#57. A Summary of ‘Inheritance: How Our Genes Change Our Lives–and Our Lives Change Our Genes’ by Sharon Moalem

inheritance_sharon_moalem

‘Inheritance: How Genes Change Our Lives–and Our Lives Change Our Genes’ by Sharon Moalem (Grand Central Publishing; April 15, 2014)

Table of Contents:

i. Introduction/Synopsis

PART I: HOW OUR GENES CHANGE OUR LIVES

Section A. Basic Genetics

1. Basic (Mendelian) Genetics

2. Congenital Insensitivity to Pain

3. Genetic Detective Work

Section B. Genes and Diet: Genetic Disorders of Metabolism

4. Trouble with Dairy: Lactose Intolerance

5. Trouble with Fruit: Hereditary Fructose Intolerance

6. Trouble with Protein (Part I): Phenylketonuria

7. Trouble with Protein (Part II): Ornithine Transcarbamylase Deficiency

8. How We’re All Different When It Comes to Our Genetic Metabolism

Section C. Genes and Drugs

9. Pharmaceuticals Gone Wrong

PART II: EPIGENTICS: HOW OUR LIVES CHANGE OUR GENES

Section D. Epigenetics and Development

10. Fetal Development

11. Fetal Alcohol Syndrome

12. Sexual Development

Section E. Epigenetics and Environmental Triggers

13. Epigenetics and Bones

14. From the Depths of a Hangover, to the Tip of Mount Everest

  • 14a. Genes and Hangovers
  • 14b. Epigenetics and EPO
  • 14c. Genes and Sherpas

15. Epigenetic Inheritance

  • 15a. Diet & Obesity and Epigenetic Inheritance
  • 15b. Stress and Epigenetic Inheritance

16. The Hope of Epigenetic Drugs, Treatments, and Therapies

17. Conclusion

i. Introduction/Synopsis

The task of reading a full human genome—with all its 3 billion base pairs—was first accomplished back at the turn of the century, through the monumental enterprise known as the Human Genome Project (HGP). In terms of the brass tacks, the HGP itself took over a decade, and cost nearly $3 billion dollars. Since that time, advances in technology have made gene sequencing vastly cheaper and less time consuming (reading a genome now takes less than a day, and costs less than $1,000). As a result, gene sequencing has become very commonplace, and thus the amount of data we have regarding our genome has grown enormously. Still, while the HGP was an incredible accomplishment, and the advances we have made since then are nothing short of remarkable, the secrets behind DNA have not been unlocked nearly as quickly as we might have hoped, or expected.

The main reason for this is that the more we discover about DNA, the more we discover just how complicated this molecule truly is. For one thing, as many of us now know, it is not the case that single genes code neatly for individual traits. Most traits are influenced by multiple genes (if not hundreds), and figuring out just what genes are involved, and in what ways, is often extremely difficult.

As if this were not already enough, scientists have also found that genes are capable of being turned on and off—and also up and down. In terms of the mechanics involved, some of these switches are flipped by other genes, in the normal course of development, while others are flipped by environmental triggers, and can change from moment to moment. What this means is that figuring out how genetics works does not just depend on knowing what genes are present, but how these genes express themselves (or fail to express themselves) at different times. The study of how and why genes express themselves differently at different times is known as epigenetics, and it adds a whole other layer of complexity to an already very complex affair.

That’s not all, though. Geneticists have also found that some of the genetic switches that are flipped by environmental triggers are capable of persisting for years—and even being passed down from one generation to the next. Thus genetic inheritance is not a simple matter of the genes themselves—as was once thought—but how these genes are tuned by the environment.

Still, unraveling all this complexity is not entirely without hope. Scientists have a number of tools at their disposal, and progress has been made in at least some areas.

One of the greatest tools that scientists have at their disposal in unraveling the genetic mystery is the study of people with rare genetic disorders. These cases are particularly revealing because they are often caused by just one or a few genes, and looking at the entire genomes of these individuals often reveal just where the problem is.

Unfortunately, treating rare genetic disorders is not always as easy as spotting what’s wrong. Nevertheless, geneticists have made headway with at least some of these disorders. Take Sharon Moalem, for example. Moalem has been working with individuals with rare genetic disorders his entire career; and in this time he has learned an enormous amount both about genetics, and about how he can use this knowledge to help his patients. One great ray of hope comes from the fact that genes can be influenced by environmental factors (as we have seen above), and thus the right environment (including diet and pharmaceuticals) can often be used to help those afflicted.

And while Moalem has used his findings to help his patients, the rare cases themselves also help shed light on the field of genetics more broadly—which not only advances the field, but also holds the promise of helping many more people in the future.

Here is a trailer for the book:

What follows is a full executive summary of Sharon Moalem’s Inheritance: How Our Genes Change Our Lives—and Our Lives Change Our Genes.

PART I: HOW OUR GENES CHANGE OUR LIVES

Section A. Basic Genetics

1. Basic (Mendelian) Genetics

The most basic understanding of genetics is that genes translate neatly and straightforwardly into physiological traits—such as “eye color, curly hair, tongue rolling, or hairy fingers [etc.]” (loc. 26). In terms of the specifics, each of us is equipped with a double set of genes, one from our mother and one from our father—though only 1 of the 2 pairings of each gene is expressed in each of us (loc. 431). When it comes to determining which gene is expressed in each case, this has to do with whether the genes themselves are dominant or recessive (loc. 431).

All of these basic laws of genetics were worked out over a century ago by the famous Augustinian monk Gregor Mendel (even before the actual genes themselves were discovered), from experiments that Mendel performed with pea plants (loc. 429-41). Admittedly, our understanding of genetics has grown enormously since the time of Mendel. However, sometimes things are in fact as simple as Mendel had discovered them to be with his famous peas. And this is as true with run of the mill traits as it is with genetic diseases. Let’s take a look at our first example.

2. Congenital Insensitivity to Pain

One very remarkable genetic disorder caused by but a single gene is congenital insensitivity to pain. As the name would suggest, this disorder causes the ‘sufferer’ to feel no pain. The gene responsible is one called SCN9A, which, under normal circumstances, codes for a protein that functions to help pass the pain signal from one cell to the next all the way up to the brain (loc. 2116). A small mutation on this gene prevents the protein from doing its job, thus causing the condition. As Moalem explains, “the difference between people who are insensitive to pain and others on this planet is just a small variation in the version of the SCN9A gene that we’ve inherited… [that] result[s] from nonfunctioning gates that sit on the surface of our cells and mediate, or determine, what goes in and what comes out. In the case of some people who feel no pain, the protein that is made from the SCN9A gene stops the signal from being sent. The message is dropped off, but instead of setting forth on a swift and wild adventure, the pony and its rider just dawdle at the corral” (loc. 2116).

The story of how the gene responsible for congenital insensitivity to pain was discovered is almost as remarkable as the disorder itself. The story takes us to Lahore, Pakistan, where a boy (left unnamed in the book) lived with the condition. The boy had made a name (and a living) for himself by demonstrating his imperviousness to pain. As the author explains, “as a human pincushion, he made a living from his apparent inability to feel pain in street performances, impaling himself with all sorts of sharp objects (none of them sterile), swallowing swords, walking on hot coals, and expressing not the slightest hint of being bothered by it all” (loc. 2120).

A team of scientists from the Cambridge Institute for Medical Research eventually heard of the boy, and decided to head to Lahore to investigate. Unfortunately, by the time they arrived, the boy had managed to kill himself performing one of his feats. As Moalem explains, “by the time the scientists reached Lahore, tragically, the boy was dead, just shy of his fourteenth birthday, having jumped off a building in an attempt to impress his friends” (loc. 2120).

Still, the scientists were able to take a blood sample from the boy to investigate his DNA. Actually, as it turned out, several other members of the boy’s family also claimed to have the same condition, so the scientists looked at all of their DNA—and it soon became clear just where the condition was coming from. As the author explains, “interviews with relatives in the boy’s extended family revealed several others who reported that they’d never felt pain, and a dive into their genetic pool showed that all of them had one thing in common: the same mutation in their SCN9A gene” (loc. 2124).

3. Genetic Detective Work

Just how did the scientists manage to locate the rogue gene? Fairly simply, in fact. It was just a matter of looking at the genomes of the afflicted parties, and comparing them against the genomes of masses of other people (that do not have the disorder) to see where the crucial divergence lay (loc. 2810).

Of course, genetic disorders do not always come down to a defect in a single gene, but sometimes they do, and in these cases it’s particularly easy to discern what’s going on (loc. 2136). In fact, monogenic traits and disorders are so simple to decipher—and discerning traits and disorders caused by multiple genes is so much more difficult—that the bulk of the progress we’ve made in understanding which genes are responsible for which traits and disorders has indeed come from traits and disorders that are the consequence of single genes. As the author explains, “since the human genome was first published, the rush was on to identify genes linked with specific traits—and most of the low-hanging fruit was picked clean pretty quickly. Many of the gene-linked conditions we’ve identified thus far are monogenic. As in the boy from Lahore who didn’t feel pain, these changes can result from alterations in one single gene. Far trickier is the task of untangling the complicated web of factors that give rise to conditions such as diabetes and hypertension that likely involve more than one gene” (loc. 2136).

As mentioned in the quote, the genetic analysis described above was not even possible until about a decade ago. It was only then that reading the full genomes of individuals became technically feasible. Since then the technology used to read genomes has advanced in leaps and bounds, and thus by now we have built up a substantial data base of human genetic material. As Moalem explains, “it wasn’t so long ago that no one—not even the richest person in the world—could get a peek into their genome. The science simply wasn’t there. Today, though, the cost of exome or whole genome sequencing, an invaluable genetic snapshot of the millions of nucleotide ‘letters’ that make up our DNA, is less than the cost of a high-quality wide-screen TV. And it’s getting cheaper by the day. A veritable flood of never-before-seen genetic data has arrived” (loc. 166).

Despite the fact that we now have a flood of genetic data, this does not meant that the secrets of DNA have been unlocked as fast as the data itself has grown. As mentioned above, traits and conditions that are the consequence of multiple genes are notoriously difficult to decipher—even with the growing body of genetic data we have access to. Before we launch into DNA’s incredible complexity, however, it is worth it to remain for a while at the level of the very simple—with conditions that are caused by defects in single genes.

*For prospective buyers: To get a good indication of how this (and other) articles look before purchasing, I’ve made several of my past articles available for free. Each of my articles follows the same form and is similar in length (15-20 pages). The free articles are available here: Free Articles

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#56. A Summary of ‘Flash Boys: A Wall Street Revolt’ by Michael Lewis

Due to a complaint from W.W. Norton, this summary is no longer available. I apologize for the inconvenience. If you have a question or comment, please leave it in the comment box below.

Sincerely,
Aaron Thibeault