Chapter 9

CRISPR has two main components:

1. An enzyme that cuts DNA 2. A small piece of RNA that serves as a guide for the enzyme directing it to a specific sequence of DNA

What are some complications of Sickle Cell Disease?

1. Anemia 2. Extreme pain 3. Blood clots 4. Stroke 5. Death

Sickled cells tend to get stuck in the tiny blood vessels that feed tissues throughout the body, leading to:

1. Blood clots 2. Intense pain

Our DNA is continually being bombarded by environmental factors that can also damage DNA and cause mutations. These factors include:

1. Chemicals 2. Ultraviolet light 3. Radiation 4. Infectious agents like viruses

List the steps of how gene therapy cures sickle cell disease:

1. Hematopoietic stem cells with a mutated beta-globin gene are removed from a person with sickle cell disease 2. A virus is altered to carry the normal beta-globin gene 3. Stem cells infected with the virus receive the normal beta-globin gene, which gets stitched into the stem chromosome 4. Genetically engineering stem cells are grown in large numbers 5. Stem cells carrying the normal beta-globin gene are transfused back into the patient, where they produce normal red blood cells

What are some mutations that can be found under Frameshift Mutations?

1. Insertion mutation 2. Deletion mutation

What are some mutations that can be found under Rearranged Mutations?

1. Inversion mutation 2. Translocation mutation

Mutations are changes in the nucleotide sequence of DNA. There are several ways that a person can end up with a mutation:

1. It may have been inherited 2. It may have occurred randomly during DNA replication 3. It may have been the result of environmental insult

A few hundred miles away, in Boston, 20-year-old Manny Johnson was preparing to undergo a similar gene therapy procedure, this one pioneered by scientists at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center. The approach that these doctors are using takes advantage of the fact that the human body is capable of making two different versions of hemoglobin over the course of its life:

1. One during the fetal period 2. One during adulthood

List the different types of mutations:

1. Original DNA sequence (no mutation) 2. Point Mutations 3. Frameshift Mutations 4. Rearranged DNA Mutations

What are some mutations that can be found under Point Mutations?

1. Silent Mutation 2. Missense Mutation 3. Nonsense Mutation

Clots can also cause:

1. Stroke 2. Blockages in the lungs 3. Organ failure 4. And, ultimately, death

Sickle cell disease affects hundreds of thousands of people around the globe, primarily those living in:

1. Sub-Saharan Africa 2. The Saudi Arabian peninsula 3. Central India * And those individuals who can trace their ancestry to these areas

List the steps CRISPR uses to cure sickle cell patients:

1. The DNA-cutting enzyme is added to DNA containing the target sequence to be modified 2. The enzyme is designed to bind the target sequence and cut the DNA in this precise location 3. Once the DNA is cut, scientists can modify or add a specific DNA sequence in this locaiton

Adult hemoglobin contains:

1. Two alpha-globin subunits 2. Two beta-globin subunits

Normally, hemoglobin is a compact protein molecule made up of four interacting subunits:

1. Two alpha-globin subunits 2. Two beta-globin subunits

Fetal hemoglobin contains:

1. Two alpha-globin subunits 2. Two gamma-globin subunits

About 1 out of every ____ African American babies will be born with the disease

365

In the United States, ____ of all patients with sickle cell disease are African American

90%

What is a Mutation?

A change in the nucleotide sequence of a DNA molecule

What is Anemia?

A condition where there is a shortage of red blood cells capable of delivering oxygen to tissues

What is CRISPR?

A genome-editing tool based on a natural defense system in bacteria

Explain how gene therapy can be used to cure sickle cell disease

A modified virus serves as the vector to introduce a normal beta-globin gene to hematopoietic (blood-forming) stem cells isolated from a patient with sickle cell disease. Once stem cells have been obtained from the patient, they are infected with the engineered virus. The beta-globin gene carried by the virus is incorporated into a host cell's chromosome. The genetically modified cells are then grown in the lab, so that a large number of them can be introduced back into the patient, where they will produce normal beta-globin, which will be incorporated into normal hemoglobin in red blood cells that will not sickle

How can Inheritance cause mutation?

A mutation in the beta-globin gene can be inherited from either parent. If the mutation is inherited from both parents, then the offspring will have sickle cell disease

What is Point Mutation?

A mutation that alters a single DNA nucleotide

Who is David Williams?

A physician-scientist at Dana-Farber/Boston Children's and the team's lead scientific investigator, who says his group favors this "switching" approach because it takes advantage of a process that the body uses anyway. "Other trials are adding genes that encode fetal hemoglobin or corrected, non-sickling adult hemoglobin, without directly decreasing expression of the sickle hemoglobin gene," he says. "We predict our strategy is a more effective way to reduce or even eliminate the sickling of cells."

What are Missense Mutations?

A point mutation that changes the amino acid sequence of the encoded protein

What are Silent Mutations?

A point mutation that does not change the amino acid sequence of the encoded protein

What are Frameshift Mutations?

A shift in the reading frame, such that codons start and end at an alternative position

What is Gene Editing?

A way to change the sequence of a gene

In the United States, most sufferers of sickle cell disease are ____

African American

____ expression starts a few months before birth and continues into infancy and adulthood

Beta-globin

The situation is different in other countries. In 2018, a scientist in China announced that he had performed germ-line editing using CRISPR on two embryos that were subsequently implanted into a woman's uterus. The scientist edited a gene called ____, which makes a protein to which HIV binds to infect cells

CCR5

Correcting the genetic mistake with the tool is still a few years away. But at least one clinical trial now under way uses ____ to flip the switch to permit fetal hemoglobin expression in adults with sickle cell disease

CRISPR

____ allows scientists to edit DNA at very specific regions of the genome. Compared to other tools for genome editing, it is relatively quick, easy, and cheap

CRISPR

____, which are chemical agents that cause cancer, are a type of mutagen

Carcinogens

What is the effect of a inversion mutation on protein function?

Change in protein shape and function

What is the effect of a missense mutation on protein function?

Change in protein shape and function

What is Gene Therapy?

Correcting or replacing mutated genes as a treatment for a genetic disease

One way that a cell can develop a new mutation is during ____

DNA replication

____ can help reduce the frequency of episodes, though these medicines don't work for everyone

Drugs

How can a cell develop a new mutation during DNA replication?

Each time our cells replicate their DNA, there is a small chance that a mistake will occur—say, an A nucleotide is paired with a G, instead of a T. If this mistake is not corrected, it will lead to a permanent change in the DNA sequence—a mutation. This mutation will then be passed on as the cell divides and reproduces

All mutagens originate outside the body (T/F)

False

Hydroxyurea works for everyone (T/F)

False

Explain the experience of having sickle cell disease

For Jennelle Stephenson, a graduate student from Kissimmee, Florida, the pain had finally become unbearable. "Imagine there's an incredibly heavy object crushing you," she says. "You can't breathe, there's no air, and you feel like your bones are cracking from the pressure." The pain comes on without warning, often beginning with a tingling sensation in her back. Then it spreads to her arms, her legs, and even her cheekbones. When it's not the crushing sort of pain, it's sharp and localized—"like being stabbed over and over and over in same spot," she says. During these pain crises, only the strongest narcotics will help. To obtain these, Jennelle must travel to the emergency room. But doctors and nurses there are typically reluctant to give her the medications, concerned she might be faking it. In the meantime, she must endure the excruciating pain. Jennelle's experience, while dramatic, is all too typical for people with sickle cell disease. Pain is a constant threat, restricting their life choices.

In people with sickle cell disease, the original codon in the beta-globin mRNA, GAG, is changed to ____. As a result, when the mRNA is translated into protein, glutamic acid (Glu) in the normal protein becomes a ____. This amino acid change alters the physical shape and chemical properties of the protein

GUG, valine (Val)

Explain Germ-Line Gene Therapy

Genetic alterations made to cells that become sperm or eggs, or to early embryonic cells, are passed on to every cell in an offspring

Explain Somatic Gene Therapy

Genetic alterations made to somatic cells are not passed on to offspring

What is the difference between gene therapy and gene editing?

In gene therapy, entire genes are inserted or removed from a recipient cell. But what if it were possible to simply correct a genetic error in the original gene—for example, to edit out the mistaken "T" and replace it with the correct "A"? In fact, that goal may one day be possible thanks to the genome-editing tool CRISPR

Where do mutations like those that cause sickle cell disease come from?

In the case of sickle cell disease, the mutations are inherited, meaning they are passed from parents to children and are present in every cell of the child's body at birth

Why is sickle cell disease is more common in individuals from certain geographic areas?

In these environments, having one copy of the sickle cell mutation confers a benefit. The sickle cell mutation is found at high frequencies wherever the disease malaria is or has been common. Malaria is caused by a parasite that infects red blood cells. In environments where malaria is common, having just one sickle cell mutation—the condition called sickle cell trait—provides protection against malaria infection. This is why the mutation continues to occur at high frequency in populations of people living in those areas

Yet the field has had its share of failures as well. Most memorably, in 1999, a gene therapy trial ended in disaster when the patient, 18-year-old ____, died as a result of the procedure. The gene therapy was designed to fix a rare liver disease. Jesse developed a severe allergic reaction to the virus that was used to deliver the new gene to his liver cells. The scientist who led the trial admitted to not following his own procedures, and he shouldered some of the blame for the tragic result

Jesse Gelsinger

In 2017, the FDA approved two gene therapies for cancer, ____ and ____. Gene therapies for other diseases are not far behind

Kymriah, Yescarta

____ was the first patient enrolled on the trial at Dana-Farber/Boston Children's

Manny

How can the Environment cause mutation?

Many components of the environment, our food, and even our cells can cause mutations, such as: radiation (UV radiation, X-rays), chemicals (pollution and pesticides, smoking, alcohol, char), infectious agents (hepatitis C), cellular reactions (cellular processes produce mutagenic free radicals)

How can DNA Replication Errors cause mutation?

Mistakes can happen during DNA replication. Most, but not all, mistakes are corrected by repair enzymes. On average, 1 mutation occurs for every 10 billion base pairs that are replicated

____ target a specific DNA sequence, which can then be used to insert, delete, or alter a DNA sequence at that site.

Molecular tools

Although the United States does not officially ban the editing of DNA in human embryos, the ____, which funds most biomedical research in this country, currently prohibits it. In addition, the ____ is not allowed (by law) to approve clinical trials involving genetically modified human embryos

NIH, Food and Drug Administration (FDA)

____ and ____, given at the time of a pain crisis, can alleviate pain but will not prevent sickle cell disease

Narcotics, blood transfusions

What is the effect of a silent mutation on protein function?

No change; normal function

What are Somatic Cells?

Nonreproductive cells of the body

____ red blood cells carrying oxygen flow freely in the bloodstream

Normal

What is the effect of a nonsense mutation on protein function?

Protein is too short and therefore not functional

____ are essentially bags of hemoglobin

Red blood cells

What are Germ Cells?

Reproductive cells of the body

What does a red cell look like when a person does not have sickle cell disease?

Round, flexible, and carries abundant oxygen

What is the effect of a deletion mutation on protein function?

Severely modified sequence makes the protein not functional

What is the effect of a insert mutation on protein function?

Severely modified sequence makes the protein not functional

____ is an inherited genetic disorder

Sickle cell disease

____ red blood cells clump together and block the flow of blood and oxygen. They also do not survive as long as normal blood cells

Sickled

What is the effect of a translocation mutation on protein function?

Significant change in protein shape and function

____ are those that occur in any cell in the body other than sperm or egg cells. These mutations are not inherited but may cause disease in the individual that acquires them

Somatic mutations

How does CRISPR use the enzyme and small piece of RNA?

The RNA binds to DNA through complementary base pairing of the sort we have encountered before. Once the complementary match is found, the enzyme cuts the DNA in that precise location. The cell's DNA repair machinery then takes over to fill in the gap. If a supplementary piece of DNA is supplied along with the CRISPR enzyme, the cell will stitch this piece of DNA into the gap. Using CRISPR, scientists can introduce small deletions or additions at this cut site, or even replace one specific sequence of DNA with another

How did Sickle Cell Disease get its name?

The disease gets its name from the characteristic shape of red blood cells in people with the disease. Red blood cells carry oxygen throughout the body—oxygen that is critical for cells to carry out cellular respiration. Normally, a red blood cell is shaped like a jelly doughnut: round and squishy with a depression in the middle. In people with sickle cell disease, red blood cells become long and bent, like a sickle or a crescent moon

What is Hemoglobin?

The oxygen-carrying protein in red blood cells

Few effective treatments for sickle cell disease exist (T/F)

True

Mutations come in a variety of forms and can have many different effects (T/F)

True

Without mutations, there would be no evolution at all (T/F)

True

Explain how a Bone Marrow Transplant can cure sickle cell disease

With such a transplant, a person's entire blood-making system is wiped out with toxic chemicals and then replaced with that of a genetically compatible donor—assuming one can be found

Both adult and fetal hemoglobin contain two alpha-globin subunits. But where adult hemoglobin has two beta-globin subunits, fetal hemoglobin contains two gamma-globin subunits. The gamma-globin subunits of fetal hemoglobin are expressed during prenatal development, with that expression beginning to taper off around the time of birth. Beta-globin expression starts a few months before birth and continues into infancy and adulthood. The result of this gene expression pattern is...

a gradual loss of fetal hemoglobin after birth, and its replacement by adult hemoglobin.

Inversion mutation is when...

a group of DNA nucleotides are flipped to read in reverse order; different amino acid sequence in this location

Sickled red blood cells are less effective at carrying oxygen than normal red blood cells are, and they do not survive as long as normal blood cells. As a result, people with this condition often develop ____, a shortage of red blood cells capable of delivering oxygen to tissues

anemia

The particular gene affected encodes a protein called ____ that makes up one part of the hemoglobin molecule. What was an A-T base pair in the original version of the beta-globin gene is changed to a T-A base pair

beta-globin

Blood cells with abnormal hemoglobin...

block blood vessels and carry less oxygen

By the time Manny Johnson of Boston, Massachusetts, was 4 years old, he'd already had a stroke. A ____ formed in a vessel in his brain, blocking the flow of oxygen. Since then, he's received a blood transfusion nearly every month to prevent a dangerous clot from occurring again

blood clot

The only real potential cure for sickle cell disease is a ____, a physically grueling and risky procedure

bone marrow transplant

The gene therapy the NIH team developed is similar to the process used to engineer yeast to produce spider silk. As with the transgenic yeast, the scientists use a...

carrier molecule called a vector to deliver a new gene into the recipient cell. In this case, the vector is a genetically modified virus, and the gene is a beta-globin gene with the correct nucleotide sequence

Blood cells with normal hemoglobin...

carry oxygen freely through the bloodstream

Sickled red blood cells are less effective at...

carrying oxygen than normal red blood cells are, and they do not survive as long as normal blood cells

This stickiness of hemoglobin molecules is what...

causes red blood cells to sickle

Missense mutation...

change one nucleotide to another; different amino acid sequence in this location

Silent mutation...

change one nucleotide to another; no change in amino acid sequence

Nonsense mutation...

change one nucleotide; introduces early stop codon

A mutagen is a...

chemical or physical agent that can damage DNA by changing its nucleotide sequence resulting in mutations

Depending on where a point mutation occurs in a ____, it may—or may not—change the amino acid sequence of a protein

codon

Groups of three mRNA nucleotides, called ____, specify particular amino acids according to the genetic code

codons

Other mutations occur during our lifetime. In this case, cells that develop a mutation will pass that mutation on to their ____ every time they divide. As a result, only some cells in the body will have that mutation

daughter cells

Deletion mutation...

delete one or more nucleotides; shifts reading frame of every codon after the deletion

A few years later, in 2003, several people who received gene therapy developed cancer, and one died from the disease. In this case, the virus used to...

deliver the gene ended up landing next to a cancer gene, causing it to turn on abnormally. These deaths were a major setback for the field; it would be more than a decade before clinical trials started up again

Sickle cell disease primarily affects people who can trace their ancestors to...

equatorial regions of the globe

To avoid the problem of allergic reaction that caused Jesse Gelsinger's death, the virus is...

exposed to the stem cells outside of the body. Millions of copies of the genetically engineered stem cells are grown in the lab and then inserted back into the patient in the hope that they will take hold and begin producing normal hemoglobin

Because ____ does not contain beta-globin subunits, it will not cause sickling, even in people with sickle cell disease

fetal hemoglobin

Genetic engineering approaches are being used to express...

fetal hemoglobin and shut down expression of sickle hemoglobin in people with the disease

A person with the sickle cell mutation in the beta-globin gene will make perfectly normal fetal hemoglobin, since...

fetal hemoglobin does not contain beta-globin subunits, and will display no symptoms as an infant

In other cases, one or more DNA nucleotides may be inserted or deleted from genes, shifting the reading frame of that gene—that is, changing where a codon begins and ends. These types of mutations are known as ____

frameshift mutations

Not all mutagens originate outside the body. For example, some of the reactions that occur in the mitochondria during cellular respiration produce DNA-damaging molecules called ____. When cells attempt to repair this damage, the repairs may be carried out incorrectly, leading to a mutation

free radicals

Since a protein's shape determines its ____, hemoglobin molecules with these altered shapes are unable to effectively carry oxygen. Moreover, the long chains of hemoglobin molecules stretch the cell into its characteristic sickled form

function

The ____ subunits of fetal hemoglobin are expressed during prenatal development, with that expression beginning to taper off around the time of birth

gamma-globin

Scientists sometimes make a distinction between gene therapy and ____

gene editing

Scientists at several medical centers in the United States are developing forms of ____ designed to fix the genetic mistake that these individuals are born with

gene therapy

Thanks to advances in ____, this dismal picture is starting to improve

genetic engineering

Before a virus can be safely used in genetic engineering, it must be ____ so that it no longer contains the genes that allow it to replicate itself, kill cells, and cause illness. When that's done, all that's left are the tools it uses to insert DNA into the host chromosome, making it a handy gene delivery vehicle for gene therapy

genetically altered

Mutations are central to both ____ and ____—they are responsible for the diversity of traits that we see among individuals and among species

genetics, evolution

No matter how much Jennelle and Manny may personally benefit from their genetically engineered cells, they will not be free from all consequences of their genetic disease. That's because the changes are being made in only a subset of the somatic cells making up their body. They will still have the mutation in their _____—those that develop into sperm or eggs. That means they can still pass the mutation on to their children

germ cells

The only way to prevent that possibility would be to correct the genetic mistake in their...

germ cells or in an early embryo (changes in an early embryo will be present in virtually cells in the body, including germ cells). Such germ-line editing, while technically feasible, is quite controversial. That's because changing the DNA in germ cells affects not just one individual, but all of that person's descendants—and those future individuals cannot consent to having their genetic material altered

Mutations that occur in sperm or egg cells are ____ that can be passed on to offspring. These inherited mutations are then found in every cell of the offspring, including egg or sperm cells, and can be passed on to subsequent generations

germ-line mutations

People with two mutated copies of the beta-globin gene, however, will...

have sickle cell disease

The NIH scientists expose the viral vector containing the beta-globin gene to blood-forming stem cells, called ____, obtained from a person's blood. The virus infects these cells, and delivers its beta-globin payload to the nucleus of these cells. The beta-globin gene is then stitched into one of the host cell's chromosomes

hematopoietic stem cells

Altered ____ causes cells to take on a sickled shape, and interferes with the ability of red blood cells to carry oxygen to tissues.

hemoglobin

Scientists have known since the 1950s that sickle cell disease is the result of a single change in the nucleotide sequence of one gene. That change alters the shape of ____, the oxygen-carrying molecule inside of red blood cells

hemoglobin

One of the main existing treatments for sickle cell disease is a drug called ____, which can reduce the amount of sickling that occurs in a person's body

hydroxyurea

The drug hydroxyurea—mentioned earlier as a treatment for sickle cell disease—works by...

increasing the amount of fetal hemoglobin that a person makes in adulthood, which helps offset the amount of abnormal hemoglobin produced

Specifically, viruses reproduce by...

infecting host cells and delivering viral genes into the infected cells. An infected host cell transcribes and translates these viral genes as if they are its own, and the virus then uses these components to make even more copies of itself

Sickle cell disease was the first...

inherited genetic disease to be understood on a molecular level

Insertion mutation...

insert one or more nucleotides; shifts reading frame of every codon after the insertion

Similarly, the engineered viral vector carrying the new beta-globin gene naturally infects host cells, delivering the beta-globin gene into those cells. The beta-globin gene is...

inserted into one of the host cell's chromosomes, where it is replicated and retained as a stable component of the host cell's genome

A segment of DNA can "flip" within its normal chromosomal location; a change called an ____

inversion

One reason to be cautious about germ-line editing, from a strictly scientific standpoint, is that we don't always...

know what effect a mutation will have in different environments

In sickle cell disease, the amino acid change alters the physical shape and chemical properties of the beta-globin subunit, causing it to...

link up with other beta-globin subunits in neighboring hemoglobin molecules

During gene expression, DNA is first transcribed into ____, which is then translated into ____

mRNA, protein

CRISPR is such a new technology that there is not yet a lot of experience from which to learn. One concern with CRISPR technology is that it could...

make "off target" cuts in the genome, not just at the desired location. These unplanned changes could have serious consequences if they occur in genes that encode essential proteins.

The edited version of the gene shortens the CCR5 protein and...

makes cells more resistant to HIV infection. The woman later gave birth to the world's first CRISPR'd babies

The frequency of the sickle cell mutation is higher in areas where malaria is or has been common. While having two copies of the sickle cell mutation is harmful, having one copy protects against _____, which explains why this mutation is more frequent in certain parts of the world

malaria

Point mutations that change the amino acid sequence of a protein are called ____

missense mutations

Not all mutagens originate outside the body. For example, some of the reactions that occur in the ____ during cellular respiration produce DNA-damaging molecules called free radicals. When cells attempt to repair this damage, the repairs may be carried out incorrectly, leading to a mutation

mitochondria

CRISPR (which stands for "clustered regularly interspaced short palindromic repeats") is a kind of...

molecular scissors that bacteria use to chop up viruses and thereby defend themselves from infection. Scientists have adapted this set of bacterial scissors to make it an exquisite tool for genetic engineering

Translocation mutation...

move segments of DNA from one chromosome to another, fusing portions of different genes together

Physical or chemical agents that cause mutations are called ____

mutagens

The degree of sickling depends on how much ____ is present in a red blood cell, relative to the amount of normal hemoglobin

mutated hemoglobin

A change in the nucleotide sequence of a DNA molecule is called a ____

mutation

Viruses make good vectors because they...

naturally inject genetic material—their own—into host cells as part of their normal life cycle

In many cases, the shape of the protein is altered in a way that makes it ____. In other cases, the mutation changes the shape of the protein in a way that makes it ____

nonfunctional, overly active

Mutations alter the...

nucleotide sequence of DNA

As discussed in Chapter 7, we all have two copies of every gene—one copy from our biological father and one copy from our biological mother. People can have...

one, two, or no mutated beta-globin genes, depending on which versions they inherit from their parents

The type of mutation that causes sickle cell disease is called a ____; it alters a single DNA nucleotide

point mutation

In places without malaria, the mutation has no such...

protective effect. In addition, those who happen to inherit two copies of it suffer severe, painful consequences in the form of sickle cell disease

Large inversions and translocations can fuse portions of different genes together, creating new ____ with novel activity

proteins

Whole blocks of DNA can be ____ as a result of mutation

rearranged

Sickle cell disease is an inherited genetic disorder that causes...

red blood cells to take on a sickled shape and carry less oxygen

The first trials of gene therapy approaches in people were conducted in the early 1990s. A 4-year-old girl with a...

severe immune deficiency became the first person to receive successful gene therapy: she was cured of her disease

Ultimately, the impact of a mutation depends on how it affects the ____ of a protein

shape

People with ____ experience anemia, episodes of severe pain, and other complications due to clots and blockages in blood vessels.

sickle cell disease

Point mutations that do not change the protein sequence are called ____

silent mutations

Scientists have known since the 1950s that sickle cell disease is the result of a...

single change in the nucleotide sequence of one gene

No matter how much Jennelle and Manny may personally benefit from their genetically engineered cells, they will not be free from all consequences of their genetic disease. That's because the changes are being made in only a subset of the ____ making up their body

somatic cells

In the case of sickle cell disease, the mutation causes the beta-globin subunits of hemoglobin to become ____ and attract the beta-globin subunits from other hemoglobin molecules

sticky

If a mutation changes the coding region of a gene, the resulting protein may have an altered ____ and ____

structure, function

Gene therapy has been a goal of medical science since the 1970s. Ever since scientists learned how to cut and splice together pieces of DNA in the lab, they have been...

tantalized by the prospect of using such techniques to fix genetic errors and cure genetic diseases in people

A person with the sickle cell mutation in the beta-globin gene will make perfectly normal fetal hemoglobin, since fetal hemoglobin does not contain beta-globin subunits, and will display no symptoms as an infant. However, as beta-globin expression increases...

the adult hemoglobin will be of the sickling type, and the individual will start to experience symptoms of the disease

In principle, CRISPR could enable scientists to correct the genetic mistake that causes sickle cell disease in the first place—by swapping in a small piece of DNA with the nonmutated sequence to replace the mutated version in a person's blood stem cells. The cells with...

the correct sequence would produce only healthy hemoglobin, so the person would no longer experience symptoms of the disease

In other words, whether a particular mutation provides a survival advantage, or is neutral or harmful, often depends on...

the environment where a person with that mutation lives

People with one copy of the mutated beta-globin gene and one copy of a normal beta-globin gene are carriers of the condition, in other words...

they typically do not experience sickling of their cells and are said to have sickle cell trait

Segments of DNA can trade places between different chromosomes; a change called ____

translocations

The Dana-Farber/Boston Children's team's goal is to use genetic engineering techniques to...

turn on the expression of fetal hemoglobin and turn off the expression of adult hemoglobin. In essence, they are trying to flip a genetic switch so that Manny's normal fetal hemoglobin will be the only hemoglobin he produces

Both adult and fetal hemoglobin contain ____

two alpha-globin subunits

Both adult and fetal hemoglobin contain two alpha-globin subunits. But where adult hemoglobin has ____, fetal hemoglobin contains ____

two beta-globin subunits, two gamma-globin subunits

The NIH trial that Jennelle found involved using genetic engineering techniques to introduce a new gene into her blood cells. The new gene encodes a...

version of beta-globin that doesn't cause cells to sickle. The person still makes some abnormal hemoglobin from the mutated gene, but the engineered version of beta-globin is present in high enough amounts to prevent red blood cells from sickling

Recall that ____ are noncellular entities consisting of a protein "coat" surrounding genetic material

viruses

Scientists around the world condemned the Chinese scientist. Many said the experiment was reckless, given that...

we don't know enough about the edited gene to fully anticipate unintended consequences of its editing and that there are other ways to prevent HIV infection