One important, and for some the most surprising, conclusion of genome-wide association studies (GWAS) has been that in most cases numerous single nucleotide polymorphism (SNPs) in several genes were found to be associated with the development of a characteristic or the risk of developing a disease. As already mentioned, the main conclusion has been that the relationship between genes and characteristics or diseases is usually a many-to-many one, as many genes may be implicated in the same condition, and the same gene may be implicated in several different conditions. In fact, the same allele may be protective for one disease but increase the risk for another. For example, a variation in the PTPN22 (protein tyrosine phosphatase, nonreceptor type 22) gene on chromosome 1 seems to protect against Crohn’s disease but to predispose to autoimmune diseases. In other cases, certain variants are associated with more than one disease, such as the JAZF1 (JAZF1 zinc finger 1) gene on chromosome 7 that is implicated in prostate cancer and in type 2 diabetes. Therefore, we should forget the simple scheme of gene 1 → condition 1/gene 2 → condition 2, and adopt a richer – and certainly more complicated – representation of the relationship between genes and disease. Additional GWAS on more variants in larger populations might provide a better picture in the future. But insofar as we do not understand all biological processes in detail, all we are left with are probabilistic associations between genes and characteristics (or diseases). The “associated gene” may be informative, but its explanatory potential and clinical value are limited – at least for now.

Common misunderstandings about evolution and responses stemming from this book

This chapter is about the public image of genes. But what exactly do we mean by “public”? Here, I use the word as a noun or an adjective vaguely, in order to refer to all ordinary people who are not experts in genetics. I thus contrast them with scientists who are experts in genetics – that is, who have mastered genetics-related knowledge and skills, who practice these as their main occupation, and who have valid genetics-related credentials, confirmed experience, and affirmation by their peers. I must note that both “experts” and “the public” are complex categories that depend on the context and that change over time. There is no single group of nonexperts that we can define as “the” public, as people around the world differ in their perceptions of science, depending on their cultural contexts. We had therefore better refer to “publics.” The differences among experts nowadays might be less significant than those among nonexperts, given today’s global scientific communities, but they do exist. Finally, both the categories of experts and publics have changed across time, depending, on the one hand, on the level of experts’ knowledge and understanding of the natural world, and, on the other hand, on publics’ attitudes toward that knowledge and understanding.

If you were taught Mendelian genetics at school (see Figures 2.1 and 2.2) you should be aware that it is an oversimplified model that does not work for most cases of inherited characteristics. Human eye color is a textbook example of a monogenic characteristic. It refers to the color of the iris – the colored circle in the middle of the eye. The iris comprises two tissue layers, an inner one called the iris pigment epithelium and an outer one called the anterior iridial stroma. It is the density and cellular composition of the latter that mostly affects the color of the iris. The melanocyte cells of the anterior iridial stroma store melanin in organelles called melanosomes. White light entering the iris can absorb or reflect a spectrum of wavelengths, giving rise to the three common iris colors (blue, green–hazel, and brown) and their variations. Blue eyes contain minimal pigment levels and melanosome numbers; green–hazel eyes have moderate pigment levels and melanosome numbers; and brown eyes are the result of high melanin levels and melanosome numbers. Textbook accounts often explain that a dominant allele B is responsible for brown color, whereas a recessive allele b is responsible for blue color (Figure 4.1). According to such accounts, parents with brown eyes can have children with blue eyes, but it is not possible for parents with blue eyes to have children with brown eyes. This pattern of inheritance was first described at the beginning of the twentieth century and it is still taught in schools, although it became almost immediately evident that there were exceptions, such as that two parents with blue eyes could have offspring with brown or dark hazel eyes.

In the preface of the present book I mentioned the 1997 film GATTACA. What was science fiction then is nowadays represented as a possibility. Private companies seem to offer GATTACA-type genetic tests to parents, with the promise to assess embryos for a variety of conditions. Despite the limitations of polygenic risk scores (PRSs), briefly discussed in the previous chapter, according to the company Genomic Prediction, they can be used to assess disease risk. To achieve this, couples have to undergo the procedures of in vitro fertilization. Each woman receives hormones to stimulate ovulation, and ova are selected and fertilized with their husband’s sperm. Then, after a few days, embryos consisting of a handful of cells undergo preimplantation genetic diagnosis. This is a process during which a single cell of the developing embryo is removed and tested for the presence of DNA variants related to a condition. On the basis of this, PRSs for each embryo can be calculated and decisions can be made about which embryo(s) should be transferred to the mother’s uterus for implantation. Currently, the company is quite clear on their website about what can and cannot be done.

Perhaps you were taught at school that genetics began with Gregor Mendel. Because of his experiments with peas, Mendel is considered to be a pioneer of genetics and the person who discovered the laws of heredity. According to the model of “Mendelian inheritance,” things are rather simple and straightforward with inherited characteristics. Some alleles are dominant – that is, they impose their effects on other alleles that are recessive. An individual who carries two recessive alleles exhibits the respective “recessive” characteristic, whereas a single dominant allele is sufficient for the “dominant” version of the characteristic to appear. In this sense, particular genes determine particular characteristics (e.g., seed color in peas), and particular alleles of those genes determine particular versions of the respective characteristics. Mendel, the story goes, discovered that characteristics are controlled by hereditary factors, the inheritance of which follows two laws: the law of segregation and the law of independent assortment.