Genetics Week 3

Question 1

The TENDENCY for genes or segments of DNA closely positioned along a chromosome to segregate together at meiosis and therefore be inherited together is called………

Answer 1

Linkage

Do not confuse with linkage disequilibrium.

Question 2

How do you analyze linkage?

Answer 2

Indirect DNA analysis: The use of several DNA markers (normal variants) that are NEAR or WITHIN a gene of interest to track within a family the inheritance of a disease-causing mutation in that gene.

Question 3

What’s the other word for haplotype she likes to use?

Answer 3

Phase

Question 4

Define Linkage Disequilibrium.

Answer 4

THe co-occurrence of specific alleles at a higher frequency than would be predicted by random chance.

AKA: the overrepresentation of specific haplotypes within a population

Question 5

If recombination frequency determines the extent of linkage, what relationship do 2 genes on the same chromosome that never recombine have?

Ones that have a tendency to recombine together?

Ones that almost ALWAYS recombine together?

Answer 5

Unlinked loci.

Linked Loci

Linkage disequilibrium

Question 6

What is the difference between direct and indirect genetic testing methods?

Answer 6

In direct testing, you’re looking for a KNOWN DISEASE ALLELE, and can specially target the gene of interest.

In INDIRECT testing, you’re looking for an UNKNOWN DISEASE ALLELE, using multiple, CLOSELY LINKED, flanking markers.

Use linkage to your advantage.

Question 7

What type of DNA is used for linkage analysis? (AKA indirect testing)

Answer 7

Usually flanking SNPs. But you can use any known variant of DNA that is in linkage with an unknown causative mutation.

Question 8

Can you use intragenic markers for indirect testing, or must you use extragenic markers?

Answer 8

INTRAGENIC are actually the best to use, as long as they flank the mutation of interest. The risk of unintentional recombination is lowest here, so most accurate test results are obtained.

Question 9

WHy must the genetic marker you’re tracking with indirect testing be Heterozygous?

Answer 9

Homozygous markers are not informative in most situations. A heterozygous marker yields phenotypic differences?

I’m a bit confused on this point.

Question 10

What’s the biggest risk of indirect linkage analysis?

Answer 10

We aren’t even looking in the right place…

Question 11

A kid has bilateral retinoblastoma. Is it hereditary or nonhereditary?

Answer 11

Hereditary. Individuals that inherit a hemline mutation in one allele only need one more hit (mutation) in the remaining normal allele of any retinoblast for cancer to occur.

Question 12

How many mutations must have accumulated in a person with unilateral retinoblastoma?

Answer 12

In most cases of non-hereditary retinoblastoma, there is NO original mutation inherited from the parental germ line, so 2 hits (mutations) must occur before cancer formation.

Question 13

what’s the mutated gene in retinoblastoma called?

Answer 13

RB1

Question 14

What does the phrase “Loss of Heterozygosity” mean?

Answer 14

A heterozygous cell receives a second hit in its remaining functional copy of the tumor suppressor gene, becoming homozygous for the mutated gene.

Question 15

Mutations that affect tumor suppressor genes are LOF or GOF?

Answer 15

LOF

Generally point mutations, chromosomal deletions, or somatic recombination gone wrong.

Question 16

What is the function of a tumor suppressor gene?

Answer 16

Inhibit cell division and cell proliferation

Stimulate death

Repair damaged DNA

Question 17

T/F: You can inherit cancer.

Answer 17

FALSE! You can inherit a mutation that gives you a tendency towards the development of cancer (high risk), but cancer ALWAYS involved ACQUIRED MUTATIONS.

Question 18

What are the 2 broad classes of cancer genes and a few facts about each?

Answer 18

1. Oncogenes
   - Growth promoting
   - Gas pedal
   - GOF
2. Tumor Suppressor Genes
   - Grwoth Restricting
   - Brake pedal
   - LOF