Chromosomal and Genetic Problems

We now focus on conditions caused by an extra chromosome or a single destructive gene. These are abnormalities in that they are not the norm (hence called ab normal). Three factors make these conditions relevant to human development:

1. They provide insight into the complexities of nature and nurture.
2. Knowing their origins helps limit their effects.
3. Information combats prejudice: Difference is not always deficit.

Not Exactly 46

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 splits to make ova, usually the split is even, 23/23. But older women are more likely to release some ova that are 22/24. Sperm also are diminished in quantity and normality with 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 (Fragiouli & Wells, 2011). Far fewer of these zygotes develop to birth (only less than 1 percent of newborns have other than 46 chromosomes) primarily because most odd-numbered organisms never duplicate, divide, differentiate, and implant.

If implantation does occur, many are aborted, spontaneously (miscarried) or by choice. Birth itself is hazardous; about 5 percent of stillborn (dead-at-birth) babies have 47 chromosomes (O. J. Miller & Therman, 2001), and many abnormal but living newborns die within the first few days. Once in about every 200 births, a newborn survives with 45, 47, or, rarely, 48 or 49 chromosomes.

Each abnormality 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 extrachromosome condition that results in a surviving child is Down syndrome, also called trisamy-21 because the person has three copies of chromosome 21.

Some 300 distinct characteristics can result from that third chromosome 21. No individual with Down syndrome is identical to another, but trisomy usually produces specific facial characteristics—a thick tongue, round face, 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).

Universal Happiness All young children delight in painting brightly colored pictures on a big canvas, but this scene is unusual for two reasons: Daniel has trisomy-21, and this photograph was taken at the only school in Chile where normal and special-needs children share classrooms.

REUTERS/CLAUDIA DAUT/LANDOV

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) (see Table 3.2). Most conceptions in which there are serious chromosomal abnormalities are aborted spontaneously.

Having an odd number of sex chromosomes impairs cognition and sexual maturation, with varied specifics depending on both genes and nurture. Sometimes only part of the 23rd pair is missing, or a person with an extra chromosome is relatively unaffected by it. In such cases, the person seems to be a normal adult but typically is infertile (Mazzocco & Ross, 2007).

Gene Disorders

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.

Dominant disorders become common only when they are latent in childhood; they appear when an adult is old enough to have had several children. 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 a person could have had several children, as did the original Mr. Huntington (Bates et al., 2002). Another exception is a rare but severe form of Alzheimer’s disease that causes dementia before age 60.

Recessive diseases are more numerous because they are passed down from one generation to the next. Some such recessive conditions are X-linked, including hemophilia, Duchenne muscular dystrophy, and fragile X syndrome, 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 inherited). Boys are much more often impaired by fragile X than girls.

Most recessive disorders are on the autosomes and thus are not X-linked (Milunsky, 2011). Carrier detection is possible for about 500 of them, a number that increases every month (Kingsmore et al., 2011). Although most recessive diseases are rare, about 1 in 12 North American men and women carries an allele for cystic fibrosis, thalassemia, or sickle-cell anemia, all equally common and devastating in children of both sexes. That high incidence occurs because carriers benefit from the gene (Brooker, 2009).

The most studied example of the benefits of recessive genes is sickle-cell anemia. Carriers of the sickle-cell gene die less often from malaria, which is still 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, who had only one copy of the gene) than it killed (those who actually had the disease because they had inherited the recessive gene from both parents). About 11 percent of Americans with African ancestors are carriers.

Similarly, cystic fibrosis is more common among Americans with ancestors from northern Europe; carriers may have been protected from cholera. Another allele provides some protection from HIV, although that allele is not yet common because, unlike malaria and cholera, HIV has become widespread only in the past decades.

Genetic Counseling and Testing

Until recently, after the birth of a child with a severe disorder, couples blamed witches or fate, not genes or chromosomes. Today, many young adults worry about their genes long before they marry. 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.

This misinformation is particularly the case 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.

For dizygotic twins and other siblings, if one develops schizophrenia, chances are that about 12 percent of their siblings also develop the disease—a risk higher than the 1 percent incidence of schizophrenia for people who have no relatives with the disease. The detailed correlations leave no doubt that genes are one factor, but that environment is also key (Castle & Morgan, 2008).

If a monozygotic twin becomes schizophrenic, often—but not always—the other identical twin also develops a psychological disorder, with the particular disorder influenced by nurture. Since even monozygotic twins differ, this means that schizophrenia is not entirely genetic.

This nature–nurture interaction was confirmed by a study of the entire population of Denmark. If both 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.

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. They fear that a positive test would itself lead to depression and stress that might be groundless, as well as more stigma for those who do develop mental illness (Mitchell et al., 2010).

Nations, scientists, and the general public have many opinions about genetic testing (Plows, 2011). The problem is that science has revealed much more about genes than anyone imagined a decade ago. Laws and ethics have not kept up with the possibilities.

Professionals trained to provide genetic counseling help prospective parents understand their genetic risk so that they can make informed decisions about their pregnancy. 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. Sometimes a particular gene increases the risk by only a tiny amount, perhaps 0.1 percent. Further, every adult is a carrier for something. It is therefore crucial to explain the results carefully, since many people misinterpret words such as risks and probability, especially when considering personal and emotional information (O’Doherty, 2006).

“The Hardest Decision I Ever Had to Make” That’s how this woman described her decision to terminate her third pregnancy when genetic testing revealed that the fetus had Down syndrome. She soon became pregnant again with a male fetus that had the normal 46 chromosomes; her two daughters also had the normal number, and so will her fourth child, not yet born when this photo was taken. Many personal factors influence such decisions. Do you think she and her husband would have made the same choice if they had no other children?

ROBERT SPENCER/THE NEW YORK TIMES/REDUX

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:

It is possible that Jeannette misunderstood what she was told, but 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:

• Individuals who have a parent, sibling, or child with a serious genetic condition
• Couples who have had several spontaneous abortions or stillbirths
• Couples who are infertile
• Couples from the same ethnic group, particularly if they are relatives
• Women over age 35 and men over age 40

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. This is no longer the case: Because of genome sequencing, many counselors will soon learn about thousands of conditions that were not suspected and are not treatable (Kaiser, 2013). Must they inform the person?

Reach for the Sky Gavin and Jake Barder both have cystic fibrosis, which would have meant early death had they been born 50 years ago. Now their parents pound on their chests twice a day to loosen phlegm—and they can enjoy jumping on the trampoline while wearing special pneumatic vests under their shirts.

ROBIN NELSON/ZUMAPRESS/NEWSCOM

The current consensus is that information should be shared if:

1. the person wants to hear it
2. the risk is severe and verified
3. an experienced counselor explains the data
4. treatment is available (Couzin-Frankel, 2011)

A group of experts recently advocated informing patients of any serious genetic disorder, whether or not the person wants to know (Couzin-Frankel, 2013). Even so, scientists and physicians disagree about severity, certainty, and treatment.

One more complication is that individuals also 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 specifics?

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.

Counseling must be individualized because each adult’s perceptions are affected by his or her partner, present and future children, work, religion, and community (McConkie-Rosell & O’Daniel, 2007). Without careful explanation and comprehension checking, misunderstanding is common. For example, half of a large group of women misinterpreted an explanation (written for the general public) about tests for genes that make breast cancer more likely (Hanoch et al., 2010).

Many developmentalists stress that changes in the environment, not in the genes, are the most promising direction for “disease prevention and more effective health maintenance” (Schwartz & Collins, 2007, p. 696). In fact, some believe that the twenty-first-century emphasis on genes is a way to avoid focus on poverty, pollution, pesticides, and so on, even though such factors cause more health problems than genes do (Plows, 2011).

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