11 Gene-Environment Interactions and Genetic Conditions
Gene-Environment Interactions
Three views of gene-environment interactions that we will study are:
- Range of reaction
- Genetic environmental correlation
- Field of epigenetics (1)
Range of Reaction
Genes do not exist in a vacuum. Although we are all biological organisms, we also exist in an environment that is incredibly important in determining not only when and how our genes express themselves, but also in what combination. Each of us represents a unique interaction between our genetic makeup and our environment; range of reaction is one way to describe this interaction. Range of reaction asserts that our genes set the boundaries within which we can operate, and our environment interacts with the genes to determine where in that range we will fall. For example, if an individual’s genetic makeup predisposes her to high levels of intellectual potential and she is reared in a rich, stimulating environment, then she will be more likely to achieve her full potential than if she were raised under conditions of significant deprivation. According to the concept of range of reaction, genes set definite limits on potential, and environment determines how much of that potential is achieved.
Genetic Environmental Correlation
Another perspective on the interaction between genes and the environment is the concept of genetic environmental correlation. Stated simply, our genes influence our environment, and our environment influences the expression of our genes. Not only do our genes and environment interact, as in range of reaction, but they also influence one another bidirectionally. For example, the child of an NBA player would probably be exposed to basketball from an early age. Such exposure might allow the child to realize his or her full genetic, athletic potential. Thus, the parents’ genes, which the child shares, influence the child’s environment, and that environment, in turn, is well suited to support the child’s genetic potential. Nature and nurture work together like complex pieces of a human puzzle. The interaction of our environment and genes makes us the individuals we are.
Field of Epigenetics
In another approach to gene-environment interactions, the field of epigenetics looks beyond the genotype itself and studies how the same genotype can be expressed in different ways. In other words, researchers study how the same genotype can lead to very different phenotypes. As mentioned earlier, gene expression is often influenced by environmental context in ways that are not entirely obvious. For instance, identical twins share the same genetic information (identical twins develop from a single fertilized egg that split, so the genetic material is exactly the same in each; in contrast, fraternal twins develop from two different eggs fertilized by different sperm, so the genetic material varies as with non-twin siblings). But even with identical genes, there remains an incredible amount of variability in how gene expression can unfold over the course of each twin’s life. Sometimes, one twin will develop a disease and the other will not. In one example, Tiffany, an identical twin, died from cancer at age 7, but her twin, now 19 years old, has never had cancer. Although these individuals share an identical genotype, their phenotypes differ as a result of how that genetic information is expressed over time. The epigenetic perspective is very different from range of reaction, because here the genotype is not fixed and limited. (20)
Genetic Linkages to Behavioral Characteristics
Genes affect more than our physical characteristics. Indeed, scientists have found genetic linkages to a number of behavioral characteristics, ranging from basic personality traits to sexual orientation to spirituality. Genes are also associated with temperament and a number of psychological disorders, such as depression and schizophrenia. So while it is true that genes provide the biological blueprints for our cells, tissues, organs, and body, they also have significant impact on our experiences and our behaviors.
Let’s look at the following findings regarding schizophrenia in light of our three views of gene-environment interactions. Which view do you think best explains this evidence? In a study of people who were given up for adoption, adoptees whose biological mothers had schizophrenia and who had been raised in a disturbed family environment were much more likely to develop schizophrenia or another psychotic disorder than were any of the other groups in the study.
- Of adoptees whose biological mothers had schizophrenia (high genetic risk) and who were raised in disturbed family environments, 36.8% were likely to develop schizophrenia.
- Of adoptees whose biological mothers had schizophrenia (high genetic risk) and who were raised in healthy family environments, 5.8% were likely to develop schizophrenia.
- Of adoptees with a low genetic risk (whose mothers did not have schizophrenia) and who were raised in disturbed family environments, 5.3% were likely to develop schizophrenia.
- Of adoptees with a low genetic risk (whose mothers did not have schizophrenia) and who were raised in healthy family environments, 4.8% were likely to develop schizophrenia (Tienari et al., 2004).
The study shows that adoptees with high genetic risk were especially likely to develop schizophrenia only if they were raised in disturbed home environments. This research lends credibility to the notion that both genetic vulnerability and environmental stress are necessary for schizophrenia to develop, and that genes alone do not tell the full tale. (20)
Dig Deeper: Parental Investment and Programming of Stress Responses in Offspring
The most comprehensive study to date of variations in parental investment and epigenetic inheritance in mammals is that of the maternally transmitted responses to stress in rats. In rat pups, maternal nurturing (licking and grooming) during the first week of life is associated with long-term programming of individual differences in stress responsiveness, emotionality, cognitive performance, and reproductive behavior (Caldji et al., 1998; Francis, Diorio, Liu, & Meaney, 1999; Liu et al., 1997; Myers, Brunelli, Shair, Squire, & Hofer, 1989; Stern, 1997). In adulthood, the offspring of mothers that exhibit increased levels of pup licking and grooming over the first week of life show increased expression of the glucocorticoid receptor in the hippocampus (a brain structure associated with stress responsivity as well as learning and memory) and a lower hormonal response to stress compared with adult animals reared by low licking and grooming mothers (Francis et al., 1999; Liu et al., 1997). Moreover, rat pups that received low levels of maternal licking and grooming during the first week of life showed decreased histone acetylation and increased DNA methylation of a neuron-specific promoter of the glucocorticoid receptor gene (Weaver et al., 2004). The expression of this gene is then reduced, the number of glucocorticoid receptors in the brain is decreased, and the animals show a higher hormonal response to stress throughout their life.
The effects of maternal care on stress hormone responses and behavior in the offspring can be eliminated in adulthood by pharmacological treatment (HDAC inhibitor trichostatin A, TSA) or dietary amino acid supplementation (methyl donor L-methionine), treatments that influence histone acetylation, DNA methylation, and expression of the glucocorticoid receptor gene (Weaver et al., 2004;Weaver et al., 2005). This series of experiments shows that histone acetylation and DNA methylation of the glucocorticoid receptor gene promoter is a necessary link in the process leading to the long-term physiological and behavioral sequelae of poor maternal care. This points to a possible molecular target for treatments that may reverse or ameliorate the traces of childhood maltreatment.
Several studies have attempted to determine to what extent the findings from model animals are transferable to humans. Examination of post-mortem brain tissue from healthy human subjects found that the human equivalent of the glucocorticoid receptor gene promoter (NR3C1 exon 1F promoter) is also unique to the individual (Turner, Pelascini, Macedo, & Muller, 2008). A similar study examining newborns showed that methylation of the glucocorticoid receptor gene promoter maybe an early epigenetic marker of maternal mood and risk of increased hormonal responses to stress in infants 3 months of age (Oberlander et al., 2008).
Although further studies are required to examine the functional consequence of this DNA methylation, these findings are consistent with our studies in the neonate and adult offspring of low licking and grooming mothers that show increased DNA methylation of the promoter of the glucocorticoid receptor gene, decreased glucocorticoid receptor gene expression, and increased hormonal responses to stress (Weaver et al., 2004).
Examination of brain tissue from suicide victims found that the human glucocorticoid receptor gene promoter is also more methylated in the brains of individuals who had experienced maltreatment during childhood (McGowan et al., 2009). Examination of blood samples from adult patients with bipolar disorder, who also retrospectively reported on their experiences of childhood abuse and neglect, found that the degree of DNA methylation of the human glucocorticoid receptor gene promoter was strongly positively related to the reported experience of childhood maltreatment decades earlier. (21)
Genetic Conditions
Genetic conditions are caused in whole or in part by a change in a person’s DNA sequence. Genetic conditions can be caused by a mutation in one or multiple genes, by a combination of gene mutations and environmental factors, or by damage to chromosomes. Some genetic conditions are inherited, while others occur spontaneously. (22)
Some Genetic Disorders
Cystic Fibrosis
Cystic Fibrosis is a hereditary disease characterized by faulty digestion, breathing problems, respiratory infections from mucus buildup, and the loss of salt in sweat. The disease is caused by mutations in a single gene and is inherited as an autosomal recessive trait, meaning that an affected individual inherits two mutated copies of the gene. In the past, cystic fibrosis was almost always fatal in childhood. Today, however, patients commonly live to be 30 years or older. (23)
Down syndrome
Down syndrome is a genetic disease resulting from a chromosomal abnormality. An individual with Down syndrome inherits all or part of an extra copy of Chromosome 21. Symptoms associated with the syndrome include intellectual disability, distinctive facial characteristics, and increased risk for heart defects and digestive problems, which can range from mild to severe. The risk of having a child with Down syndrome rises with the mother’s age at the time of conception.(24)
Hemophilia
Hemophilia is an inherited disease, most commonly affecting males, that is characterized by a deficiency in blood clotting. The responsible gene is located on the X chromosome, and since males inherit only one copy of the X chromosome, if that chromosome carries the mutated gene then they will have the disease. Females have a second, usually normal, copy of the gene on their other X chromosome, so they are capable of passing on the disease without experiencing its symptoms. (25)
Tay-Sachs Disease
Tay-Sachs disease is a genetic disorder that causes progressive damage to nerve cells in the brain and spinal cord. It is caused by the absence of an enzyme called hexosaminidase-A. Without this enzyme, a fatty substance, called GM2 ganglioside, builds-up in the body, damaging cells. (26) To inherit this disease, a child must inherit a recessive gene from both parents. At birth, the newborn appears perfectly normal. Throughout the first year, the child will begin to miss developmental milestones, such as sitting up or walking. Eventually, as the GM2 ganglioside builds up in the brain and rest of the body, the child will begin to regress. A child that could once walk will become lame. A child that could once laugh becomes mute. A child that could once see becomes blind. Most children die between the ages of two to four (Cleveland Clinic Foundation, 2014). There are variations of this disease that allow for later onsets and longer lifespans; however, the type discussed here is the most common. (1)
