Genetics Exam 5/ Comprehensive Final

Clonal evolution:

Cancer arises by successive mutations in a clone of proliferating cells

CDKs mediate the transition from the

G1-toS phase in human cells

Which cell cycle phases contain critical DNA damage checkpoints? G2G2 G1G1 M G0

G2G2 G1G1 M

The RAS oncogene is the mutant form of the RAS proto-oncogene -

Normal RAS is inactive until it becomes activated by binding of growth factors to their receptors - oncogenic forms of RAS are constitutively activated

Cancer mutagens occur in 2 forms:

Oncogenes - dominant (gain of function) mutations that promote cell division. The wild-type form of oncogenes are proto-oncogenes (for example, Ras, myC) Mutated tumor-suppressor genes - recessive mutations. fail to slow or control the cell cycle. The wild-type form is tumor-suppressor gene (for example, retinoblastoma)

Base excision repair

Starts with Glycosylase removing the wrong base from the deoxyribose

Reproductive cloning

The purpose of reproductive cloning is to create a genetically identical organism (twins).

Biotechnology:

The use of living systems and organisms to develop or make industrial, food, or pharmaceutical products

Pluripotent cells

can differentiate into almost every cell, but can't give rise to an entire, intact individual

Multipotent cells

can differentiate into several cell types

Xeroderma pigmentosum

extreme sensitivity to UV light 200x higher rate of skin cancer

The blastocyst is the most valuable source of embryonic stem cells - the problem is

is has to be destroyed in the process of harvesting stem cells

Many cancer cells are immortal because they have mutations that allow telomerase to be constitutively expressed, allowing cancer cells to divide indefinitely. How might this knowledge be used to design an anticancer drug? - A drug can be designed to enhance telomerase activity in healthy cells to outcompete cancerous ones. - A drug can be designed to reduce all telomerase activity in cells, preventing indefinite cell division from ever occurring. - A drug can be designed to target and inhibit the telomerase activity in cancer cells, reducing the ability of cancer cells to divide indefinitely. - A drug can be designed to inhibit DNA repair mechanisms, thereby shortening the telomeres of cancer cells.

- A drug can be designed to target and inhibit the telomerase activity in cancer cells, reducing the ability of cancer cells to divide indefinitely.

Why are embryonic stem cells thought to have more therapeutic potential than adult, or somatic, stem cells? - Adult stem cells are less specialized when extracted for therapy, whereas embryonic stem cells are more specialized - Adult stem cells differentiate into only one or few cell types, whereas embryonic stem cells can differentiate into nearly any cell type - Adult stem cells are capable of only a limited number of divisions, whereas embryonic stem cells are capable of dividing infinitely - Adult stem cells are difficult to culture in a laboratory setting, whereas embryonic stem cells are easily cultured in a laboratory setting

- Adult stem cells differentiate into only one or few cell types, whereas embryonic stem cells can differentiate into nearly any cell type

Changes that produce a potential for immortality

- loss of limitations on the number of cell divisions - ability to grow in culture - normal cells do not grow well in culture - restoration of telomerase activity

DNA repair mechanisms

-proofreading - Direct DNA repair mechanisms - Base excision repair, starts with DNA-glycosylases - Nucleotide excision repair, starts with excision of nucleotides (UVR system) - Methyl-directed mismatch repair

Nucleotide excision repair

13 nucleotides are excised from DNA

What type of signals subvert the normal regulation of the cell cycle surrounding tissues? A. Paracrine signals B. Endocrine signals C. Autocrine signals

C. Autocrine signals

External factors: How do the cells know when to divide? What control the synthesis of cyclins in a cell?

Cells communicate with one another through signaling: contact dependent or cell-bound signals - signal transducers relay messages and transcription factors activate expression of genes

Place the events that control the progression of cells through the G1/S checkpoint of the cell cycle in order. Cyclin- CDK complexes phosphorylate RB proteins Inactivated RB releases active E2F protein Cyclins D & E bind CDK proteins E2F transcribes genes required for DNA replication

Cyclins D & E bind CDK proteins Cyclin- CDK complexes phosphorylate RB proteins Inactivated RB releases active E2F protein E2F transcribes genes required for DNA replication

In order for a cell to turn cancerous, both alleles of a proto-oncogene must be mutated True or false?

False

True or False A mutated retinoblastoma allele acts as a dominant oncogene, because if a patient inherits a single mutated allele, he or she will soon develop cancer of the retina

False

Early childhood experience leaves epigenetic marks -

Neglect during early days in life leads to methylation of the glucocorticoid receptor gene and leads to fearfulness and anxiety in adulthood

Proofreading:

The 3' - 5' exonuclease activity of DNA polymerase. Reduces DNA polymerase error rate from 10E-5 to 10E-7

Cancer is the failure of the cell cycle.

The regulation of the cell cycle is under the control of the surrounding cells/tissues Cancer occurs when a cell does not obey "instructions" from surrounding cells. A cell ignores instructions from surrounding tissues when it accumulates several mutations in genes that are involved in its signaling system or cell cycle control system Cancerous tumors are always clones that derive from a single somatic cell that accumulated the critical assortment of mutations

Classify the descriptions of stem cells as totipotent, pluripotent, or multipotent. - Can become all cells in the body, including extraembryonic cells - Can only become different cell types within a tissue type - Can become all cells in the body, but not extraembryonic cells - An example is embryonic stem cells - An example is adult stem cells - Can develop into a new organism - An example is a zygote

Totipotent: - Can become all cells in the body, including extraembryonic cells - Can develop into a new organism - An example is a zygote Pluripotent: - Can become all cells in the body, but not extraembryonic cells - An example is embryonic stem cells Multipotent: - An example is adult stem cells - Can only become different cell types within a tissue type

True or false? Epigenetic modification of chromatin can be modulated by RNA molecules

True

True or false? The environment in which an organism lives influences its chromatin structure and the expression of its genes

True

Dutch Hunger Winter (1944-1945)

Women were exposed to famine at different stages of pregnancy The effects on fetuses later in life: Early gestation - heart disease, elevated lipid levels, obesity Late gestation - decreased glucose tolerance

Methyl-directed mismatch repair

a base pair mismatch is detected, and a strand of surrounding DNA is removed and replaced Adenine methylase tags A residues in GATC sites. At mis-paired nucleotides, MutS and MutL detect mismatch MutL recuits, MutH nicks the strand that is opposite to the methyl group- tagged GATC site

Signal transduction -

activation and inhibition of intracellular targets after growth factor to receptor

Cell differentiation is mediated

at the epigenetic level

Unipotent cells

can only differentiate into one cell type

Loss of gap junctions

cancer cells lose channels for communicating with adjacent cells

The incident of most cancers shows a dramatic increase with age - this is because

cancer requires the accumulation of several mutations, the chance of which increase as the cells get older

The normal progression of the cell cycle is regulated by

cyclins and cyclin-dependent kinases (CDKs): - the G1-to-S phase transition is regulated by the G1 Cyclin/CDK complex - the G2-to-M phase transition is regulated by the mitotic cyclin/CDK complex

Cancer can be caused by mutations that

improperly inactivate tumor suppressor genes -Function of normal allele of tumor suppressor genes is to control cell proliferation - If they are inactivated by mutation, it becomes more likely that cancer will occur - Mutant tumor suppressor alleles act recessively and cause increased cell proliferation - Tumor suppressor genes identified through genetic analysis of families with inherited predisposition to cancer - inheritance of a mutant tumor suppressor allele - one normal allele sufficient for normal cell proliferation in heterozygous - wild-type allele in somatic cells of heterozygote can be lost or mutated > abnormal cell proliferation

Loss of contact inhibition

lost property to stop dividing when contacted by another cell

Tumor-suppressor genes typically act in a ___________ manner, and oncogenes typically act in a ______________ manner.

recessive dominant

Loss of cell death

resistance to programmed cell death

Cancer occurs when

the control mechanism that regulates cell division malfunctions

Genomic imprinting: an example of

the conversion of euchromatin to heterchromatin

What are checkpoints? - control points on protein synthesis that limit cancerous growth - transition points during the process of chromosome separation that allow cell division to begin - transition points during the cell cycle that ensure all cellular components are functioning properly - transition points during the process of DNA replication that allow cell division to begin - periods of growth and development between cell divisions

transition points during the cell cycle that ensure all cellular components are functioning properly

Autocrine stimulation

tumor cells make their own signals to divide

How does an epigenetic change differ from a mutation? - A mutation alters the nucleotide sequence in DNA. An epigenetic change does not alter the DNA sequence, but can be inherited by daughter cells. - Epigenetic changes occur due to environmental effects and only persist as long as the environment that induced them remains constant. Mutations are permanent. - A mutation is heritable. Epigenetic changes affect only the cells in which they occur during that cell's lifetime. - Mutations involve nucleotide sequences of only one or a few base pairs. An epigenetic change involves large regions of a chromosome, thousands of base pairs or more in length.

- A mutation alters the nucleotide sequence in DNA. An epigenetic change does not alter the DNA sequence, but can be inherited by daughter cells.

Select the events that are a consequence of activating mutations in the ras gene. - Abnormally rapid cell growth and proliferation is induced. - Specific transcription factors are activated by phosphorylation. - The ras proto-oncogene is converted into an oncogene. - Malignant transformation of normal cells is inhibited. - The signal transduction cascade of the MAP kinases is repressed.

- Abnormally rapid cell growth and proliferation is induced. - Specific transcription factors are activated by phosphorylation. - The ras proto-oncogene is converted into an oncogene.

Study of Oncogenes:

- Exposure of noncancerous cells to tumor DNA in culture - human tumor DNA to transform normal mouse cells - human DNA isolated from transformants - Another approach to identifying oncogenes is analysis of tumor causing retroviruses

Select the scenarios that are likely due to epigenetic modifications. - A mother with a mutation in the BRCA1 gene wants her son and daughter tested. The mother inherited the mutation from her father. The son develops prostate cancer, despite inheriting the mutation from his mother. The daughter did not inherit the mutation and does not develop cancer. - A large population of lizards inhabiting an island have red or yellow colored skin. When red lizards mate with yellow lizards, the resulting offspring are mostly red, with some yellow. A hurricane wipes out most of the population, and the next seven generations of lizards are all red. - Female rats exposed to dioxin, a toxin, during pregnancy have offspring with a high rate of kidney disease. Females from the first generation who were not directly exposed to the toxin during pregnancy also have offspring with disease. This pattern continues for three generations. - During development, undifferentiated stem cells with the potential to develop into any cell type have many regions of heterochromatin, in which genes associated with differentiation are silent. The chromatin is reconfigured when cells differentiate, and these regions become euchromatin. - In mice, methylation of an allele of the agouti gene locus determines coat color. When methylated, the coat is brown, and when unmethylated, the coat is yellow. Pregnant yellow female mice are fed a diet rich in methyl groups and have offspring with brown coats. - A female Siberian Husky is the only dog in its litter to be born with two differently colored eyes: blue and brown. Its mother also has one blue eye and one brown eye, whereas its father has two brown eyes.

- Female rats exposed to dioxin, a toxin, during pregnancy have offspring with a high rate of kidney disease. Females from the first generation who were not directly exposed to the toxin during pregnancy also have offspring with disease. This pattern continues for three generations. - During development, undifferentiated stem cells with the potential to develop into any cell type have many regions of heterochromatin, in which genes associated with differentiation are silent. The chromatin is reconfigured when cells differentiate, and these regions become euchromatin. - In mice, methylation of an allele of the agouti gene locus determines coat color. When methylated, the coat is brown, and when unmethylated, the coat is yellow. Pregnant yellow female mice are fed a diet rich in methyl groups and have offspring with brown coats.

Somatic cells can be reprogrammed to pluripotent stem cells in two different ways;

- Induced pluripotent stem cells (iPSC) - somatic cells are converted to iPSCs by the expression of four transcription factors (Oct4, Klf4, Sox2, c-Myc), key regulators of cell differentiation - Nuclear transfer embryonic stem cells (NT-ESC) - a nucleus from a differentiated somatic cell is transferred to an egg cell from which the haploid nucleus has been removed

Li-Fraumeni Syndrome, or LFS, is an inherited cancer disorder that is caused by heterozygous mutations in the p53 gene. LFS patients are highly prone to bone, muscle, blood, adrenal glands, and brain cancers. Select the mechanism that explains the development of different types of cancers in LFS patients with mutations in thep53 gene. - Mutations in p53 are observed only in the organs that develop cancer. - Mutations in p53 affect checkpoint response in all cells of the body. - Heterozygous mutations in p53 constitutively activate the targets of p53. - Only some of the tissues constitutively activate the p53 pathway. - The G1/S phase checkpoint is unaffected in some of the tissues.

- Mutations in p53 affect checkpoint response in all cells of the body.

Assume that the provirus in the figure inserts just upstream of a tumor‑suppressor gene. Would this likely cause cancer? Why or why not? - Yes, the provirus is likely to cause the gene to be duplicated multiple times so that the tumor‑suppressor gene will be overexpressed. - No, the provirus has a weak promoter and likely will prevent the normal expression of the tumor‑suppressor gene. - Yes, the provirus produces a gene product that will likely result in some type of epigenetic change. - Yes, the provirus likely has a strong promoter that will lead to an over‑expression of the tumor‑suppressor gene. - No, the provirus likely has a stronger promoter that will cause the over‑expression of the tumor‑suppressor gene.

- No, the provirus likely has a stronger promoter that will cause the over‑expression of the tumor‑suppressor gene.

Select the best example of transgenerational epigenetic inheritance. - Individuals with a history of childhood abuse have more methylation of the glucocorticoid receptor gene than individuals without such history. - A long non‑coding RNA transcribed from the Xist gene suppresses transcription of one X chromosome in each female mammal cell. - Vinclozolin binds to insulin receptors, disrupting glucose metabolism and causing epigenetic methylation of the insulin receptor gene. - Offspring of rats with high‑fat diets were fed a low‑fat diet and had normal weights, but still developed symptoms of diabetes. - Experimental rats with nutrient‑restricted diets were at greater risk of infection than control rats that were fed a nutritionally‑complete diet.

- Offspring of rats with high‑fat diets were fed a low‑fat diet and had normal weights, but still developed symptoms of diabetes.

Oncogenes and their effects on cell division;

- Oncogenes promote cell growth - In eukaryotes, the cell cycle is regulated in part by polypeptide hormones known as growth factors - Growth factors bind to cell surface receptors and initiate a cascade of cellular events leading ultimately to cell division - Epidermal growth factor (EGF) is a growth hormone - the function of the normal Ras protein

Certain behavioral traits in humans are believed to be encoded by the X chromosome. Examples of such traits include verbal ability and seeking social interactions. For these traits, research has shown that there is less variability between identical male twins than between identical female twins. Which phenomenon best explains these results? - Females have double the amount of X expression so there's more room for error. - Males have a Y chromosome, which is much smaller than the X. - Male twins both get the same mitochondria from their mother. - One X chromosome is randomly inactivated in females.

- One X chromosome is randomly inactivated in females.

One method to clone a mammal involves nuclear transfer, in which a somatic cell nucleus from a donor mammal is transferred to a recipient egg cell with its nucleus removed. This method results in few live births overall due to a high prevalence of developmental abnormalities. Notably, the probability of a live birth is significantly greater for embryos cloned from the nuclei of undifferentiated embryonic stem cells than for embryos cloned from the nuclei of differentiated somatic cells (Rideout et al., 2001). Select the best explanation of why embryos cloned from undifferentiated embryonic stem cells have greater developmental success than embryos cloned from differentiated somatic cells. - Embryos not formed from the fusion of a sperm and egg lack genomic imprinting, which increases the likelihood of abnormal embryonic development. - Patterns of epigenetic markers are different in stem cells and somatic cells, with stem cells having epigenetic patterns more closely associated with early development. - Long non‑coding RNA transfers with the donor nucleus, which represses expression of autosomal genes important to embryonic development. - Patterns of epigenetic markers in stem cells and somatic cells are identical, indicating that the observed difference is not due to epigenetic regulation of development. - Somatic cells are older than stem cells and have accumulated mutations that disrupt normal embryonic development.

- Patterns of epigenetic markers are different in stem cells and somatic cells, with stem cells having epigenetic patterns more closely associated with early development.

Place the steps of DNA methylation maintenance in order from first to last: - Any unmethylated DNA is methylated - The replicated DNA strand is synthesized unmethylated - Fully methylated DNA is produced - Methyltransferase binds to DNA methyl groups - Prior to replication, CpGs are fully methylated

- Prior to replication, CpGs are fully methylated - The replicated DNA strand is synthesized unmethylated - Methyltransferase binds to DNA methyl groups - Any unmethylated DNA is methylated - Fully methylated DNA is produced

How do scientists use twin and adoption studies in the study of human behavioral genetics? - Scientists compare sets of monozygotic and dizygotic twins. If dizygotic twins are more likely to exhibit the same behaviors than monozygotic twins, the behavior probably has a strong genetic component. - Scientists compare sets of siblings and twins raised in the same household and those raised by adoptive families. If the adopted individuals are more likely to share behavioral traits with their biological parents than with their adoptive parents, the behavior probably has a strong genetic component. - Scientists compare sets of monozygotic and dizygotic twins. If monozygotic twins are more likely to exhibit the same behaviors than dizygotic twins, the behavior probably has a strong genetic component. - Scientists compare children that have been adopted with children raised by their biological parents. If those that have been adopted are more likely to display a rare behavior than those that were raised by their biological parents, the trait probably does not have a strong genetic component. - Scientists compare behaviors in monozygotic twins separated at birth. If they are more likely to display the same behaviors than unrelated individuals of the same age, the behavior probably has a strong genetic component.

- Scientists compare sets of siblings and twins raised in the same household and those raised by adoptive families. If the adopted individuals are more likely to share behavioral traits with their biological parents than with their adoptive parents, the behavior probably has a strong genetic component. - Scientists compare sets of monozygotic and dizygotic twins. If monozygotic twins are more likely to exhibit the same behaviors than dizygotic twins, the behavior probably has a strong genetic component. - Scientists compare behaviors in monozygotic twins separated at birth. If they are more likely to display the same behaviors than unrelated individuals of the same age, the behavior probably has a strong genetic component.

Suppose Nicole recently learned that she inherited a mutant RB1 allele from her mother, who had retinoblastoma. RB1 is a tumor suppressor gene that is related to retinoblastoma. Why would Nicole be at higher risk for getting retinoblastoma at an earlier age than her sister, Tiffany, who inherited a normal RB1 allele from their mother? - If an individual has even one mutation in a tumor suppressor gene, cancer will not be suppressed. - An individual who inherited two functional alleles of a tumor suppressor gene is less likely to eat highly carcinogenic foods. - Someone with one mutant allele in a tumor suppressor gene only requires a mutation in the one remaining normal allele for tumors to form. - One mutant allele of a tumor suppressor gene increases the likelihood that the wild-type allele will also mutate.

- Someone with one mutant allele in a tumor suppressor gene only requires a mutation in the one remaining normal allele for tumors to form.

Select the main reason that stem cells are considered valuable for research applications. - Stem cells differentiate into other cell types but do not self‑renew. - Stem cells self‑renew but do not differentiate into other cell types. - All stem cells are pluripotent. - Stem cells can regenerate the damaged section of an organ. - Embryonic stem cells only give rise to specific cell types.

- Stem cells can regenerate the damaged section of an organ.

Stem cells:

- Stem cells supply the cells that construct our bodies from a fertilized egg - in the adult, stem cells also replenish damaged cells - Stem cells have two common characteristics - 1. they have the capacity to divide -2. they have the capacity to differentiate into one or more specialized cell types

Prader-Willi and Angelman syndromes

- The epigenetic, sex-specific gene silencing associated. with imprinting is dramatically evident in Prader-Willi syndrome and Angelman syndrome characterized by neuromuscular defects, mental retardation, and other abnormalities

Tumor-suppressor genes and their effects on cell division:

- The first identification of a human tumor-suppressor gene involved studies of retinoblastoma - a tumor of the retina of the eye - There are two types of retinoblastoma - 1. inherited, which occurs in the first few years of life 2. Non-inherited, which occurs later in life

A genetic counselor determines that patients with a deletion in a particular region of a chromosome are more likely to develop cancer than other people. Is the gene responsible for the increased risk of cancer a tumor suppressor or a proto-oncogene? - The gene is a tumor suppressor, because tumor suppressor genes allow the cell to enter into S phase. - The gene is a tumor suppressor, because tumor suppressor genes induce apoptosis in abnormal cells. - The gene is a proto-oncogene, because proto-oncogenes promote cell division at appropriate times. - The gene is a proto-oncogene, because proto-oncogenes regulate mitotic checkpoints.

- The gene is a tumor suppressor, because tumor suppressor genes induce apoptosis in abnormal cells.

Genomic imprinting occurs when gene expression in the offspring depends upon whether a particular allele was inherited from the mother or the father. Which statement is likely to explain the evolutionary basis for the existence of imprinting? - The ideal reproductive strategy is different for males and females. For example, maximum birth weight and fetal growth are favored by fathers because they increase offspring survival. Mothers favor maternal survival and the preservation of resources for future reproduction. Therefore, a mother may benefit from reduced fetal growth rates. - Strong maternal attachment is favored in mothers, and strong paternal attachment is favored in fathers. Therefore, offspring that inherit a gene for paternal attachment from their mother will not express the gene. Likewise, offspring that inherit a gene for maternal attachment from their father will not express the gene. - Sex-linked traits are more likely to affect males than females. Therefore, if a trait is beneficial, it may be expressed only when inherited from the father. Both beneficial and harmful traits may be expressed when inherited from the mother. - Different characteristics increase reproductive success for males and females. For example, a deep voice decreases a human female's chances of finding a mate, but does not harm a male's chances. Therefore, the gene for a deep voice is expressed when inherited from the father and not when inherited from the mother.

- The ideal reproductive strategy is different for males and females. For example, maximum birth weight and fetal growth are favored by fathers because they increase offspring survival. Mothers favor maternal survival and the preservation of resources for future reproduction. Therefore, a mother may benefit from reduced fetal growth rates.

Epigenetics

- The inheritance of traits which are not encoded in the nucleotide sequence of DNA, but which are transmitted from mother cells to their daughter cells - Epigenetic effects are caused by changes in chromatin structure and in DNA methylation (epigenetic marks) - Epigenetic marks can also be transmitted from one generation of organisms to the next, though this is still somewhat controversial

Checkpoints integrate repair of chromosome damage with events of cell cycle ;

- The p53 Pathway - p53 - transcription factor that induces expression of DNA repair genes and CDK inhibitor p21 - p53 pathway activated by ionizing radiation or UV light (causing DNA damage) during G1 phase delays entry into S phase - DNA is repaired before cell cycle continues - If DNA is badly damaged, cells commit suicide (programmed cell death) - p53 plays a role in preventing tumor formation but is not necessary for normal cell function

What would be required to prove that a phenotype is caused by an epigenetic change? - The phenotype must be reversible in the presence of mutagenic compounds. - The phenotype must be the result of a nucleotide change that is present in one gender but not the other. - The phenotype must be unexplained by known genetic mechanisms. - The phenotype must be heritable with modified chromatin and an unaltered nucleotide sequence. - The phenotype must be passed to progeny only through the maternal DNA.

- The phenotype must be heritable with modified chromatin and an unaltered nucleotide sequence.

DNA damage checkpoints are crucial for preventing cell proliferation when DNA damage has occurred. The role of DNA checkpoint proteins in the cell cycle is closely tied to the roles of DNA repair enzymes, although these proteins perform different functions. Which of the statements is true for DNA checkpoint proteins and not true for DNA repair enzymes? - These proteins remove a single nucleotide of damaged DNA. - These proteins nick the phosphodiester backbone of the damaged DNA. - These proteins remove the region of damaged DNA. - These proteins pause the cell cycle if there is damaged DNA.

- These proteins pause the cell cycle if there is damaged DNA.

Select the mechanisms used by tumor suppressor proteins to prevent the initiation and progression of cancer. - They promote uncontrolled cell division. - They enhance cell growth by causing certain signaling pathways to remain constitutively active. - They repair base substitutions or breaks in DNA. - They induce apoptosis in response to DNA damage. - They act at cell cycle checkpoints to regulate progression through the cycle.

- They repair base substitutions or breaks in DNA. - They induce apoptosis in response to DNA damage. - They act at cell cycle checkpoints to regulate progression through the cycle.

Why are some stem cells referred to as totipotent? - Totipotent stem cells can divide indefinitely but can only differentiate into one type of cell in a multicellular organism. - Totipotent stem cells can differentiate into all cell types such that any daughter cell can become any type of cell in a multicellular organism. - Totipotent stem cells can differentiate into one of a limited number of different types of cells in a multicellular organism. - Totipotent stem cells cannot divide but can differentiate to become any type of cell in a multicellular organism.

- Totipotent stem cells can differentiate into all cell types such that any daughter cell can become any type of cell in a multicellular organism.

Monozygotic twins have identical DNA sequences, yet twins can differ in some physical or behavioral traits. What evidence suggests that epigenetic effects may cause these phenotypic differences in monozygotic twins? - Younger twins have more similar DNA methylation and histone acetylation patterns than older twins. - Older twins have more similar DNA methylation and histone acetylation patterns than younger twins. - Younger twins increase DNA methylation, whereas older twins increase histone acetylation. - Older twins increase DNA methylation, whereas younger twins increase histone acetylation.

- Younger twins have more similar DNA methylation and histone acetylation patterns than older twins.

Match each definition with the corresponding term concerning genes involved in tumor formation. Proto‑oncogenes Oncogenes Tumor suppressor genes Haploinsufficiency

- a gene regulating cell division that can be mutated into a tumorigenic form - a gene whose function drives uncontrolled cell division and tumorigenesis - a gene that protects a cell from progressing towards cancer - a condition in which a single copy of a gene fails to produce enough gene product for normal function

Which of the mutations described have the potential to cause cancer? - a loss‑of‑function mutation in a tumor suppressor gene - a gain‑of‑function mutation in a tumor suppressor gene - a loss‑of‑function mutation in a proto‑oncogene - a gain‑of‑function mutation in a proto‑oncogene

- a loss‑of‑function mutation in a tumor suppressor gene - a gain‑of‑function mutation in a proto‑oncogene

Changes that enable a tumor to disrupt local tissue and invade distant tissues

- ability to metastasize - angiogenesis - secrete substances that cause blood vessels to grow towards tumor - evasion of immune surveillance

Which description is the best definition of a stem cell? - a specialized cell that divides by meiosis to produce gametes in order to facilitate sexual reproduction - a type of lymphocyte made in the thymus that contributes an adaptive immune response - a type of blood cell that does not have a nucleus, mitochondria, or other organelles - an undifferentiated cell that can replicate itself indefinitely and differentiate into specialized cell types when appropriate

- an undifferentiated cell that can replicate itself indefinitely and differentiate into specialized cell types when appropriate

The role of environment mutagens in cancer

- concordance for the same type of cancer in first degree relatives (i.e. siblings) is low for most forms of cancer - cancer cannot be inherited - only predisposition to cancer can be - The incidence of some cancers varies between countries - when a population migrates to a new location, the cancer profile becomes like that of the indigenous population - numerous environmental agents are mutagens and increase the likelihood of cancer - some viruses, cigarette smoke, diet

DNA can undergo many types of modifications. One of these is methylation. Which bases are methylated more often in human DNA? - guanine - thymine - adenine - cytosine

- cytosine

In order to pass the G2/M checkpoint the cell must - have tension generated at the kinetochores. - be ready to pass into the G2 stage. - have all the enzymes needed for DNA replication available. - have sister chromatids already separated from each other. - have its DNA completely replicated and undamaged.

- have its DNA completely replicated and undamaged.

Which description applies to epigenetic gene regulation? - processing of exons in mRNA that results in a single gene coding for multiple proteins - heritable changes in gene expression that occur without altering the DNA sequence - a gene cluster controlled by a single promoter that transcribes to a single mRNA strand - mRNA modifications such as additions of a 5′5′ cap and 3′3′ poly‑A tail and removal of introns - protein modifications such as addition of a functional group, or structural changes such as folding

- heritable changes in gene expression that occur without altering the DNA sequence

Imprinting:

- mammals feature an unusual type of epigenetic silencing known as genomic imprinting -imprinting occurs in the germ line and affects at most a few hundred genes - it is accompanied by heavy methylation of DNA - imprinted genes are differentially methylated in the female and male germ lines - once imprinted, a silenced gene remains inactive during embryogenesis - imprints are erased early in germ-line development, then later reestablished

Which enzyme is responsible for the replication of chromosome ends in germ cells and certain proliferating somatic cells? - DNA ligase - geminin - DNA polymerase δ - topoisomerase - telomerase

- telomerase

DNA methylation silences gene expression in 2 different ways;

1. The presence of methylated CpG in the vicinity of the promoter interferes with transcription 2. The presence of methylated CpG attracts methyl-CpG-binding protein to the DNA which in turn recruits ATP-dependent remodeling complexes and histone deacetylases

The clonal nature of cancer

1. most cancers originate in a single cell - in this regard, a cancerous growth can be considered to be clonal 2. At the cellular and genetic levels, cancer is usually a multistep process cancers are clonal descendents of one cell

Key features of cancer cells:

Autocrine regulation Loss of contact inhibition Loss of apoptosis Loss of gap junction Telomerase activity Immortalized cells Metastasis Angiogenesis Evasion of immune surveillance

Methylation in somatic and germ-line cells during development in mammals...

DNA in both sperm and ovum is heavily methylated, but most methylation marks are removed during fertilization, except for paternally and maternally imprinted genes

Ferric-ketoglutarate-dependant Dioxygenase (AlkB) proteins are known to repair methylated basis without disrupting the sugar-phosphate backbone of the DNA strands

Direct DNA repair

Match each description to the appropriate stem cell type. Embryonic stem cell, Induced pluripotentstem cell (iPSC), or Both - Can be used to repair or replace damaged tissue - Can develop into any tissue type - Generated from a fertilized egg - Generated from an adult cell

Embryonic stem cell: - Generated from a fertilized egg Induced pluripotentstem cell (iPSC): - Generated from an adult cell Both: - Can be used to repair or replace damaged tissue - Can develop into any tissue type

Direct DNA repair

Enzymes that correct altered bases within the nucleotides e.g. photolyase, alkyltransferases, methyltransfere 6-O-methylguanine methyltransferase: removes the mutagenic methyl group

In utero stress or undernutrition may alter epigenetic marks (DNA methylation) in the genome of the fetus

Hypothesis: the epigenetic modifications prepare the fetus for a word that is stressful or where food is scarce - In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism

Match the checkpoint to its function. G1/S checkpoint G2/M checkpoint Spindle‑assembly checkpoint

Maintains cell until necessary enzymes for replication are synthesized Detection of DNA damage after replication Ensures that each chromosome is attached to spindle fibers from opposite poles

How does cancer differ from most other genetic disorders?

Most genetic disorders are inherited through germ cells from parents. Most cancers are, to some extent, the result of mutation in somatic cells that occur during an organisms lifetime.

Pre-implantation genetic diagnosis (PGD)

Ova are fertilized in vitro, embryos allowed to develop to the morula stage, and a single embryonic cell is removed from several. embryos are arrested in development DNA is PCR-amplified and genes are analyzed for the presence or absence of deleterious alleles Embryos that do not carry deleterious alleles are re-implanted to mother who will bring them to term This technology raises several ethical questions - "designer babies"

Proto‑oncogenes are genes that have the potential to become oncogenes through either mutation or an increase in expression. Classify the statements as describing proto‑oncogenes or tumor suppressor genes. - Mutations that increase activity of these genes may lead to cancer - These genes code for proteins that normally prevent uncontrolled cell division - Some products of these genes normally function in repairing damaged DNA - Mutations that decrease activity of these genes may lead to cancer - These genes code for proteins that normally promote cell division

Proto‑oncogenes: - These genes code for proteins that normally promote cell division - Mutations that increase activity of these genes may lead to cancer Tumor suppressor genes - These genes code for proteins that normally prevent uncontrolled cell division - Some products of these genes normally function in repairing damaged DNA - Mutations that decrease activity of these genes may lead to cancer

Which statement is true of cyclins? They function via an intracellular domain to which a signaling molecule can bind. They add methyl groups to histone proteins to assist in gene regulation. They normally speed up the cell cycle and cause abnormal cell proliferation. The levels of cyclin oscillate during the course of the cell cycle. They regulate the cell cycle by phosphorylating other proteins.

The levels of cyclin oscillate during the course of the cell cycle.

How might a mutation in a gene that regulates telomerase lead to cancer? The mutation could cause telomerase to be produced at abnormally low levels. The mutation could prevent telomerase from being expressed at all. The mutation could allow telomerase to be expressed when it should not be. The mutation could result in a nonfunctional telomerase protein. The mutation could cause telomerase to be expressed in germ cells and stem cells.

The mutation could allow telomerase to be expressed when it should not be.

Therapeutic cloning

The purpose of therapeutic cloning is to create stem cells that contain an identical genome. Tissues differentiated from genetically identical stem cells will not be rejected by the tissue recipient

The honeybee - Apis mellifera

The workers and the queen are both diploid females, with genomes that are indistinguishable at the DNA sequence level Worker - - Under-developed ovaries, lives a relatively short time, never mates or lays eggs, worker larvae, fed on "workers" food Queen - - Fully developed ovaries, lives about 20 times longer than workers, mates with males and lays about 200 eggs/day, as larva, fed "royal jelly"

Which statement is true of cyclin‑dependent kinases? They speed up the cell cycle and cause abnormal cell proliferation. They regulate the cell cycle by phosphorylating other proteins. They serve as receptors in signal‑transduction pathways. They bring about apoptosis within cancer cells. They add methyl groups to histone proteins to assist in gene regulation.

They regulate the cell cycle by phosphorylating other proteins.

In mammals, stem cells are commonly categorized based on

their developmental stage and their ability to differentiate

Totipotent cells

totipotent cells, like fertilized eggs can give rise to all cell types