Human Genetics Final

What is the purpose of "Caretaker" genes?

"Caretaker" genes, like DNA repair genes, help maintain the integrity of the genome. They control mutation rates and may have an overall effect, when mutant destabilizing the genome

What are 5 examples of Proto-oncogenes?

-growth factors -receptors -kinases -GTPase -transcription factors

Oncogene (mutant form) can lead to cell division and cancer in several different ways. Name them.

1) mutation in exon so protein is always in activated form, 2) amplification so overexpresed, 3) mutation in promoter OR gene moved to new promoter so expressed at the wrong time, wrong place or over expressed 4) virus inserted upstream so gene is over expressed from viral promoter

List four characteristics of cancer cells

Cancer cells: a) divide continually (oncogenes, loss of contact inhibition, loss of tumor suppressors); b) divide indefinitely (activated telomerase); c) have sustained angiogenesis; d) dedifferentiate e) invade and spread (metastasis) f) have increased mutation rate (contain heritable mutations);

Are proteins like retinoblastoma (eye cancer) and BRCA 1or 2 found in other cells? Are they important in other forms of cancer?

Commonalities will become apparent as we learn more, i.e. as many as 50% of all cancers are missing the p53 protein.

What type of mutations in tumor suppressor genes and proto-oncogenes lead to cancer (loss of function/gain of function)? Are they inherited in a dominant or recessive manner? Why is retinoblasma referred to as dominant? Describe (on the molecular level) three types of mutations that lead to oncogenes.

Loss of function mutations in tumor suppressor genes can lead to cancer. They are inherited in a recessive manner (but are classified as autosomal dominant when chance of second mutation is high). Gain of function mutations in proto-oncogenes can lead to cancer. They are inherited in a dominant manner.

What are the two types of early mutations that can lead to cancer?

Mutations in Caretaker genes (control DNA repair and chromosome integrity) lead to increase in mutation rate Mutations in Gatekeeper genes (tumor suppressor and proto-oncogenes) can lead to increased cell division and an increase in target size for later mutations

Are all cancers caused by the same mutations?

No, as illustrated above different cancers are caused by different mutations in different genes.

Why do some cancers only require one-hit?

Some cancers (Hereditary retinoblastoma) may require only one hit because: 1) susceptible cells are still relatively undifferentiated, 2) one mutant copy was inherited, and 3) just one mutational hit can result in loss of heterozygousity (LOH) or absence of a functional Rb gene.

Define tumor suppressor genes and proto-oncogenes.

Tumor suppressors are genes encoding proteins that suppress cell division. Proto-oncogenes are genes encoding proteins that promote cell division.

Compare and contrast the two-step (two-hit) and the multiple-hit theory of cancer?

Two step model (TWO HIT)- cancer in 2 mutations same gene Multiple hit model- Most cancers are caused by mutations in two or more gene that accumulate over time

Which of the following mutations could lead to cancer? (circle all that apply) a. homozygous recessive mutations in a tumor suppressor gene coding for a nonfunctional protein. b. dominant mutations in a tumor suppressor gene in which the normal protein product is overexpressed c. homozygous recessive mutation in which there is a deletion in the coding region of a proto-oncogene, leaving it nonfunctional d. dominant mutation in a proto-oncogene in which the normal protein product is overexpressed e. all of the above

a. homozygous recessive mutations in a tumor suppressor gene coding for a nonfunctional protein. d. dominant mutation in a proto-oncogene in which the normal protein product is overexpressed

What are Proto-oncogenes?

are normal genes that initiate or maintain cell division in a highly controlled manner

Familial retinoblastoma appears to be inherited as a dominant trait. What factors(s) account for this? (see chapter question 5a) a. a dominant mutation is transmitted through the germ line. b. somatic mutation occurs after a recessive mutation is transmitted through the germ line. c. heterozygous individuals are infected with a retrovirus d. about half of the homozygous, normal individuals in an affected family are infected with a retrovirus at birth e. It a loss of function mutation so it has to be recessive

b. somatic mutation occurs after a recessive mutation is transmitted through the germ line.

A proto-oncogene is a gene that: a. normally causes cancer b. normally suppresses tumor formation c. normally functions to promote cell division d. is involved in forming only benign tumors e. is only expressed in blood cells f. all of these are true

c. normally functions to promote cell division

What are Oncogenes?

cancer causing genes; mutations that result in uncontrolled cell growth (Gain of Function). One copy can promote cell division

Cancer cells bypass _____ _______ ______ ______

cell cycle check points.

Early mutations in DNA repair genes and chromosomal integrity genes do what?

increase the mutation rate.

Early mutations that increase cell division do what?

increase the target size for later mutations.

Loss of function of retinoblastoma results in what?

malignant tumor of the embryonic retinal cells

What do Gatekeeper Genes directly control?

mitosis and apoptosis

Which Gatekeeper gene stimulates cell division?

protooncogenes

What are the two types of "Gatekeeper" genes?

protooncogenes and tumor suppressors

What is the purpose of "Gatekeeper" genes?

regulate the cell cycle and therefore cancer

Retinoblastoma is a _______

tumor suppressor gene

Which Gatekeeper gene suppresses cell division?

tumor suppressors