Gene Structure

Question 1

Example of closely related gene cluster and how they are formed

Answer 1

B-globin

Duplication and then divergence

Question 2

Each gene of B-globin cluster has

Answer 2

Own promoter

Question 3

SNP

Answer 3

Single nucleotide polymorphisms

Most of genetic variation

Question 4

INDELS

Answer 4

INsertions and DELetions

Question 5

Microsatellites

Answer 5

SSR repeats of 2-5 BP

Also called variable tandem number repeats

Question 6

Interspersed repeat sequences

Answer 6

SINES (Short interspersed repeated elements)

LINES (long interspersed repeated elements)

Question 7

CNV

Answer 7

Copy number vairations
Direct repeats at a locus
***Account for differences in amount of gene produced

Question 8

Microsatellite disease

Answer 8

HNPCC (hereditary non-polypsis colorectal cancer)

Question 9

HNPCC caused by

Answer 9

Changes in microsatellite repeat length (MSI)

Microsatellite instability

Question 10

PCR will show what in MSI?

Answer 10

Extra products in tumor tissue vs normal

Question 11

Colon cancer signs

Answer 11

Constipiate 
Diarrhea
Blood in stools 
Narrow stools 
unexplained anemia 
Abdominal pain 
Unexplained weight loss
Weakness and fatigue

Question 12

Sporadic cancer

Answer 12

Blood - inherited CNVs

Tumor - Inherited and tumor specific CNVs

Question 13

Inherited cancer

Answer 13

Blood - inherited CNVs
Blood - Inherited and acquired CNVs
Tumor - inherited, acquired, and tumor specific CNVs

Question 14

c-MYC is example of

Answer 14

proto-oncogene

Question 15

In Burkitt’s lymphoma, c-MYC moves next to _____

Answer 15

H chain enhancer on chromosome 14 near IGH

Question 16

snRNPs

Answer 16

small nuclear ribonucleoproteins that perform splicing reactions

Question 17

Consensus sequences in precursor mRNA for splicing

Answer 17

5’ splice (GU)
3’ splice (AG)
Site just 5’ to the 3’ site called the branch site

Question 18

Steps of splicing

Answer 18

1) snRNPs associate with splice site sequences to form splicesome
2) 2’ OH of branch site A nucleotide attack phosphodiester bond at junction of 5’ splice site…cleaves to form 3’ OH at 5’ end
3) 3’ OH at 5’ splice site attack and covalently bonds to 3’ splice site…this is joining of splice site and intron released

Question 19

Alternative splicing means

Answer 19

Can get multiple functional proteins from 1 mRNA

Question 20

FGFR-2 splicing

Answer 20

Can result in different affiinities for different ligands based on alternative splicing

Question 21

Alternative splicing of Bcl-x

Answer 21

BCLx- short - pro-apoptotic

BCLx-long - anti-apoptotic

Question 22

Tissue dependent alternative splicing

Answer 22

mRNA making calcitonin and CGRP are from same
In thyroid - makes calcitonin
In brain - makes CGRP

Question 23

Cryptic splice site

Answer 23

Sequence with some similariyt to a splice site and can be used at a low rate by splicing machinery or a high rate if mutated

Question 24

Altered globin mRNA splicing can lead to

Answer 24

Thalassemias - less functional hemoglobin

Question 25

Intron 1 cause of B thalaseemia

Answer 25

Site within intron 1 becomes better 3’ acceptor than normal. 90% of mRNA made is wrong…RNA will be decayed

Only 10% is normal

Question 26

Spinal Muscular Atrophy

Answer 26

Mutation in SMN2 gene that causes exon 7 to be skipped…leads to unstable SMN2 protein
Still have SMN1 protein but not enough

Question 27

Therapeutics for thalassemias and other aberrant splicing diseases

Answer 27

Antisense oligonucleotides

Base-pair to mRNA sequences in mRNA representing new cryptic sites…this supresses their use