As already explained, when a sperm and ovum create a zygote, they establish the genotype: all the genes of the developing person. That begins several complex processes that combine to form the phenotype—the person’s appearance, behavior, and brain and body functions. Nothing is totally genetic, not even such obvious traits as height or hair color, but nothing is untouched by genes, including working overtime or not at all, wanting or refusing a divorce, or becoming a devoted or a rejecting parent (Plomin et al., 2013).

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The genotype instigates body and brain formation, but the phenotype depends on many genes and on the environment. The phenotype is influenced from the moment of conception until the moment of death, sometimes directly (epigenetic) and sometime via cultural and familial circumstances.

Almost every trait is polygenic (affected by many genes) and multifactorial (influenced by many factors). A zygote might have the alleles for becoming, say, a musical genius, but that potential may never be expressed. Accurate prediction of the phenotype is impossible, even if the genotype is entirely known (Lehner, 2013).

Almost daily, researchers describe additional complexities in polygenic and multifactorial interaction. It is apparent that “phenotypic variation … results from multiple interactions among numerous genetic and environmental factors.” To describe this “fundamental problem of interrelating genotype and phenotype in complex traits” (Nadeau & Dudley, 2011, p. 1015), we begin with epigenetics.

All important human characteristics are epigenetic; this applies also to diseases that are known to be inherited, such as cancer, schizophrenia, and autism (Kundu, 2013; Plomin et al., 2013).

Type 2 diabetes is a notable example. People who inherit genes that put them at risk do not always become diabetic. However, lifestyle factors might activate that genetic risk. If that happens, epigenetic changes to the genes make diabetes irreversible: Diet and insulin may control the disease, but the pre-diabetic state never returns (Reddy & Natarajan, 2013).

One intervention—bariatric surgery to dramatically reduce weight—leads to remission of diabetes in most (72 percent) patients, but over the years full diabetes returns for more than half of them. Crucial is conscientious diet and exercise for decades; remission is possible, but the disease is latent, never disappearing because genetic changes cannot be erased (Sjöström et al., 2014).

The same may be true for other developmental changes over the life span. Drug use—cocaine, cigarettes, alcohol, and so on—may produce epigenetic changes that make addiction likely, even if a person has stopped using the drug for years (Bannon et al., 2014). Treatment and other factors help, of course, but the addict can never use the drug again as an unaffected person would.

In general, environmental influences (such as injury, temperature extremes, drug abuse, and crowding) can impede healthy development, whereas others (nourishing food, loving care, play) can facilitate it, all because of differential susceptibility and epigenetic change. A recent discovery is that some environmental factors that suppress or release genes are cognitive, not biological.

For example, if a person feels lonely and rejected, that feeling can affect the RNA, which allows genetic potential for heart disease or social anxiety to be expressed (Slavich & Cole, 2013). Note that the feeling of loneliness, not the objective number of friends or social contacts, has significant epigenetic influence.

No trait—even one with strong, proven genetic origins, such as blood pressure or severe depression—is determined by genes alone because “development is an epigenetic process that entails cascades of interactions across multiple levels of causation, from genes to environments” (Spencer et al., 2009, p. 80). Because epigenetic influences occur lifelong, latent genes can become activated at any point.

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A surprising example might be political ideology: Several researchers report that a particular allele of a dopamine receptor gene (DRD4-R7) correlates with being liberal, but only if a person has many friends. Loners, even with the liberal-leaning allele, are more conservative (Settle et al., 2010). Genotype alone does not determine phenotype for any psychological trait, but the double whammy—genes and environment—does.

Many discoveries have followed the completion of the Human Genome Project in 2001. One of the first surprises was that humans have far fewer than 100,000 genes, the number often cited in the twentieth century. A person has a total of about 20,000 genes.

The precise number is elusive because—another surprise—it is not always easy to figure out where one gene starts and another ends, or if a particular stretch of DNA is actually a gene (Rouchka & Cha, 2009). Nor is it always easy to predict exactly how the genes from one parent will interact with the genes from the other. We do, however, know some basics of genetic interaction, as described now.

Some genes and alleles are additive because their effects add up to influence the phenotype. When genes interact additively, the phenotype usually reflects the contributions of every gene that is involved. Height, hair curliness, and skin color, for instance, are usually the result of additive genes. Indeed, height is probably influenced by 180 genes, each contributing a very small amount (Enserink, 2011).

Most people have ancestors of varied height, hair curliness, skin color, and so on, so their children’s phenotype does not mirror the parents’ phenotypes (although the phenotype always reflects the genotype). I see this in my family: Our daughter Rachel is of average height, shorter than her father or me, but taller than either of our mothers. She apparently inherited some of her grandmothers’ height genes via our gametes. And none of my children have exactly my skin color—apparent when we borrow clothes from each other and are distressed that a particular shade is attractive on one but ugly on another.

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How any additive trait turns out depends partly on all the genes a child happens to inherit (half from each parent, which means one-fourth from each grandparent). Some genes amplify or dampen the effects of other genes, aided by all the other DNA and RNA (not junk!) in the zygote (Pauler et al., 2012).

Not all genes are additive. In one non-additive form, alleles interact in a dominant-recessive pattern, when one allele, the dominant gene, is more influential than the other, the recessive gene. The dominant gene controls the expression of a characteristic even when a recessive gene is the other half of a pair.

Everyone has recessive genes that are not apparent in the phenotype. For instance, no one would guess, simply by looking at me, that my mother had to stretch to reach 5’4.” But Rachel has half of her genes from me, and one of my height genes may be recessive. Every person is a carrier of recessive genes, carried on the genotype but not expressed in the phenotype.

Most recessive genes are harmless. For example, blue eyes are determined by a recessive allele and brown eyes by a dominant one, so a child conceived by a blue-eyed parent (who always has two recessive blue-eye genes) and a brown-eyed parent will usually have brown eyes. No harm in that.

“Usually have brown eyes” but not always. Sometimes a brown-eyed person is a carrier of the blue-eye gene. In that case, in a blue-eye/brown-eye couple, every child has at least one blue-eye gene (from the blue-eyed parent) and half of them will have a blue-eye recessive gene (from the brown-eyed parent). That half will have blue eyes because they have no dominant brown-eye gene. The other half will have a brown-eye dominant gene and thus have brown eyes but be carriers of the blue-eye gene, like their brown-eyed parent.

This gets tricky if both parents are carriers. Thus if two brown-eyed parents both have the blue-eye recessive gene, the chances are one in four that their child will have blue eyes (see Figure 3.3). This example is simple, because one pair of genes is the main determinant of eye color. However, as with almost every trait, eye color is polygenic, with other genes having some influence. Eyes are various shades of blue and brown, sometimes hazel, sometimes greenish.

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The crucial fact is that a recessive gene is carried, but not apparent, unless a child happens to inherit the same recessive gene from both parents. Most recessive genes are harmless (like the genes for blue eyes) but some are lethal (like those that cause serious diseases, discussed at the end of this chapter). It is important to understand the double recessive, so parents do not blame each other when their child has a recessive disease, and husbands do not suspect infidelity if his child is unexpectedly blue-eyed or red-haired.

A special case of the dominant–recessive pattern occurs with genes that are X–linked (located on the X chromosome). If an X-linked gene is recessive—as are the genes for most forms of color blindness, many allergies, several diseases, and some learning disabilities—the fact that it is on the X chromosome is critical in determining whether it will be expressed in the phenotype (see Table 3.1). Boys will have the trait; girls will usually be carriers.

To understand this, remember that the Y chromosome is much smaller than the X, containing far fewer genes. For that reason, genes on the X almost never have a match on the Y. Therefore, recessive traits carried on the X have no dominant gene on the Y.

A boy, XY, with a recessive gene on his X, has no gene on his Y to counteract it, so his phenotype is affected. A girl will be affected only if she has the recessive trait on both her X chromosomes, which is rare. This explains why males with an X-linked disorder inherited it from their mothers, not their fathers. Because of their mothers, 20 times more men than women are color-blind (McIntyre, 2002).

For any living creature, the outcomes of all the interactions involved in heredity are difficult to predict. A small deletion, repetition, or transposition in any of the 3 billion base pairs may be inconsequential, deadly, or something in between.

When the human genome was first mapped in 2001, it was hoped that a specific additive, recessive, or dominant gene could be located for each genetic disorder. Then a cure would soon follow. That “one gene/one disorder” expectation proved to be fantasy, disappointing many doctors who hoped that personalized medicine was imminent (Marshall, 2011). Molecular analysis found, instead, that thousands of seemingly minor variations in base pairs turn out to be influential—each in small ways. Since there are 3 billion base pairs, all the small variations can add up to have a notable impact.

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Attention has focused on copy number variations, which are genes with repeats (from one to hundreds) or deletions of base pairs. Copy number variations correlate with almost every disease and condition, including heart disease, impaired intellectual abilities, mental illness, and many cancers.

We all have copy number variations: There is no person who is completely normal, genetically. One team, looking specifically at genes for neurons in the brain, says “dysfunctions abound … with a large number of functional variants in every genome” (Macosko & McCarroll, 2013, p. 564).

Researchers are just beginning to understand the implications of copy number variations, although many hope that soon such genetic information will help target drugs and other medical measures, such as which cocktail of chemotherapy will stop which cancer. Even that may be a hopeful fantasy. Since epigenetics shows that environmental influences can actually change genetic expression, personalized medicine must consider each individual’s habits of mind and life at least as much as their genes (Horwitz et al., 2013).

To further complicate matters, sometimes one-half of a gene pair switches off completely, allowing the other free rein but potentially causing a problem if that remaining gene has a deleterious variation, recessive or not. For girls, one X of the 23rd pair is deactivated early in prenatal life. The implications of that shut-off are not well understood, but it is known that sometimes that X is from the ovum, sometimes from the sperm. Boys, of course, have only one X, so it always is activated.

X deactivation in girls but not boys is not the only case that is affected by a person’s sex. Sometimes the same allele affects male and female embryos differently. It also matters whether a gene came from the mother or the father, a phenomenon called parental imprinting.

The best-known example of parental imprinting occurs with a small deletion on chromosome 15. If that deletion came from the father’s chromosome 15, the child may develop Prader-Willi syndrome and be obese, slow-moving, and stubborn. If that deletion came from the mother’s chromosome 15, the child will have Angelman syndrome and be thin, hyperactive, and happy—sometimes too happy, laughing when no one else does. In both cases, intellectual development is impaired, though in somewhat distinct ways.

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Parental imprinting is quite common. Early in prenatal development (day 15), an estimated 553 genes act differently depending on whether they come from the mother or from the father—a much higher number than previously thought (Gregg, 2010). Imprinting may be affected by the sex of the embryo as well as the sex of the parent. For instance, women develop multiple sclerosis more often than men, and they usually inherit it from their mothers, not their fathers, probably for genetic as well as epigenetic reasons (Huynh & Casaccia, 2013).