Human Genetics

Question 1

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Identify the two major classes of normal genes that can mutate and lead to cancer. Describe their normal functions.

Answer 1

The two major classes of normal genes that can lead to cancer after undergoing mutations are 1) the tumour suppressor genes that normally repress cell division, and 2) the proto-oncogenes, the normal function of which is to promote cell division.

Question 2

Name three mechanisms by which proto-oncogenes can be converted into oncogenes.

Answer 2

Three mechanisms by which proto-oncogenes can be converted into oncogenes are point mutations, translocations, and over-expression. The latter includes amplification and the acquisition of a new promoter or enhancer.

Question 3

What is the Philadelphia chromosome?

Answer 3

forms when chromosome 9 and chromosome 22 break and exchange parts. This creates a short chromosome 22 and a new combination of instructions for the cells. These new instructions can lead to the development of chronic myelogenous leukemia.

Question 4

What are the two fundamental properties shared by cancer cells?

Answer 4

1. proliferation: abnormal gell growth and division
2. metastasis: defects in the normal restraints that keep cells from spreading and colonizing other parts of the body

Question 5

What is a benign tumor?

Answer 5

a multicellular mass caused by a cell losing its genetic control over cell growth
* can be removed by surgery and cause no serious harm

Question 6

What is a malignant tumor?

Answer 6

when cells in the tumor have the ability to break loose, enter the bloodstream, invade other tumors and form secondary tumors (metases)
* difficult to treat and often life-threatening

Question 7

Do cancers arise from single mutations or multiple mutations?

Answer 7

cancers arise from the accumulation of many mutations in many genes
* mutations that lead to cancer affect multiple cellular functions, including repair of DNA damage, cell division, apoptosis, cellular differentiation, migratory behavior, and cell-cell contact

Question 8

what does “the clonal origin of cancer cells” mean?

Answer 8

all cancer cells in primary and secondary tumors are clonal, meaning that they originated from a common ancestral cell that accumulated specific cancer-causing mutations

Question 9

What kinds of cancers are characteristically related to reciprocal chromosomal translocations?

Answer 9

• leukemias
• lymphomas
• (hint: both involve white blood cells)

Question 10

What are driver and passenger mutations?

Answer 10

• driver mutations: mutations that give growth advantage to a tumor cell (onlt a handful in each tumor, between 2-8)
• passenger mutations: the remainder of mutations acqured over time that have no direct contribution to the cancer phenotype

Question 11

What is the cancer stem cell hypothesis?

Answer 11

most of the cells within tumors do not proliferate
* those that do not proliferate are known as cancer stem cells
* contrasts models that predict that every cell within a tumor has the potential to form a new tumor

Question 12

What is the rate of mutations in humans?

Answer 12

10^-6 mutations per gene, per cell division, mainly due to the intrinsic eror rates of DNA replication

Question 13

What is the rate of cancer in humans?

Answer 13

1/3

Question 14

What are carcinogens and how do they contribute to the hypothesis of cancer being a multistep process?

Answer 14

cancer-causing agents
* exposure to carcinogens and appearance of cancer is delayed by an incubation period

Question 15

What is tumorigenesis?

Answer 15

the development of a malignant tumor

Question 16

What are the steps of developing colorectal cancers?

Answer 16

1. conversion of normal epithelial cell into small cluster of cells called a polyp (or adenoma). this requires inactivating mutations in APC gene.
2. acquisition of second genetic alteration in one of the cells within the small polyp. usually mutation in KRAS gene.
3. transforms the a large polyp into a malignant tumor (carcinoma) is caused by defects in several genes

Question 17

What is the mutator phenotype?

Answer 17

the high level of genomic instability seen in cancer cells - less ability to repair DNA damage and increases susceptibility to cancer-causing driver mutations

Question 18

What is epigenetics?

Answer 18

the study of chromosome-associated changes that affect gene expression but do not alter the nucleotide sequence of DNA

Question 19

At what stage of the cell cycle do cancer cells bypass?

Answer 19

cancer cells cannot enter the G0 (stop) phase of the cell cycle where cells do not divide but remain metabolically active.
* cancer cells are unable to enter G0
* they continuously cycle
* the rate of proliferation is not greater than a normal cell, they just do not stop at the proper time or place

Question 20

what is signal transduction and how does it relate to cancer cells?

Answer 20

signal transduction is the process of transmitting growth signals from the external environment to the cell nucleus (tell the cell to reenter the cell cycle because there is a need for it e.g. healing)
* in cancer cells, there are often defects in the signal transduction pathways
* sometimes abnormal signal transfuction molecules send continuous growth signals to the nucleus (when not needed)

Question 21

Should you perform presymptomatic testing for Huntington’s disease on your children to determine if they have inherited the disorder?

Answer 21

It is very clear that minors should never be tested presymptomatically, and that the decision to be tested must be the sole choice of the person concerned. Requests from third parties, be they family members or otherwise should never be considered.

Question 22

You are a genetic counsellor and Winnie (27) comes to your clinic regarding her late father’s Huntington diagnosis, wanting to know if she has inherited it. She also wants to marry a man named Peter and wants to know if he will be a carrier. What information will you provide her with?

Answer 22

1. verify that the father’s diagnosis is right and not just an assumption.
2. make sure that information regarding the disease, its course and development, its inheritance and risk of occurrence in the present and next generations is well understood.
3. discuss the availability, possibility, and implications of testing, and to encourage Winnifred to choose a companion (friend, relative, or Peter, depending on the relationship) to accompany her throughout the various stages before, during, and after the test if she decides to go through with it.
4. address, if necessary, the distinction between marriage and parenthood and discuss, if appropriate, other forms of parenting like adoption or ovum transfer.
5. provide, if not already known, further information about research and DNA banking options for affected and older unaffected individuals, their spouses, and seriously affected family members who have not been tested.

Question 23

Give some real-world examples of genetic screening and testing.

Answer 23

1. PKU screening in newborn babies
2. Sickle-cell anemia carrier testing (autosomal recessive disease) in Africa
3. Cytogenetic examination of amniotic fluid (amniocentesis) of older women to test for Down Syndrome
4. Maternal Serum Screening Program (neural tube defects, trisomy 18, trisomy 21)

Question 24

Mrs. van der Westhuyzen is only 22 years old and knows women over 35 have an increased probability of having children with Down syndrome. She therefore decides not to have a maternal serum screen done. Is she right?

Answer 24

A decision to undergo maternal serum screening should not be based on age alone. The question Mrs. van der Westhuyzen should ask herself is whether she wants to know if she has a higher probability of having a child with Down syndrome or a neural tube defect. If she does not want to know, she should not undergo screening. If she wants to know, the best way to find out is to undergo serum screening with due consideration given to biochemical findings, her own age, her gestational age, her weight, diabetic status, etc. Any decision based on only one, rather than all these criteria, does not seem to be wise.

Question 25

Cathy wants to undergo maternal serum screening. She is also strongly opposed to abortion. A friend argues that she is inconsistent. Is her friend right?

Answer 25

Cathy’s friend is wrong. The goal of maternal screening is not to abort but to offer options (one of which may be the termination of pregnancy). Advanced knowledge and awareness of a higher risk or of a confirmed abnormality after testing are also desirable options that will help future parents get prepared and cope better with abnormality during or after pregnancy.
(In fact, most maternal serum screens with abnormal results are followed by tests with normal results and normal births, while the occasional non-births are more often due to miscarriages than to therapeutic terminations of pregnancies.)

Question 26

What are tumor-suppresor genes? What is their role in normal cells and what happens in cancer cells?

Answer 26

genes whose products normally regulate cell-cycle checkpoints or initiate the process of apoptosis
* in noral cells, TSG halt progress of proteins through the cell cycle in response to DNA damage or growth-suppresion signals
* when TSG are mutated or inactivated, cells are unable to respond normally at cell-cycle checkpoints
* this leads to the accumulations of more mutations and cancer

Question 27

What are proto-oncogenes? What are their role in normal cells and what happens in cancer cells?

Answer 27

genes that cause normal cells to become cancerous when mutated
* they ecnode transcription factors that stimulate expression of other genes, signal transduction moecules that stimulate cell division, and cell-cycle regulators that move the cell through the cell cycle
* in normal cells, when they go quiescent and cease division, they repress the expression of proto-oncogenes or modify the activities of their products
* in cancer cells, protooncogenes are altered so that activities of their products cannot be regulated

Question 28

Give examples of proto-oncogenes.

Answer 28

c-myc: transcription factor, regulates cell cycle, differentiation, apoptosis
- in cancer: translocation, amplification, and point mutations; lymphomas, leukemias, lung cancer, etc.

c-kit: tyrosine kinase, signal transduction
- in cancer: mutation; sarcomas

Question 29

Give some examples of tumor-suppresor genes.

Answer 29

RB1: cell-cycle checkpoints, binds E2F
- in cancer: mutation, deletion, inactivation by viral oncogene products; lung, esophagus cancers and more

TP53: transcription regulation
- in cancer: mutation, deletion, viruses; many types of cancers

BRCA1, BRCA2: DNA repair
- in cancer: point mutations; breast, ovarian, and prostate cancers

Question 30

Where do inherited cancer-susceptibility alleles occur?

Answer 30

tumor-suppresor genes
- they are not usually sufficient to trigger development of cancer
- at least one other somatic mutation is necessary to express the cancer phenotype

Question 31

What are some of the most mutagenic agents (carcinogens)

Answer 31

• natural substances and processes
• aflatoxin (mold), nitrosamines (naturally occurring), natural pesiticides and antibiotics found in plants

Question 32

What are the natural environmental agents that can cause cancer?

Answer 32

• natural carcinogens (molds, nitrosamines, pesticides, and antibiotics)
• radiation
• UV light and ionizing radiation
• diet

Question 33

What are some human-made chemicals and pollutants?

Answer 33

• air pollution
• tobacco smoke

Question 34

What is the FISH technique and what is it used for?

Answer 34

FISH: fluorescence in situ hybridization
* used to identify chromosmoal locations housing specific genetic information
* the full set of chromosomes from an individual is affixed to a glass slide and then exposed to a “probe”—a small piece of purified DNA tagged with a fluorescent dye. The fluorescently labeled probe finds and then binds to its matching sequence within the set of chromosomes. With the use of a special microscope, the chromosome and sub-chromosomal location where the fluorescent probe bound can be seen.