Biology & Biomedical Issues - Exam 2

What is genetic testing?

A medical test that examines a person's DNA to look for changes or mutations in their genes, chromosomes, or proteins that may be linked to certain diseases or health conditions

What are the different purposes of genetic testing?

• Diagnostic: Find the cause of symptoms → “Do I have a disease?”

• Predictive/pre-symptomatic: Estimate future disease risk → “Could I have a disease in the future?”

• Carrier: Identify gene mutations that could be passed to children

• Prenatal: Check for genetic conditions before birth

• Newborn screening: Identify conditions early in life

• Preimplantation: Test embryos for certain genetic conditions

• Pharmacogenomic: a person may need a different medication or dosage because of their genetic makeup

How is a genetic test different from other medical tests

A genetic test analyzes your permanent DNA code to identify inherited changes or risks, whereas traditional medical tests measure temporary, changing bodily states like blood sugar, cholesterol, or infection levels

Carrier status

Has a genetic mutation associated with a disease but usually does not show symptoms of that disease.

- Typically has one mutated copy of a gene and one working copy for autosomal recessive diseases

- Can pass the mutated gene to their children.

- Usually does not have the disease themselves

What is Carrier screening? When might this be done?

A type of genetic test that determines whether a person carries a genetic mutation associated with an inherited disease, even if they do not have symptoms of the disease themselves

• Can be done before pregnancy, after pregnancy, or when there is a family history

Afflicted status

Has the genetic disease itself, meaning the genetic changes cause the condition to develop.

- For an autosomal recessive disease, the person typically inherits two mutated copies of the gene.

- May experience symptoms, depending on the disease.

- May pass disease-associated mutations to their children

What is the role of a Genetic Counselor?

A healthcare professional who helps individuals and families understand genetic conditions, genetic testing, and the risk of passing genetic diseases to their children

Non directiveness

A communication approach where the counselor presents balanced, unbiased medical and genetic information without pressuring or coercing the patient toward a specific decision

Prenatal tests conducted during pregnancy

• Amniocentesis: A small sample of amniotic fluid surrounding the baby is collected using a thin needle. The fluid contains fetal cells that can be tested for certain genetic and chromosome conditions

• Chorionic villus sampling: A small sample of placental tissue is collected and tested for specific genetic conditions or chromosome abnormalities

Prenatal tests before implantation (IVF or other reproductive tech)

Preimplantation genetic testing: Test embryos for selected genetic conditions

What is Pre-implantation testing? Why would someone do this?

A type of genetic testing performed on embryos created through in vitro fertilization (IVF) before an embryo is transferred into the uterus.

• People may do this to reduce risk of passing on a disease, identify chromosomal abnormalities

Prenatal ethical concerns

• Limited treatment options → A condition is detected, but treatment may be unavailable or limited.

• False positive/negatives → A test incorrectly indicates whether a condition is present causing unnecessary stress, false reassurance, or decisions based on inaccurate information

• “Perfect baby” → Genetic selection may encourage choosing preferred traits possibly creating discrimination against others, Where should society draw the line between preventing serious disease and selecting preferred traits

• Late-onset diseases → Testing reveals a condition that may develop much later in life.

• Wrongful birth → Parents claim negligence deprived them of an informed reproductive choice

• Wrongful life → A claim made on behalf of a child alleging negligent conduct led to their birth with a serious condition.

General ethical concerns regarding genetic testing

• Privacy → Who can see genetic results?

• Discrimination → Could genetic information be used unfairly by an employer/insurance company?

• Psychological effects → Could results cause emotional distress?

• Family implications → Should relatives be informed?

• Reproductive choices → How might results affect decisions about having children?

What is population screening?

The process of testing a large group of people, often people who do not have symptoms, to identify those who may have a disease, health condition, or increased risk of developing one

What are examples of population screening?

Newborn screening, blood pressure checks, mammograms, and carrier screening

What are ways to do population screening effectively?

Use an appropriate, accurate test and ensure access to follow-up and treatment.

What are the errors to avoid?

False positives, false negatives, overdiagnosis, poor follow-up, and screening without sufficient evidence of benefit.

What is Specificity vs. sensitivity in testing?

Sensitivity: How well a test correctly identifies people who have the disease.

• You want high sensitivity (fewer false negatives)

Specificity: How well a test correctly identifies people who do not have the disease

• You want high specificity (fewer false positives)

How to calculate specificity vs. sensitivity

Sensitivity = True Positive / True positive + False Negative

Specificity = True negative / True negative + False Positive

What is Newborn Screening? When is this done and why?

A group of tests performed on babies shortly after birth to check for certain genetic, metabolic, hormonal, and other medical conditions that may not be obvious when the baby is born

• Usually within the first 24–48 hours after birth, depending on the hospital and state requirements

• Helps identify conditions that may not cause symptoms immediately but can become dangerous if left untreated

Mandatory screening

Screening that is required by law or an established policy

• Usually required, with exceptions depending on the law or policy.

  • Newborn screening required under state law for certain conditions.

Elective screening

Screening that a person chooses whether or not to undergo.

• The individual decides whether to participate

  • Often aims to assess personal health risks or obtain genetic information

What are the investigational requirements for a new drug/gene therapy?

• Clone fully characterized – The gene being used must be thoroughly understood and studied

• The gene must be delivered to the appropriate target cells/tissue – Researchers must be able to get the therapeutic gene into the cells that need it.

• The gene must be expressed properly in the target cells – The inserted gene must function and produce the needed protein.

• The disease must not be treatable by other strategies.

• Data available from preliminary studies, human cells – There must be supporting research showing that the treatment has potential.

What are the different stages of Clinical trials? What is the purpose of each stage?

• Phase I: Safety → Small group, determines whether the treatment is safe

• Phase II: Effectiveness → Tests on a larger group, determines whether the treatment actually works

• Phase III: Confirmation → Even larger group, long term, side effects, efficacy, dosing

• Phase IV: Available to the public → Goes on the market, post clinical trial, longer term effects

What is gene therapy?

Any procedure intended to treat or alleviate disease by genetically modifying the cells of a patient

• Somatic cell gene therapy

• Germ line gene therapy

Somatic cell gene therapy

• Treats disease symptoms

• Non-reproductive body cells, such as those in lung tissue, muscle, or blood

• Can still pass down disease to future offspring (non heritable)

What is a vector?

A carrier vehicle—often likened to a microscopic delivery truck—used to transport therapeutic genetic material (such as a healthy gene or gene-editing tool) safely into a patient's target cells

In vivo

• A form of somatic gene therapy

• Genetic material is transferred directly into cells within a patient

• The genetic cargo is packaged inside a vector which navigates the body to find and enter the target cells

Ex vivo

• A form of somatic gene therapy

• Patient cells are extracted

• Modified in a laboratory using the vector

• Then reintroduced into the body

What is Kymriah (CAR T-cell therapy)

• A type of ex vivo gene therapy

• Used to treat certain blood cancers such as leukemia and lymphoma

• Takes a patient's own immune cells, genetically modify them so they can recognize cancer cells, and put them back into the patient's body to fight the cancer

How CAR T therapy works

• Leukapheresis: Doctors collect the patient's blood and separate out the T cells, which are white blood cells that normally help the immune system fight infections and cancer

  • Reprograms a patient's T cells to recognize cancer cells more effectively

• Reprogrammed Cells: Scientists use an inactive virus (a viral vector) to insert new genetic instructions into the T cells

• Expansion: The genetically modified T cells are grown and multiplied in the laboratory to produce enough cancer-fighting cells.

• Quality check: Testing occurs before the CAR T cells go back to the patient

• Chemo: Lympohodepleting chemo is given to the patient to reduce white blood cells to help the body accept the new reprogrammed CAR T cells

• Infusion: CAR T cells are delivered into the patients bloodstream

• Cell death: the CAR T cells recognize cancer cells and attach to them leading to cell death

How is the vector used in CAR T cell therapy?

• Scientists prepare the gene that contains instructions for making the CAR receptor.

• They put that genetic material into a vector.

• The vector delivers the genetic material into the patient's T cells.

• The T cells use those instructions to produce CAR receptors.

• The modified T cells can now recognize and attack cancer cells.

  • Vector = Delivery truck

How is Kymriah different than the process used for OTC?

• Kymriah = Ex vivo (Take cells OUT → Modify OUTSIDE → Put cells BACK IN)

• OTC = In vivo (Put the vector INTO the body → Deliver the gene to liver cells → Liver cells produce the enzyme)

Germ line cell gene therapy

• Defective genes replaces in germ cells

• Reproductive cells (sperm or egg cells) or early-stage embryos

• The genetic modifications can be passed down (heritable)

What are the reasons for not doing germ-line?

Most researchers agree that it should not be done in humans

Concerns:

– Risk to future generations

– Reduction of genetic diversity

– Not necessary

– Current technology not ready

Are there other better options available than modifying embryos?

• Preimplantation Genetic Testing (PGT)

• Third party gametes (donated sperm/eggs)

• Somatic gene therapy

What are some of the difficulties with gene therapy?

• Getting the gene to the correct cells

• The body's immune system may recognize the viral vector as foreign and attack it

• Gene inserts into an unintended DNA location

• High cost

• Unknown or delayed side effects

What makes gene therapy so expensive?

Can cost between $1 million and over $3 million per dose

• Massive research investments

• Tiny patient populations

• Complex, manual manufacturing processes

What is a genetically modified organism?

Any plant, animal, or microorganism whose genetic material (DNA) has been deliberately changed in a laboratory using modern biotechnology or genetic engineering

What is recombinant DNA?

DNA that has been created by combining genetic material from two or more different sources

What is recombinant protein?

A protein produced by a cell (such as a bacterial or yeast cell) that has been genetically modified to contain DNA instructions for making that protein

• Produced by using recombinant DNA

How does cloning in bacteria work to make a lot of a product (protein) of interest?

• Isolate DNA from 2 sources

• Cut both DNAs with the same restriction enzyme

• Mix the DNA together

• DNA ligase connects the DNA

• Put recombinant plasmid into bacterial cell

• Bacteria multiply

• Identify the bacteria and collect the protein.

Isolate DNA from 2 sources

Scientists collect two things:

• A bacterial plasmid (a small, circular piece of DNA found in bacteria).

• The donor DNA containing the gene that makes the desired protein.

Think of the plasmid as an empty ring that will carry the new gene.

Cut both DNAs with the same restriction enzyme

Scientists use special enzymes called restriction enzymes to cut the plasmid and the donor DNA.

This creates matching ends so the pieces can fit together, almost like puzzle pieces.

Mix the DNA together.

The desired gene joins with the bacterial plasmid because their matching ends pair together.

Now the plasmid contains the new gene!

DNA ligase connects the DNA

An enzyme called DNA ligase seals the pieces together, creating a complete circular DNA molecule.

This new DNA is called recombinant DNA because it combines DNA from two different sources

Put the recombinant plasmid into a bacterial cell

Scientists insert the new plasmid into a bacterium.

The bacterium now carries the gene that tells it how to make the desired protein.

Bacteria multiply (make clones)

The bacteria reproduce by dividing.

As they multiply, they make copies of the recombinant plasmid, meaning there are many copies of the desired gene.

Identify the bacteria and collect the protein

Scientists identify the bacteria that contain the desired gene.

They then grow the bacteria and collect the protein they produce.

What is the vector for modifying bacteria?

A plasmid

• A vector is the carrier that delivers new genetic material

• The plasmid carries the new desired gene

What is rBGH?

A genetically engineered hormone given to dairy cows to increase the amount of milk they produce

How is rBGH made?

Use genetically engineered bacteria

• Scientists take the gene responsible for producing bovine growth hormone from cow DNA

• They insert that gene into bacterial DNA (specifically, a plasmid)

• The genetically engineered bacteria produce the bovine growth hormone

• Scientists collect the hormone and inject it into dairy cows

• The hormone stimulates the cows to produce more milk

Why do we have rBGH ?

• Cows naturally produce BGH

• If they had more BGH, they would produce more milk

• Scientists manufacture more of this hormone which is then called rBGH to differentiate from the natural BGH

• Farmers inject additional rBGH into dairy cows so they produce more milk

What is a transgenic organism?

An organism that contains a gene from another organism

• contains foreign DNA

GMO vs Transgenic organism

• GMO: An organism whose genetic material has been altered

• Trangenic: An organism that contains a gene from another organism

  • All transgenic organisms are genetically modified, but not all genetically modified organisms are transgenic (since it could be your own DNA altered, not something foreign)

What is pharming?

A process where scientists genetically modify plants or animals to produce useful medical proteins.

• Instead of using bacteria, scientists use plants or animals as biological factories

• farming + pharmaceuticals

Why can’t all recombinant proteins be made in bacteria?

Bacteria are too simple to make certain complex proteins correctly

• Instead, scientists use genetically modified plants or animals (pharming)

How was the tomato modified to reduce/slow ripening? How is this a genetic modification?

• Pectinase causes ripening in tomatoes and other produce

• A gene inserted into tomatoes that prevents pectinase mRNA translation slows ripening

• They used genetic engineering to introduce an extra gene that blocked or reduced the production of pectinase

What is anti-pectinase gene?

An engineered, reverse-orientation gene introduced into plants to suppress the production of pectinase enzymes

• By blocking this breakdown, the anti-pectinase gene effectively slows down fruit softening, extending shelf life and preventing rapid rotting

Why would a farmer want a plant that has the Bt gene? How does it change how they grow their crop?

It makes the plants resistant to certain insect pests

• Plants can protect themselves

• Fewer insecticides

• Results in better yields

  • Bt crops still require monitoring and pest management because insects can develop resistance over time

Why would a farmer want to grow Roundup Ready soybeans? How does it change how they grow their crop?

They are genetically modified to survive being sprayed with Roundup, a weed-killing herbicide.

• Allows farmers to kill weeds without killing their soybean crops

• Farmers can control weeds more easily and efficiently.

  • Repeated glyphosate use can cause weeds to develop resistance

What are some example plant modifications that are beneficial for the consumer and not just the producer?

Modifications that make food healthier

• Golden rice → More vitamin A

• Purple tomato → High antioxidants

What agency decides which bioengineered foods need to be labeled?

The USDA (United States Department of Agriculture)

• oversees the National Bioengineered Food Disclosure Standard and determines which foods fall under the bioengineered food labeling requirements.

What are 4 reasons that genetically modified animals are made?

• Animal “enhancement”

• Research

• Pharmaceuticals

• Xenotransplants

What is Xenotransplantation?

The process of transferring or transplanting living cells, tissues, or organs from one species into another

• Scientists genetically modify pigs so their organs are more compatible with the human body.

• A pig's heart or kidney may then be transplanted into a human.

• Genetic modifications help reduce the chance that the human immune system will reject the animal organ

What is a benefit to having a recombinant protein expressed in chicken egg whites or goat milk?

Provide an easy way to collect and harvest large amounts of recombinant proteins

• Scientists genetically modify a chicken or goat by inserting a gene that contains instructions for making a specific human protein.

• The animal produces that protein in its egg whites or milk.

• Scientists collect the eggs or milk and extract and purify the protein.

• The purified protein can then be used to make medicine.

What is the process for getting the recombinant protein to be expressed in your animal of choice for pharming?

• Identify the gene

• Attach the gene to a promoter

  • A promoter is a DNA sequence that acts like an on/off switch, controlling when and where the gene is expressed

• Insert the gene into the animal's DNA

• Create a transgenic animal

• Collect protein

• Purify the protein

Why was the Atlantic salmon modified?  If you eat salmon at a restaurant, would you know if it was AquaAdvantage salmon?

To grow faster than conventional farm-raised Atlantic salmon

• Restaurants are exempt from the federal bioengineered food labeling requirement

What are the functions of blood?

• Transportation

• Protection

• Regulation

• Clotting

Functions of blood: Transportation

Blood carries important substances throughout the body.

- Oxygen: Carries oxygen from the lungs to body cells.

- Nutrients: Delivers nutrients from food to cells.

- Waste: Carries carbon dioxide and other wastes to organs that remove them.

- Hormones: Transports hormones to different parts of the body.

Functions of blood: Regulation

Blood helps keep the body balanced.

• Regulates body temperature.

• Maintains proper pH (acid-base balance).

• Maintains fluid balance in the body

Functions of blood: Protection

Blood protects the body from infections and diseases.

• White blood cells fight bacteria, viruses, and other harmful organisms.

• Antibodies help recognize and destroy harmful substances.

Functions of blood: Clotting

Blood prevents excessive blood loss when you get injured.

• Platelets gather at the injury.

• Clotting proteins help form a blood clot.

• The clot seals the wound and helps stop bleeding.

What are the three major components of blood?

• Plasma → Trasports substances

• Formed elements

  • Red blood cells (erythrocytes)

  • White blood cells (leukocytes)

    • Platelets are also a major component of blood. They help blood clot and stop bleeding

How does plasma help to maintain homeostasis of the body?

Helps keep the body functioning properly by balancing temperature, water, pH, and important substances

• distributes heat throughout the body, helping maintain a stable temperature

• contains substances called buffers that help keep blood from becoming too acidic or too basic

• carries nutrients, hormones, electrolytes, and waste products throughout the body

Where in the body are blood cells (formed elements) produced?

Red bone marrow

Hematopoiesis

The process of producing blood cells

• Ensures your body constantly replaces old or dying blood cells with new ones

What are the formed elements of the blood?

• Red blood cells (Erythrocytes)

• White blood cells (Leukocytes)

• Platelets (Thrombocytes)

Red blood cells (Erythrocytes)

• Carry oxygen from the lungs to the rest of the body.

• Carry some carbon dioxide from body tissues back to the lungs.

• Contain a protein called hemoglobin, which binds to oxygen.

White blood cells (Leukocytes)

• Protect the body against infections and diseases.

• Fight bacteria, viruses, and other foreign invaders.

• Help the immune system defend the body.

Platelets (Thrombocytes)

• Help blood clot when a blood vessel is damaged.

• Gather at an injury to form a platelet plug.

• Help stop bleeding and prevent excessive blood loss.

What carries oxygen in the blood? What protein is key to the process?

Red blood cells

• They use hemoglobin to pick up and carry oxygen

Oxyhemoglobin

• Oxygen is attached

• Forms when blood picks up oxygen in the lungs

• Carries oxygen to body tissues

Deoxyhemoglobin

• Without oxygen attached

• Forms after oxygen is released to body tissues.

• Travels back toward the lungs to pick up more oxygen.

Why does malaria cause anemia?

The parasite infects and destroys red blood cells.

• A malaria parasite enters the bloodstream.

• The parasite infects red blood cells and reproduces inside them.

• The infected red blood cells burst, releasing more parasites.

• This destroys red blood cells, reducing the amount of hemoglobin in the blood.

How is malaria transmitted?

Through the bite of an infected female mosquito

• The mosquito bites a person and injects malaria parasites into their bloodstream.

• The parasites travel to the liver and multiply.

• They eventually enter red blood cells, where they continue multiplying.

  • The mosquito is the vector since they carry and transmit the disease

Who is the universal donor?

• O-negative

• Its red blood cells do not have A, B, or Rh antigens on their surface.

• This means it can donate red blood cells to all eight common blood types.

Who is the universal recipient?

• AB positive

• People with AB+ blood have A, B, and Rh antigens.

• They do not have anti-A or anti-B antibodies, so they can receive red blood cells from all eight common blood types

What happens if you receive an incorrect blood transfusion?

Your immune system recognizes the donated red blood cells as foreign and attacks them

• Can cause a transfusion reaction

  • Antibodies attack the incompatible red blood cells.

  • Red blood cells clump together (agglutination).

  • Red blood cells can burst open (hemolysis).

  • This can cause kidney damage, shock, organ failure, and potentially death

An Rh- women is pregnant. Why would they give her a RhoGAM shot towards the end of her pregnancy?

To prevent her immune system from attacking her baby's red blood cells if the baby is Rh-positive (Rh+).

• The mother has Rh-negative blood, meaning her red blood cells do not have the Rh antigen.

• The baby may have Rh-positive blood, meaning the baby's red blood cells have the Rh antigen.

• During pregnancy or delivery, some of the baby's blood can enter the mother's bloodstream.

• The mother's immune system may recognize the baby's Rh-positive blood cells as foreign and create antibodies against them.

• These antibodies could attack the red blood cells of a future Rh-positive baby, causing anemia and other serious complications

What does the RhoGAM shot do?

• Prevents the mother's immune system from making antibodies against Rh-positive blood cells.

• Helps protect the current and future pregnancies.

• Is commonly given around 28 weeks of pregnancy and again within 72 hours after delivery if the baby is Rh-positive.

What are the two stages that occur when a blood clot (coagulation) is formed?

• Formation of a platelet plug

• Formation of a fibrin clot

  • Caused by a damage to a blood vessel

Formation of a platelet plug

• A blood vessel gets damaged or injured.

• The damaged blood vessel releases signals that activate platelets.

• Platelets stick to the damaged area and to one another.

• They form a temporary platelet plug to help stop bleeding.

Formation of a fibrin clot

• A series of chemical reactions activates clotting proteins (clotting factors) in the blood.

• These reactions produce an enzyme called thrombin.

• Thrombin converts a protein called fibrinogen into fibrin.

• Fibrin forms a mesh-like network around the platelet plug.

• This strengthens and stabilizes the clot, helping stop bleeding

What diseases interfere with blood clotting?

• Hemophilia → a genetic disease that due to mutations in one of the

  genes encoding the clotting factors, thus the fibrin clot is not formed

  • Blood does not clot properly

  • People may bleed longer than normal

• Thrombocytopenia → a person has an abnormally low number of platelets in their blood

  • Platelets help form the platelet plug during blood clotting so without platelets, the body struggles to form clots to prevent excess bleeding

What is the cardiovascular system composed of?

• Heart → pumps blood throughout the body

• Blood vessels → Tubes that carry blood throughout the body

• Blood → transports oxygen, nutrients, hormones, and waste products throughout the body

Types of Blood Vessels

• Arteries

  • Arterioles

• Veins

  • Venules

• Capillaries

  • Capillary bed

Arteries

Large blood vessels that carry blood away from the heart and toward the body's organs and tissues

• They usually carry oxygen-rich blood

• Have thick, strong, elastic walls

Arterioles

Smaller branches of arteries that carry blood from the arteries to the capillaries

• They help control how much blood flows into the capillaries

Capillaries

Extremely tiny blood vessels with very thin walls.

• They allow oxygen, nutrients, and waste products to be exchanged between the blood and body tissues