Human Genetics: The Basics

Ricki Lewis

• Publisher: Garland Science
• Year: 2016
• ISBN:
  9781315406961
• Edition: 2
• Topic: Scienze biologiche
• Subtopic: Genetica e genomica

Human genetics has blossomed from an obscure biological science and explanation for rare disorders to a field that is profoundly altering health care for everyone. This thoroughly updated new edition of Human Genetics: The Basics provides a concise background of gene structure and function through the lens of real examples, from families living with inherited diseases to population-wide efforts in which millions of average people are learning about their genetic selves. The book raises compelling issues concerning:

• The role of genes in maintaining health and explaining sickness

• Genetic testing, gene therapy, and genome editing

• The common ancestry of all humanity and how we are affecting our future.

Written in an engaging, narrative manner, this concise introduction is an ideal starting point for anyone who wants to know more about genes, DNA, genomes, and the genetic ties that bind us all.

1

FROM MENDEL’S PEAS TO DOUBLE HELICES

The Rosetta Stone is an ancient Egyptian artifact that made it possible to glean meaning from hieroglyphic writings. The content of the etchings on the stone tablet proved not as memorable as the connections of the symbols to each other. The stone, a statement from Ptolemy V set down in 196 BC, held instructions to erect statues in temples and spelled out a particular tax repeal—news of the day, more or less. But the tablet depicted the messages in three languages— two Egyptian and classical Greek. The lasting knowledge was to come in the comparison of the three languages, and in the ability to go from one to another.

FROM GENES TO GENOMES

Like the Rosetta Stone, the human genome is a set of instructions, also for building a temple of sorts—a human body. Two copies of our genome are tightly entwined inside each of our cells, which are the microscopic building blocks of our bodies. The three languages of the genome are the informational molecules DNA, RNA, and protein, presented in Figure 1.1 and Table 2.2. A gene is the information in a sequence of DNA building blocks that is transcribed (copied) into a molecule of RNA, which is translated into (used to build) a protein. The protein is responsible for, or contributes to, the trait or illness associated with the gene. Although only about 1.5 percent of the 3.2 billion bases of a human genome encodes proteins, these DNA sequences are very important—abnormal or absent specific proteins account for about 85 percent of inherited diseases. The protein-encoding part of the genome is called the exome. If the genome is compared to the Internet in terms of amount of information, then the exome is a little like accessing only a tiny part of that information.

Figure 1.1 From DNA to RNA to protein.

Source: Molecular Biology of the Cell, 6th edition, Figure 1–4, p. 4

A cell can transcribe a gene’s worth of DNA sequence information into RNA, and then translate the RNA into a specific sequence of protein building blocks, the amino acids. These two processes are appropriately called transcription and translation. Proteins provide basic characteristics, such as the ability of blood to clot or for the body to extract energy from foods, as well as contribute to harder-to-define qualities such as talents and personality.

The DNA sequence of a particular gene can vary slightly from person to person. Most gene variants have no effect on characteristics, including health, like the meaning of a written sentence being clear even if it contains one or two typos. Just as a more serious keying error, such as removing words or changing an important letter—bloke to broke, for example—can greatly alter the meaning of a sentence, some changes in a gene’s DNA sequence can harm health. These types of variants are traditionally termed mutations.

Different types of cells under different circumstances transcribe and translate different sets of genes. A fat-stuffed adipose cell, which stores energy, utilizes a very different gene set than a long, lean muscle cell, which expends energy to fuel contraction. The gene expression (activation) patterns of these two cell types—which gene sets they transcribe—would differ between a well-fed athlete and a person who is starving.

A human genome is also like the Rosetta Stone in that the bigger genetic picture may be more valuable than the many individual bits of information it contains. A genome-wide view of ourselves reveals that our DNA sequences are 99 percent alike, uniting humanity. Yet within that other less than 1 percent of our DNA sequences lie the intriguing differences that are responsible for our individuality and our illnesses.

The six chapters of this book explain what genes are, how they provide instructions for the functioning of the human body, and how they can reveal our past. Chapter 1 traces the history of the science of genetics, from thoughts on family resemblances to discovery of the underlying laws of inheritance, to cracking the genetic code and sequencing and deciphering human genomes. Chapter 2 paints the landscape of genetics from the DNA level to the population level through the example of a disease, cystic fibrosis. Chapter 3 explores how considering genes is making the practice of medicine both more precise and more personal, focusing on cardiovascular disease, cancer, and infectious disease. Genetic testing teamed with information science has shrunk times to diagnosis from years to minutes. It is the subject of Chapter 4. Adding, removing, or replacing genes is covered in Chapter 5. Finally, Chapter 6 is both a look back into our past and glimpses of our future, courtesy of our DNA. The “What Would You Do?” feature ending each chapter presents dilemmas that arise from genetic research, information, applications, and technologies.

AGRICULTURE IS APPLIED GENETICS

Today, primary school students are familiar with the structure and function of DNA. However, the rules of inheritance were deduced over many years, from experiments based on observations of trait variations. It wasn’t until 1865 that “the monk in the garden” Gregor Mendel carried out his famous experiments on pea plants that revealed the two basic laws of heredity, and decades before his contribution was acknowledged. However, the science of genetics actually began millennia earlier, when people learned how to control the reproduction of the species they needed to survive.

Agriculture provided the numbers from which researchers eventually deduced the laws of inheritance. The controlled breeding that is the backbone of farming, with its intense selection of coveted traits and removal of undesirable ones, is actually a huge genetic experiment.

From 15,000 to 8,000 years ago, agriculture arose independently in different parts of the world. The time of its origin in different places depended upon climate, geography, the movements of people who “hunted and gathered,” and their growing ability to control their environment. Agriculture grew out of astute observations. Imagine a group of nomads settling overnight in an area with edible plants. They ate, perhaps took food with them when they left, and inadvertently left seeds behind from tasty fruits and grains. A year later, the people returned and noted the same types of plants growing. At some point, someone must have observed a seedling sprouting a tiny stem and linked the seeds of one season to the bounty of the next. Then, people began leaving seeds on purpose, saving the seeds from the most robust plants each season to plant the crops the next year. Domestication of wild animals such as sheep and goats paralleled the control over plant breeding. Eventually, people must have realized that if they could grow crops, they needn’t move to find food. Settlements eased living and provided some safety.

The first farmers were insightful observers of natural variation. Consider the origin of corn, also known as maize and Zea mays, in southern Mexico about 9,000 years ago. People began, unknowingly at first, fashioning the seeds of a wild grass that still grows there, called teosinte, into corn.

Corn and its ancestor, teosinte, do not look much alike. In contrast to a corn plant’s majestic height, with its seeds tucked into paired protective husks and its stalk firm enough to withstand a strong wind, teosinte is stout and branched, each outgrowth holding a small, ragged ear. Corn kernels are packed with protein, oil, and starch, in a soft covering that teeth can easily tear. In contrast, teosinte kernels are small, trapped in a hard fruitcase, and form two scraggly rows in a puny cob. A corn husk hugs the succulent kernels in their neat rows; pebble-like teosinte seeds simply drop and scatter. Teosinte’s tough seeds, though, traverse an animal’s digestive tract unscathed, plopping from the anus into hopefully fertile ground, where they start a new plant.

Corn could not have evolved naturally, because its seeds would never have survived the journey through the digestive tracts of herbivores. So how has corn, with its shrouded seeds, persisted? We helped it.

Archeological evidence indicates that people once grated teosinte seeds into flour. In doing so, someone must have come upon an unusual plant that had larger or softer kernels. Perhaps from knowing how to cultivate other crops from early agriculture in Mexico—yams, squash, cotton, peanuts, and peppers—the people knew to save the seed and plant it to propagate the desirable traits. Over time, with continual selection at each generation for the most palatable and digestible kernels, teosinte became corn. However, in the process, the new crop sacrificed its self-sufficiency, because people would always have to remove the kernels from the husks and plant them.

Selecting seeds to perpetuate a valued trait is recognition of genetics. Today, we know that the differences between corn and teosinte are due to the actions of only a few genes. One, called tb1, controls body form—the gene variant in teosinte confers the shrublike shape, whereas the variant in corn suppresses an ancestral tendency to grow laterally, resulting in the cornstalk. Another gene controls the pattern of deposition of silica (the main component of sand) and lignin (a carbohydrate) in the kernels, which underlies the differences in hardness between the seeds of corn and teosinte.

Comparing differences in gene sequences among modern cultivars of corn and teosinte and considering mutation rates and geographical distribution suggest a single origin for corn about 9,000 years ago, in southern Mexico. Consistent with the DNA story are preserved ears that track the changes that accompanied corn’s human-aided evolution from teosinte. Once corn had been cultivated, it rapidly replaced its forebear. Evidence of tools to process corn date from 8,700 years ago—tiny crevices in the tools bore starch characteristic of modern corn, but not of teosinte.

Agriculture began in different parts of the world within a few thousand years and transformed humanity. The hunter-gatherer lifestyle gave way to settlements, and people came to rely on fewer varieties of foods as crops abounded. So, too, were the seeds sowed for the birth of the field of genetics.

MENDEL’S EXPERIMENTS—THE MYSTERY OF THE MISSING TRAITS

The two basic laws of inheritance emerged from a mystery in gardens and farms: traits that vanish and then reappear. Specifically, crossing plants where each has a different version of a trait—flower color, for example—produces hybrids with flowers of only one of the colors. Cross the hybrids, or allow them to self-fertilize, and, in the next generation, both flower colors appear. How does a trait disappear in the hybrid generation, and then reappear when the hybrids are crossed or selfed? Gregor Mendel (1822–1884) used math to unmask the hidden traits.

MENDEL THE MAN

Johann Mendel was born in 1822 to parents who were serfs, in a tiny village in northern Moravia. Johann became “Gregor” in 1843, and Moravia became Czechoslovakia in 1945. Mendel was a good student, but attended university only briefly before entering the monastery of the Augustinian Friars at Saint Thomas in Brunn (now Brno), where he studied theology, history, Greek, law, and teaching. After being ordained in 1847, Mendel taught math and Greek at a local school, but failed his teacher certification exam because he couldn’t classify mammals. For a short time, as a parish priest, he visited hospitalized patients, but became so squeamish, in those days before anesthesia, that he quickly ruled out a career in medicine.

Despite his ineptitude at classifying mammals, Mendel proved himself a gifted teacher, and the monks sen...