This brief reminder chapter aims to freshen up what professionals in reproduction may have learned a while ago at university, and will also serve the reader as a source of information to comprehend the following, more complex chapters. At the end of this chapter, basic study books or broad reviews are recommended for further reading rather than regular scientific references, to help the reader in the further understanding of this textbook.

Infertility is a genetically heterogeneous condition affecting about 10% of women of reproductive age. Genetic studies on animal models have identified thousands of candidate genes that are essential for gonadal development, germline cell differentiation, complex oocyte–granulosa intercellular signaling, gametogenesis, fertilization, and fetal development. A subset of these candidate genes derived from animal models has been found to cause ovarian dysfunction and infertility in humans.

The World Health Organization (WHO) defines infertility as the inability to conceive within 12 months despite regular unprotected intercourse, a condition that concerns about 10–15% of couples globally. Infertility is considered as primary or secondary depending on whether a couple has experienced a prior pregnancy or not.

Preimplantation genetic testing (PGT) allows the detection of genetic abnormalities in biopsies that comprise 1–10 cells from preimplantation embryos and is performed to avoid the transmission of inherited and de novo genetic abnormalities to the offspring (Figure 2.1) (see Chapter 13). The minute amount of genomic DNA in a single cell represented a challenge for whole-genome profiling of embryo biopsies on development of PGT in the 1990s because whole-genome analysis technologies required micrograms of input DNA. Before the adaptation of these technologies to single-cell input by whole-genome amplification (WGA) methods, PGT was performed using targeted approaches according to the couple’s indication [1] (Table 2.1). For instance, fluorescence in situ hybridization (FISH) was used to detect unbalanced karyotypes in the embryos from balanced translocation carriers or from couples with recurrent miscarriage or implantation failure. In case of Mendelian disorders, embryo biopsies were subjected to multiplex polymerase chain reaction (PCR) of the risk allele(s) together with several cosegregating polymorphic markers. These targeted approaches were developed for each family specifically, rendering them labor-intensive, costly, and time-consuming. Moreover, some mutations (e.g. a priori unknown small deletions and duplications or complex chromosomal rearrangements) were practically impossible to diagnose using these strategies. The development of WGA technologies in the early 2000s, their application in genomic array technologies thereafter, and the decrease in cost of next generation sequencing (NGS) helped to overcome these limitations and enabled whole-genome profiling of single cells. Furthermore, the improvements in embryo culture made trophectoderm (TE) biopsy possible at the blastocyst stage, enabling 5–10 cells to be biopsied and tested. Besides increasing the diagnostic accuracy, this allowed for the detection of the mosaic status of genetic variants genome-wide [1]. In parallel, the advancement of embryo cryopreservation techniques expanded the time frame required for embryo diagnosis and therefore also contributed to the development and application of new PGT technologies and data analysis.

Since the birth of the first baby via in vitro fertilization (IVF) in 1978, there has been concern about the safety of IVF and other assisted reproduction technology (ART) procedures for the health of ART-conceived children. Data show that ART singletons are at increased risk for adverse perinatal outcomes such as low birthweight and being small for gestational age, and congenital malformations [1]. The biological mechanism behind these risks is mainly unresolved. Since the publication of a few case reports on the incidence of rare imprinting disorders such as Angelman and Beckwith–Wiedemann syndromes in ART-conceived children, epigenetic deregulation has gained increasing attention as a possible common cause for the adverse outcomes. This led to an expansion of ART literature on epigenetic effects. In this chapter, I focus on the current knowledge of epigenetic disturbances in humans, reported after ART in general and in relation to specific ART components, and the difficulties encountered in these kinds of studies. When needed, animal studies will also be mentioned. The subfertility of the population as a possible cause for the epigenetic deregulation is also taken into consideration. Finally, I discuss whether epigenetic effects can be related to the reported health outcome in ART children and if these possible derangements can affect their health at adult age.

The Human Genome Project officially began in the USA in October 1990 under the auspices of the Department of Energy and the National Institutes of Health (NIH) under the direction of Francis Collins. The objective was to build genetic and physical maps of the entire human genome, and at the same time to develop the technology needed to perform DNA sequencing on a large scale. Extensive international collaboration and advances in the field of genomics and bioinformatics enabled the first essentially complete version of the human genome (92.3% of the total) to be officially announced 13 years later, two years ahead of schedule, on April 14, 2003, with 99.9% reliability.

To understand heredity–behavior relations it is important to first understand the mechanisms of heredity. The gains in knowledge about genetics in the twentieth century are stunning. An obscure scientific paper that was published in the late nineteenth century and rediscovered at the beginning of the twentieth laid the foundation for identifying the molecule of heredity about fifty years later, and for the project to map all human genes about fifty years after that. Basic principles of genetics are taught in middle schools today and it is generally accepted that genetic variation plays a role in individual differences in behavior. In this chapter we discuss some ideas about heredity that predate our modern understanding. We also examine the life of two important figures in the history of genetics and describe their contributions.

Have you ever drunk more alcohol than you intended? Or smoked a cigarette after telling yourself that you were quitting smoking? Have you ever gotten a headache because you did not drink your morning coffee? By the time we are adults, nearly all of us have used substances such as alcohol, tobacco, or caffeine. Most of us can control our use of substances, but a sizeable minority develop one or more disorders due to substance use at some point in their lives. You probably know someone who has problems that are a result of substance use.

The first six chapters of this book introduced you to behavior genetics as a field, refreshed your memory about Mendelian and molecular genetics, introduced the research methods of behavior genetics, and discussed how genetic variation can affect the brain structure and function. In the remaining chapters, we explore some of the most important areas of behavior genetic research, consider the future of behavior genetics, and examine ethical questions at the forefront of behavior genetics.

Behavior genetics – the scientific study of heredity–behavior relations – has come of age. Since the middle of the twentieth century, accumulating scientific evidence has shown that genetic differences between individuals play a significant role in behavioral differences between them. In fact, it is now generally accepted that genetic variation is an important contributor to individual differences in behavior. Although the fundamental question about the role of inheritance in behavioral resemblance is not new, recent technological advances provide new ways to peek behind nature’s curtain. It is easy to get excited about the potential for discoveries in behavior genetics. We appear to be entering a new era in which it may be possible to understand the biological mechanisms responsible for familial behavioral resemblance. However, we should enter this era with humility. The history of behavior genetics is full of periods of excitement followed by disappointment. It also contains sobering lessons of scientific hubris and state-sponsored human rights violations. There is a lot to be excited about, but it is important to remember history, and to understand the limitations of behavior genetics, especially when considering the application of behavior genetic findings to human beings.