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Bio 1 General Biology – Exam 3 Outline Cell Division & Reproduction (Ch. 6) During this lecture, you will learn… 1) What it is that one generation passes on so that the next generation can be formed. 2) What controls the development of a living thing as it goes from being a microscopic cell to a larger organism. 3) How it is that the adult body is able to build muscle or repair a wound. I. The Role of DNA in Cell Division A. What controls cell reproduction/development? B. DNA contains an organism’s genome (the complete set of that organism’s genetic information strung together in functional units called genes that lay long the double helix) 1. Human genome is 3 billion base pairs long and includes 20,000 – 25,000 genes. We are born with a huge volume of info that has been amassed and edited over 3.8 billion years of evolution. 2. There is not just one copy of this genome in an organism. Most cells in an organism contain a complete copy of that organism’s genome. A given cell expresses or puts to use only parts of this genome. Different genes are active in different cells. This is what distinguishes a liver cell from a muscle cell. 3. Cells duplicate yet they still have a complete set of a genome, so the genome must duplicate too. C. What is passed on to the next generation? II. DNA & Chromosomes A. DNA is not just one long straight, double helix. It is divided up and packaged into units called chromosomes “colored bodies” 1. Chromosomes a. Each chromosome contains a single, long DNA molecule bearing thousands of genes. b. Number of chromosomes in a cell, like the number of genes, depends on the species. (Ex. humans cells = 46, onion cells = 15, dog = 78) c. Most of time, chromosomes exist as diffuse mass of very long fibers (the total DNA in a single human cell’s 46 chromosomes would stretch to about 6 feet long!) d. As cell prepares to divide, its fibers coil up, forming compact chromosomes and then are clearly visible under the microscope. 2. Sister chromatids

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Page 1: Cell Division & Reproduction (Ch. 6)

Bio 1 General Biology – Exam 3 Outline

Cell Division & Reproduction (Ch. 6)

During this lecture, you will learn… 1) What it is that one generation passes on so that the next generation can be formed. 2) What controls the development of a living thing as it goes from being a microscopic cell to a larger organism. 3) How it is that the adult body is able to build muscle or repair a wound. I. The Role of DNA in Cell Division A. What controls cell reproduction/development?

B. DNA contains an organism’s genome (the complete set of that organism’s genetic information strung together in functional units called genes that lay long the double helix)

1. Human genome is 3 billion base pairs long and includes 20,000 – 25,000 genes. We are born with a huge volume of info that has been amassed and edited over 3.8 billion years of evolution.

2. There is not just one copy of this genome in an organism. Most cells in an organism contain a complete copy of that organism’s genome. A given cell expresses or puts to use only parts of this genome. Different genes are active in different cells. This is what distinguishes a liver cell from a muscle cell.

3. Cells duplicate yet they still have a complete set of a genome, so the genome must duplicate too. C. What is passed on to the next generation?

II. DNA & Chromosomes A. DNA is not just one long straight, double helix. It is divided up and packaged into units called chromosomes

“colored bodies” 1. Chromosomes a. Each chromosome contains a single, long

DNA molecule bearing thousands of genes. b. Number of chromosomes in a cell, like the

number of genes, depends on the species. (Ex. humans cells = 46, onion cells = 15, dog = 78)

c. Most of time, chromosomes exist as diffuse mass of very long fibers (the total DNA in a single human cell’s 46 chromosomes would stretch to about 6 feet long!)

d. As cell prepares to divide, its fibers coil up, forming compact chromosomes and then are clearly visible under the microscope.

2. Sister chromatids

Page 2: Cell Division & Reproduction (Ch. 6)

B. Matched pairs (homologous) of chromosomes 1. A typical body cell (somatic cell) in humans has 46

chromosomes. 2. Chromosomes come in pairs that are close but not

exact matches. 3. The 46 chromosomes we have come to us as 23

chromosomes pairs, 23 from each parent; each chromosome from mother matching with one from father.

Ex. one from father coding for red hair while one from mother codes for blond hair 4. Homologous chromosomes carry the same sequence of

genes controlling the same inherited characteristics. If a gene influencing eye color is located in a particular place on one chromosome then the homologous chromosome has a similar gene for eye color there. However the two genes may be slightly different versions (Ex. blue from dad and brown from mom)

You are the product of the specific genes that are being expressed!

C. Exception to the matched pairs rule

How does a baby grow, a plant develop, or a wound heal? III. Cell Division

A. Steps of cell division (Cell Cycle): 1. Interphase (G1, S, & G2 phases) 2. Mitotic Phase (M phase) a. Mitosis b. Cytokinesis

3. How long does this cycle take? a. As many as 25 million cell divisions

are happening in your body every second!

b. Most human brain cells are formed in first 3 months of embryonic existence and live for decades, with

very few of them dividing again. Stem cells in human bone marrow never stop dividing as they produce blood cells

Page 3: Cell Division & Reproduction (Ch. 6)

B. Mitosis – cell division that produces body cells for organism growth and maintenance. Cell division of somatic

cells (all cells in organism except for those that become eggs or sperm) Watch Amoeba Sisters Mitosis: The Amazing Cell Process that Uses Division to Multiply! Steps of Mitosis: Prophase, Metaphase, Anaphase, Telophase (PMAT) Mitosis produces somatic (body) cells for organism growth and maintenance! Watch course website animations on Mitosis and Mitosis Bioflix Animation

Page 4: Cell Division & Reproduction (Ch. 6)

IV. When Mitosis Goes Wrong Cancer – disease of the cell cycle Cancer cells have malfunctioning cell cycle control systems so they divide excessively Watch Amoeba Sisters The Cell Cycle and Cancer Go to this website: http://www.cancer.gov/ , click on “What Is Cancer? ” under the heading “Cancer Topics” and read about the following types of cancers and tumors: A. Types of cancers are named according to where they start, so state the tissues or body system that they start in: 1. Carcinoma 2. Sarcoma

3. Leukemia 4. Lymphoma/myeloma

B. Types of Tumors: Define each tumor type 1. Benign tumor 2. Malignant (metastatic) tumor

C. Cancer Treatments

1. Radiation therapy – tumors are exposed to high energy radiation which disrupts cell division 2. Chemotherapy – uses drugs to disrupt cell division Ex. Vinblastine - obtained from the periwinkle plant native to tropical rainforests in Madagascar Taxol - found in bark of the Pacific yew tree found mainly in northwestern U.S.

Since cancer cells are more likely to be dividing at any given time than normal cells, radiation and chemotherapy can often destroy cancer cells without seriously injuring normal cells. However, damage to normal cells sometimes occurs and causes nausea, hair loss, and possible sterility

3. Hormonal therapy – prevents cells from receiving hormonal signals needed for cell growth and division Ex. Tamoxifen

4. Biological therapy (Immunotherapy) – uses the body's immune system to fight cancer

Page 5: Cell Division & Reproduction (Ch. 6)

D. Prevention of Cancer Go to this website: http://www.cancer.gov/ , click on “Prevention, Genetics, Causes” under the heading “Cancer Topics”, click on “Cancer Prevention”, and then click on “Cancer Trends Progress Report: Prevention”. List strategies that can reduce your risk of cancer.

V. Another Type of Cell Division

A. Meiosis – cell division that produces the reproductive cells that give rise to succeeding generations. Cell division of germ-line cells which are called oogonia (cells that produce eggs) and spermatogonia (cells that produce sperm). Eggs and sperm are also called gametes.

Watch Amoeba Sisters Meiosis

1. Gametes fuse to make a zygote (embryo) which grows into a whole organism.

2. Each human body (somatic) cell has 23 pairs of

chromosomes or 46 chromosomes. If an egg and sperm each brought 46 chromosomes to their union, the result would be a zygote with 92 chromosomes, the next would have 184, the next would be 368 and so on.

B. How do chromosomes avoid the problem of doubling

with each generation? 1. Haploid (n) 2. Diploid (2n) Meiosis now means: C. Phases of Meiosis:

1. First Meiotic Division (Meiosis I)

Page 6: Cell Division & Reproduction (Ch. 6)

2. Second Meiotic Division (Meiosis II)

Steps in Meiosis I:

Crossing Over Independent Assortment Now each cell divides again because cells still have duplicated chromosomes.

Diploid Spermatogonia or Oogonia

Page 7: Cell Division & Reproduction (Ch. 6)

Steps in Meiosis II:

Meiosis produces haploid germ line cells (egg and sperm = gametes) for producing another individual! Watch course website animations on Meiosis and Meiosis Bioflix Animation D. Gamete Formation (Gametogenesis) in Humans Read about sperm formation (spermatogenesis) in males and answer the following:

1. What organ are spermatozoa (sperm) formed in?

2. What basic cells produce sperm and from what you learned from our lecture on meiosis are these basic cells haploid or diploid?

3. How long can males produce sperm?

Spermatogonia produce sperm cells as well as more spermatogonia, which means they not only produce sperm but more sperm factories as well. This self-generating ability qualifies them as stem cells and is why males can produce sperm for so long.

Read about oocyte (egg) formation (Oogenesis) in females and answer the following: 1. What organ are ova (eggs) formed in?

2. What basic cells produce eggs and from what you learned from our lecture on meiosis are these basic cells

haploid or diploid?

Haploid Sperm or eggs

Haploid

Page 8: Cell Division & Reproduction (Ch. 6)

3. When are oocytes (eggs) produced in large numbers in females? Before or after birth? So were you still a fetus when all of your eggs were produced? 4. From what you learned from the previous questions, do you think adult females have reproductive stem

cells like males?

A female’s eggs begin Meiosis I before birth and then remain halted in Meiosis I and dormant in the ovaries until ovulation occurs. During ovulation, Meiosis I is completed and is then halted in Meiosis II. Once fertilization with a sperm occurs, Meiosis II is completed. So, most eggs will remain in Meiosis I for years. This long duration of meiotic division may account for the high frequency of meiotic errors such as nondisjunction.

Read “Study Suggests Way To Create New Eggs In Women” Remember, science is constantly seeking new evidence and is always open to question and revision!

E. Why Meiosis is Important 1. Is the chromosome duplication problem solved? 2. Meiosis provides two sources of genetic variation (ways for genetic diversity to exist among organisms)

a. How many configurations of chromosomes can occur? - How many sides can they line up on?

- How many chromosomes in a gamete?

- ____________________ possible line up configurations can occur! If you had 8.4 million eggs or sperm, each one would be slightly different from each other!

- How likely is it that the egg that produced you will have the same line up configuration as the egg

that produced your sibling?

- How many possible chromosome combinations are there when an egg and sperm unite during fertilization?

- This means that if one couple was to have 64 trillion babies, each baby would be genetically different. Remember genes on these chromosomes code for eye color, hair color, height, etc. Now that’s a lot of genetic and physical variation!

- The shuffling of genetic material that occurs during meiosis and random fertilization are the reasons why children look different from their parents and from each other!

b. What else is this diversity responsible for?

Page 9: Cell Division & Reproduction (Ch. 6)

Meiosis

3. Important in sex determination a. Individuals with one X and one Y are ___________ and those with two Xs

are _____________. b. Human males and females both have 44 autosomes (chromosomes other

than sex chromosomes). Because of meiosis, each gamete (egg or sperm) contains one sex chromosome and a haploid set of autosomes (22 in humans).

c. All eggs contain a single X chromosome; half of sperm cells will contain X and other half will contain Y.

d. Which parent determines the sex of a child? E. When Meiosis Goes Wrong 1. Nondisjunction

a. Aneuploidy 2. Conditions caused by nondisjunction: a. Individual may not have the standard number of autosomes. Example? b. Individual may not have the standard number of sex chromosomes. Example? Sex Chromosome Abnormalities: - Turner syndrome = XO (only 45 chromosomes instead of 46); female hormone deficiencies at puberty; can be t - Trisomy = XXX; most have no detectable defects; still fertile

Page 10: Cell Division & Reproduction (Ch. 6)

3. Mistakes in cell division can lead to new species. Polyploidy – when one or more entire sets of chromosomes have been added a. At least half of all flowering plants are polyploid b. In plants, if meiosis fails to occur in reproductive organs and gametes are produced by mitosis the

gametes will be diploid (2n) and will produce a tetraploid (4n) offspring and may develop into a mature tetrploid plant that can reproduce by self-fertilization. The tetraploid plants will make up a new species in just one generation.

F. Read about “PGD” and answer the following: 1. State what “PGD” stands for and briefly summarize how this process is done.

2. Who can benefit from PGD?

3. State two ethical issues/concerns surrounding PGD.

VI. Reproduction of Organisms Watch Amoeba Sisters Asexual and Sexual Reproduction A. Asexual Reproduction Examples? B. Sexual Reproduction Examples?

Advantages and disadvantages of each type?

Page 11: Cell Division & Reproduction (Ch. 6)

VII. Mitosis vs. Meiosis Mitosis Meiosis What type of cells is produced from this type of cell division?

Is the cell haploid or diploid before cell division?

Is the cell that is produced after cell division haploid or diploid?

Will this type of cell division produce exact copies of or genetically different cells?

Why is this type of cell division needed by organisms?

Page 12: Cell Division & Reproduction (Ch. 6)

Biotechnology (Ch. 5) Biotechnology I. Transgenic Biotechnology A. Transgenic organism – an organism whose genome has

incorporated one or more genes from another species B. Recombinant DNA – segments of DNA that have been

combined into a sequence that does not exist in nature C. Examples of this technology

1. Transgenic Microbes & Cells

2. Transgenic Livestock 3. Transgenic crops (genetically modified crops)

Watch this video to learn more about Genetically Modified Foods and its history.

Read the articles “The Risks on the Table” and “Are Engineered Foods Evil?” and answer the following: 1. Describe three specific concerns surrounding genetically modified foods (GMFs). 2. Describe three specific benefits of genetically modified foods (GMFs).

Page 13: Cell Division & Reproduction (Ch. 6)

Read the article “Are Engineered Foods Evil?” and this article on genetically modified organisms (GMOs) and answer the following: 1. According to the majority of the latest research, are GMFs/GMOs safe to consume?

2. Are they safe for the environment? How so?

Different cells with specific functions contain a complete set of DNA which means that cells have the potential to act like every other cell if its pattern of gene expression is altered. II. Cloning & Stem Cells Watch Amoeba Sisters How Cells Become Specialized A. Reproductive Cloning 1. What is the goal of this type of cloning?

2. Advantages & disadvantages of reproductive cloning? B. Therapeutic Cloning

1. What is the goal of this type of cloning?

2. Embryonic stem cells – cells in an early animal embryo that have not specialized yet. They will specialize during development to give rise to all cell types in the body

a. When grown in lab can divide indefinitely and can be induced to specialize into a particular cell type.

3. Adult stem cells – partly specialized cells found in an adult’s body that constantly divide and produce new cells (i.e. skin cells, cells in bone marrow that produce blood cells, etc.)

4. Advantages & disadvantages of stem cell research?

Page 14: Cell Division & Reproduction (Ch. 6)

Watch the video “Stem Cells Breakthrough” and answer the following questions: 1. Why are embryonic stem cells also called pluripotent cells? 2. What type of adult cell have scientists been able to turn into embryonic stem cells? 3. Is it true that virtually all cells in the body have the same DNA? 4. What happens to our genes during embryonic development which leads to the production of different cell types? 5. What needs to be done to the genes in a skin cell to turn it back into an embryonic stem cell? 6. What are these induced stem cells called? Watch the video “Anthony Atala on growing new organs” and answer the following questions:

1. What organ was the first to be transplanted in humans? 2. How often does a patient die from diseases that could be treated with tissue replacement?

3. How often do your bones regenerate?

Your skin? 4. Briefly describe the method used on donor organs, like the liver, to engineer them for patient use.

Page 15: Cell Division & Reproduction (Ch. 6)

Watch the video “Replacing Body Parts” and answering the following: When you wash the cells off of an organ, what is left? What was the chemical that was eventually found to successfully strip the heart of its cells but leave the scaffold intact? What are two benefits of using this scaffold based organ technology over conventionally used organ donation methods? Watch this video “Anthony Atala: Printing a Human Kidney” to learn more on regenerative medicine. Read the article “Whose Blood Is It, Anyway?” and answer the following: 1. Describe two advantages and two disadvantages of using umbilical cord stem cells instead of bone marrow

transplants for treating people with immune system and enzyme deficiencies, sickle cell anemia, leukemia, and other cancers.

III. Forensic Biotechnology A. DNA Fingerprinting (Profiling) Steps in DNA fingerprinting: 1. DNA is amplified using Polymerase Chain Reaction (PCR) What does PCR create?

Page 16: Cell Division & Reproduction (Ch. 6)

2. DNA is cut into fragments using restriction enzymes a. Restriction enzymes – always cut DNA at certain

locations b. In this example, where does this specific restriction

enzyme always cut?

3. DNA fragments are compared using gel

electrophoresis

a. What two factors cause DNA segments to separate out on a gel?

4. Can then determine if samples are the same DNA or

different

Page 17: Cell Division & Reproduction (Ch. 6)

Genetics (Ch. 7) I. Genetics A. Father of Genetics: Gregor Mendel – Austrian monk living in Czech

Republic monastary (mid 1800’s) - First to develop a set of principles that explain inheritance and

that inheritance of many genetic characteristics follows a few simple rules.

B. Mendel’s subjects: pea plants C. How to read a Punnett Square 1. What is the P generation? 2. What is the F1 generation? 3. What must Parents undergo to produce haploid gametes? 4. Phenotype 5. Genotype 6. Does genotype largely determine phenotype? D. Monohybrid (One-Trait) Crosses Watch Amoeba Sisters Monohybrids and the Punnett Square Guinea Pigs 1. Started with parent plant that produced yellow peas (YY) and one that produced green peas (yy) and crossed fertilized them. 2. Their offspring (F1 generation) were all yellow (Yy). 3. Was the heritable factor green lost? 4. Crossed fertilized the F1 generation 5. Their offspring (F2 generation) were ¾ yellow and ¼ green (3:1 ratio) 6. Conclusions: a. How many forms of genes (alleles) does each individual have for each trait? b. How does an individual get these genes (alleles)? c. How many alleles for each trait does each gamete (sperm or egg) contain? d. What must the alleles do in order to only have one allele for each trait in each gamete? e. How many alleles for each trait are present in the embryo when fertilization occurs (the union of sperm and egg)?

Page 18: Cell Division & Reproduction (Ch. 6)

7. Mendel’s Law of Separation (Segregation): Pairs of alleles separate during gamete (egg & sperm) formation (meiosis) and the fusion of gametes at fertilization creates allele pairs again. 8. What do we call an allele when it masks the expression of the other allele? 9. What do we call an allele whose trait is being masked? E. Alleles on Homologous Chromosomes 1. Homozygous

2. Heterozygous F. More Monohybrid Crosses Phenotypic ratio? Genotypic ratio?

1. Now cross fertilize the F1 generation:

Phenotypic ratio?

Genotypic ratio?

F1 Generation

Eggs Sperm

X F1 Generation

Tall Short

Page 19: Cell Division & Reproduction (Ch. 6)

Phenotypic ratio?

Genotypic ratio? Now cross fertilize the F1 generation: Phenotypic ratio? Genotypic ratio? G. Dihybrid Two-Trait Crosses Watch Amoeba Sisters Two-Trait and Dihybrid Crosses 1. Crossed homozygous smooth and yellow pea plants (SSYY) with

wrinkled and green pea plants (ssyy) 2. Offspring all were smooth and yellow (SsYy) = heterozygotes

3. Mendel wondered if the two traits (SY) or (sy) were transmitted from parents to offspring as a package or if each trait was inherited independently of the other.

4. So he crossed fertilized the F1 generation 5. The F2 generation exhibited 4 phenotypes in a ratio of 9:3:3:1 6. Conclusions:

a. Do all possible combinations of traits occur in the gametes?

b. Does each pair of traits separate independently of the other pairs? 7. Mendel’s Law of Independent Assortment: Each pair of alleles separates

independently of the other pairs during gamete formation (metaphase in meiosis). The inheritance of one characteristic has no effect on the inheritance of another.

F1 Generation

F2 Generation

PP pp

Page 20: Cell Division & Reproduction (Ch. 6)

Phenotypic ratio? Genotypic ratio? Now cross fertilize the F1 generation: Phenotypic ratio? Genotypic ratio?

F1 Generation

F2 Generation

Tall & Green pods

Short & Yellow pods

Page 21: Cell Division & Reproduction (Ch. 6)

Phenotypic ratio? Genotypic ratio? Now cross fertilize the F1 generation: Phenotypic ratio? Genotypic ratio?

Round & Yellow peas Wrinkled and Green peas

P Generation

F1 Generation

F2 Generation

Page 22: Cell Division & Reproduction (Ch. 6)

H. Human Disorders Controlled by a Single Gene - These disorders show inheritance patterns that Mendel studied.

- Genes involved in these disorders are located on autosomes.

1. Autosomal Recessive Disorders a. Ex. Deafness

Parents are heterozygous & are carriers of recessive allele for disorder but are phenotypically normal.

Can they produce a child that exhibits the condition?

What is the probability of this happening?

b. Ex. Sickle-Cell Anemia:

a. Hemoglobin (protein) in red blood cells carry oxygen to body. Sickle shaped red blood cells have a different form of hemoglobin, they clog vessels and result in tissue damage.

Page 23: Cell Division & Reproduction (Ch. 6)

b. Widely affects Africa. 1 in 500 African Americans born in U.S. is homozygous. 1 in 10 African Americans is heterozygous.

2. Autosomal Dominant Disorders

a. Parent need only pass on a single allele for offspring to suffer from condition.

b. Usually individuals with this disorder are

heterozygous (Hh) for the disorder. Those that are homozygous for the disorder (HH) die while still an embryo.

c. Shows that dominant allele is not always

‘better’ or more abundant than the recessive! d. Ex. Huntington disease

I. Mendel’s Principles and Human Inheritance Watch Amoeba Sisters Pedigree

a. Mendel’s principles apply to the inheritance of some human traits, not all. Traits such as eye, hair, and skin color do not follow Mendel’s principles.

b. Pedigrees are used to determine inheritance of characteristics that follow Mendel’s principles in humans.

d

?

?

d

d

?

Page 24: Cell Division & Reproduction (Ch. 6)

J. Mendel’s principles are not valid for all traits: Watch Amoeba Sisters Incomplete Dominance,

Codominance, Polygenic Traits, and Epistasis! 1. Incomplete Dominance

Heterozygote phenotype is intermediate between

either of the homozygous phenotypes.

a. Ex. Snapdragon flowers: - R allele produces red - r allele produces no pigment - Rr produces?

2. Multiple Alleles, Codominance, & Blood Type

Watch Amoeba Sisters Multiple Alleles (ABO Blood Types) and Punnett Square a. Multiple Alleles - Each individual carries, at most, two different

alleles for a particular gene, however, more than two possible alleles exist in population

- Ex. Human blood types (Table 11.3): there are 3

alleles for blood type A, B & O which can produce 4 phenotypes (A, B, O or AB)

- These letters refer to carbohydrates designated A

& B which may be found on surface of red blood cells. A person’s red blood cells may be coated with one substance or the other (type A or B), with both (type AB), or with neither (type O). Matching compatible blood groups is critical for blood transfusions. If donor’s blood has foreign carbohydrate on surface of cells, antibodies in recipient’s blood bind to the foreign carb and causes clumping.

Page 25: Cell Division & Reproduction (Ch. 6)

b. Codominance

What alleles are both dominant?

3. Polygenic Inheritance

a. Most traits are controlled by many genes. b. Height, weight, eye color, skin color are controlled by several genes

working together. c. That’s why we see a range of specific traits and not only really tall

people and really short people, or only really dark and really light characters.

d. Causes greater diversity!

II. Sex Chromosomes & Sex Linked Genes Watch Amoeba Sisters Punnett Squares and Sex-Linked Traits A. Sex linked genes 1. Eye color in fruit flies a. White eye color is a recessive trait whose gene is on the X chromosome b. Female can carry one allele for white eye and one for red allele on her

second X chromosome. c. Male will be white eyed if only one of his chromosomes, his lone X

chromosome, carries an allele for white eyes d. How would a female get white eyes?

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2. Sex linked disorders in humans: hemophilia (failure of blood to clot properly), Duchene muscular dystrophy, red-green color blindness

a. Is color blindness on the X or Y

chromosome? b. Is color blindness a dominant or recessive?

c. Which child will be color blind? d. How would a daughter be color blind? III. Genes & Environment A. Effects of genes vary according to the environment in which genes

are expressed. An organism’s genotype and environment interact to produce an organism’s phenotype.

Watch the online video “Epigenetics” and answer the following questions:

1. Using computer terms describe what one’s epigenome is compared to one’s genome.

2. What does our epigenome “tell” our cells to do? 3. Does age affect how similar the epigenomes of identical twins are? How so? 4. Describe what epigenetic therapy is and how it works and state what illness it is being used to treat. 5. Can we negatively alter our epigenomes and our children’s epigenomes? How so?

Xn XN

XN