted, either spontaneously (miscarried) or by choice. It is estimated that the abortion rate for such zygotes is about 5 percent. Ninety-nine percent of newborns have the usual 46 chromosomes, but for those who do not, birth is hazardous.

About 5 percent of stillborn (dead at birth) babies have 47 chromosomes (Miller & Therman, 2001), and many other babies with 47 chromosomes die within the first few days. Only once in about every 200 births does a newborn survive with 45, 47, or, rarely, 48 or 49 chromosomes.

Survival is much more common if some of the cells have 46 chromosomes and some 47, a condition called mosaicism, or if the problem does not involve a whole chromosome but only a missing or extra piece of a chromosome. Overall, advanced analysis suggests mosaicism “may represent the rule rather than the exception” (Lupski, 2013, p. 358). We may all be mosaics, some more than others. Usually this has no detectable effect on development, although it seems as if cancer is more likely if a person has extra or missing genetic material.

If an entire chromosome is missing or added, that leads to a recognizable syndrome, a cluster of distinct characteristics that tend to occur together. Usually the cause is three chromosomes at a particular location instead of the usual two (a condition called a trisomy). The most common extra-chromosome condition that results in a surviving child is Down syndrome, also called trisomy-21 because the person has three copies of chromosome 21.

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Some 300 distinct characteristics can result from that third chromosome 21. No individual with Down syndrome is identical to another, but trisomy-21 usually produces specific physical characteristics—a thick tongue, round face, and slanted eyes as well as distinctive hands, feet, and fingerprints.

Many people with Down syndrome also have hearing problems, heart abnormalities, muscle weakness, and short stature. They are usually slower to develop intellectually, especially in language, and they reach their maximum intellectual potential at about age 15 (Rondal, 2010). Some are severely intellectually disabled; others are of average or above-average intelligence. That extra chromosome affects the person lifelong, but family context, educational efforts, and possibly medication can decrease the harm (Kuehn, 2011).

Every human has at least 44 autosomes and one X chromosome; an embryo cannot develop without those 45. However, about 1 in every 500 infants is born with only one sex chromosome (no Y) or with three or more (not just two) (Hamerton & Evans, 2005); the particular combination of sex chromosomes results in specific syndromes (see Table 3.2).

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Having an odd number of sex chromosomes impairs cognition and sexual maturation, with varied specifics depending on epigenetics (Hong & Reiss, 2014). It is not unusual for an affected person to seem to be developing normally until they find they are infertile. Then diagnosis reveals the undetected problem.

Everyone carries alleles that could produce serious diseases or handicaps in the next generation. Most such genes have no serious consequences because they are recessive. The phenotype is affected only when the inherited gene is dominant or when a zygote is homozygous for a particular recessive condition, that is, when the zygote has received the recessive gene from both parents.

Most of the 7,000 known single-gene disorders are dominant (always expressed) (Milunsky, 2011). Severe dominant disorders are rare because people with such disorders usually die in childhood and thus do not pass the gene on to children.

Severe dominant disorders become common only when they are latent in childhood, manifest in adulthood. That is the case with Huntington disease, a fatal central nervous system disorder caused by a copy number variation—more than 35 repetitions of a particular set of three base pairs. The symptoms first appear in middle age, when some people have had several children, as did the original Mr. Huntington. Half of them inherited his dominant gene, which is why the disease is named after him.

Another exception to the general rule that serious dominant diseases are not inherited is a rare but severe form of Alzheimer’s disease. It causes dementia before age 60. Most forms of Alzheimer’s, which begin after age 70, are not dominant.

Severe recessive diseases are more numerous because they are passed down from one generation to the next by carriers who do not know they carry the recessive gene. Some such recessive conditions are X-linked, including hemophilia and Duchenne muscular dystrophy.

Fragile X syndrome is caused by more than 200 repetitions on one gene (Plomin et al., 2013). (Some repetitions are normal, but not this many.) The cognitive deficits caused by fragile X syndrome are the most common form of inherited intellectual disability (many other forms, such as trisomy-21, are not usually inherited). Boys are much more often impaired by fragile X than are girls.

Most recessive disorders are on the autosomes, not the X or Y (Milunsky, 2011). Carrier detection is possible for about 500 of them, and diagnosis of the actual disorder is possible for thousands of them, creating an ethical dilemma. Should someone be told about a genetic disorder if no treatment is available and if the knowledge will not change anything?

Some recessive diseases are very common, and that has led to research and effective treatment. About 1 in 12 North American men and women carries an allele for cystic fibrosis, thalassemia, or sickle-cell disease, all devastating in children of both sexes. That high incidence occurs because carriers have benefited from the gene, although the double recessive is harmful.

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To explain this benefit, consider the most studied example: sickle-cell anemia. Carriers of the sickle-cell gene die less often from malaria, which is prevalent in parts of Africa. Indeed, four distinct alleles cause sickle-cell anemia, each originating in a malaria-prone region.

Selective adaptation allowed the gene to become widespread because it protected more people (the carriers) than it killed (those who inherited the recessive gene from both parents). Odds were that if a couple were both carriers and had four children, one would die of sickle cell, one would not be a carrier and thus might die of malaria, but two would be carriers. These carriers would not only develop normally but they would also have added protection against a common, fatal disease, and thus they would be likely to become parents themselves. In that way, the recessive trait became widespread.

Almost every disease and risk of death is more common in one ethnic group than in another (Weiss & Koepsell, 2014). About 11 percent of Americans with African ancestors are carriers of the sickle-cell gene; cystic fibrosis is more common among Americans with ancestors from northern Europe because carriers may have been protected from cholera. Dark skin is protective against skin cancer, and light skin allows more vitamin D to be absorbed from the sun—a benefit if a baby lives where sunlight is scarce.

Furthermore, almost every infectious disease is more or less common because of particular alleles (McLaren et al., 2013). For example, an allele provides protection against HIV. That allele is not yet common because, unlike malaria and cholera, HIV has become widespread only in the past decades. However, many scientists are working to artificially provide exactly the chemical protection that a few people have naturally.

Until recently, after the birth of a child with a severe disorder, couples blamed witches or fate, not genes or chromosomes. That has changed, with many young adults concerned about their genes long before parenthood. Virtually everyone has a relative with a serious condition and wonders what their children will inherit. People are also curious about their own future health. Many pay for commercial genetic testing, which often provides misleading information.

Misinformation and mistaken fears are particularly destructive for psychological disorders, such as depression, schizophrenia, and autism. No doubt genes are a factor in all of these conditions (Plomin et al., 2013). Yet, as with addiction and vision, the environment is crucial for every disorder—not only what the parents do but also what the community and governments do.

This was confirmed by a study of the entire population of Denmark, where good medical records and decades of free public health allow accurate research on mental health. If both Danish parents developed schizophrenia, 27 percent of their children developed it; if one parent had it, 7 percent of their children developed it. These same statistics can be presented another way: Even if both parents developed the disease, almost three-fourths (73 percent) of their children never did (Gottesman et al., 2010). (Some of them developed other psychological disorders, again providing evidence for epigenetics.)

Even more persuasive is evidence pertaining to monozygotic twins. If one identical twin develops schizophrenia, often—but not always—the other twin also develops a psychological disorder. Obviously, genes are powerful, but also obviously, schizophrenia is not entirely genetic. Epigenetics, and prenatal and childhood experiences, are crucial.

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Numerous studies have identified environmental influences on schizophrenia, including fetal malnutrition, birth in the summer, adolescent use of psychoactive drugs, emigration in young adulthood, and family emotionality during adulthood. Because environment is crucial, few scientists advocate genetic testing for schizophrenia or any mental condition. They fear that a positive test would lead to depression and stress, factors that might cause a disorder that would not have appeared without the test. Further, a positive genetic diagnosis might add to the prejudice against people who become mentally ill (Mitchell et al., 2010).

The problems with testing for genes that cause mental disorders are only one of several complications that might emerge from a societal uptick in genetic testing. Scientists—and the general public—have many opinions about genetic testing, and nations have varying policies (Plows, 2011).

One complication is that science has revealed much more than anyone imagined a decade ago. Laws and ethics have not kept up with the possibilities, and very few prospective parents can interpret their own genetic history or laboratory results without help. Some seek abortion or sterilization without needing such a drastic step; others blithely give birth to one impaired child after another.

Professionals trained to provide genetic counseling help prospective parents understand their genetic risk so that they can make informed decisions. The genetic counselor’s task is complicated, for many reasons. One is that testing is now possible for hundreds of conditions, but it is not always accurate.

Moreover, a particular gene might increase the risk of a problem by only a tiny amount, perhaps 0.1 percent. Further, every adult is a carrier for something. It is crucial to explain test results carefully, since many people misinterpret words such as risks and probability, especially when considering personal and emotionally charged information (O’Doherty, 2006).

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Even doctors do not always understand genetics. Consider the experience of one of my students. A month before she became pregnant, Jeannette was required to have a rubella vaccination for her job. Hearing that she had had the shot, her prenatal care doctor gave her the following prognosis:

My baby would be born with many defects, his ears would not be normal, he would be intellectually disabled…. I went home and cried for hours and hours….

I finally went to see a genetic counselor. Everything was fine, thank the Lord, thank you, my beautiful baby is okay.

[Jeannette, personal communication]

It is possible that Jeannette misunderstood what she was told, but that is exactly why the doctor should not have spoken. Genetic counselors are trained to make information clear. If sensitive counseling is available, then preconception, prenatal, or even prenuptial (before marriage) testing is especially useful for:

Genetic counselors follow two ethical rules: (1) tests are confidential, beyond the reach of insurance companies and public records, and (2) decisions are made by the clients, not by the counselors.

However, these guidelines are not always easy to follow (Parker, 2012). One quandary arises when parents already have a child with a recessive disease, but tests reveal that the husband does not carry that gene. Should the counselor tell the couple that their next child will not have this disease because the husband is not the biological father of the first?

Another quandary arises when DNA is collected for one purpose—say, to assess the risk of sickle-cell disease—and analysis reveals another quite different problem, such as an extra sex chromosome or a high risk of breast cancer. This problem is new: Even a few years ago, testing was so expensive that research did not discover any conditions except those for which they were testing. Now, because of genome sequencing, many counselors learn about thousands of conditions that were not suspected and are not treatable (Kaiser, 2013). Must they inform the person? Must they tell blood relatives?

The current consensus is that information should be shared if:

But not everyone accepts that consensus. Scientists and physicians disagree about severity, certainty, and treatment. A group of experts recently advocated informing patients of any serious genetic disorder, even when the person does not want to know, and when the information might be harmful (Couzin-Frankel, 2013).

An added complication is that individuals differ in their willingness to hear bad news. What if one person wants to know, but other family members—perhaps a parent or a monozygotic twin who has the same condition—do not. We all are carriers. Do we all want to know of what?

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Sometimes couples make a decision (such as to begin or to abort a pregnancy) that reflects a mistaken calculation of the risk, at least as the professional interprets it (Parker, 2012). Even with careful counseling, people with identical genetic conditions often make opposite choices.

For instance, 108 women who already had one child with fragile X syndrome were told they had a 50 percent chance of having another such child. Most (77 percent) decided to avoid pregnancy with sterilization or excellent contraception, but some (20 percent) deliberately had another child (Raspberry & Skinner, 2011). Always the professional explains facts and probabilities; always the clients decide.

Many developmentalists stress that changes in the environment, not in the genes, are more likely to improve health. In fact, some believe that the twenty-first-century emphasis on genes is a way to avoid focusing on poverty, pollution, pesticides, and so on, even though such factors cause more health problems than genes do (Plows, 2011). Instead of genetic counseling, should we advocate health counseling?

As you have read many times in this chapter, genes are part of the human story, influencing every page, but they do not determine the plot or the final paragraph. The remaining chapters describe the rest of the story.

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