03: Anatomy of the Gene

Question 1

Which base is this?

Answer 1

Adenine

Question 2

Which base is this?

Answer 2

Guanine

Question 3

Which base is this?

Answer 3

Thymine

Question 4

Which base is this?

Answer 4

Cytosine

Question 5

What is the sense strand?

Answer 5

The coding strand; the strand of DNA that has the same sequence as the mRNA.

Question 6

What is a gene and what are its components?

Answer 6

A sequence of chromosomal DNA that is required for the production of a functional product.

Has a promotor, enhancers, splice sites, exons and introns.

Question 7

What are microRNAs?

Answer 7

Untranslated genes which are ~22bp and control gene expression by translational repression or by loading the RNA Induced Silencing Complex (RISC), which destroys mRNA.

Question 8

What is a locus control region?

Answer 8

Segments of a gene which determine in part the chromatin structure and access to transcription factors.

Question 9

What components of a gene are important for transcription?

Answer 9

The TATA box and CAT box are immediately 5’ of the start of transcription.

The GC rich region often helps bind transcription factors.

Question 10

What are the splicing consensus sequences?

Answer 10

These consensus sequences include nearly invariant dinucleotides at each end of the intron, GT at the 5’ end of the intron, and AG at the 3’ end of the intron.

A is the branch site.

Question 11

How is DNA packaged?

Answer 11

• DNA is wrapped around histones to make chromatin.
• Each histone octamer has DNA wound around it twice (a nucleosome) for a total of 140bp.
• Long strings of nucleosomes are further compacted into solenoids, which attch to the scaffold/matrix within the nucleus to form loops.
• Less tightly packaged areas are better able to bind transcription factors (euchromatin).

Note: There is also a mitochondrial genome which is 16kb in length and maternally inherited.

Question 12

What is ChIP-sequencing?

Answer 12

Analysis of protein interactions with DNA. Combines chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing to identify binding sites of DNA-associated proteins.

Question 13

What is DNase-Sequencing?

Answer 13

Analysis of the location of regulatory region, based on genome-wide sequencing of regions super sensitive to cleavage by DNase I.

Question 14

Whatis the significance of 5p13.1?

Answer 14

Gene desert, but contains SNPs associated with inflammatory diseases (Crohn’s disease, Ulcerative colitis, Multiple sclerosis).

Genetic variants modulate the expression of flanking genes; affect occupancy of a GATA factor in an allele-specific manner.

Question 15

What is the signal sequence for the Poly A tail?

Answer 15

AAUAAA

Question 16

What is uniqe about the first exon of a gene?

Answer 16

Very CG rich to allow for binding of transcription factors.

Question 17

What DNA sequence establishes the reading frame?

Answer 17

ATG; template for AUG (methionine).

Question 18

Describe the globin gene family.

Answer 18

Grew as a result of multiple gene duplications; now located on chromosomes 11 & 16 (alpha).

Multiple alpha/betagene family members expressed differentially during development to allow for transportof oxygen under various oxygen tensions.

Many globin genes are pseudogenes: nonfunctional, vestigial remnants of previously functional genes.

Question 19

What are transposable elements?

Answer 19

DNA segments which can change their position within the genome (may even be inserted in middle of previously functional gene).

This is the cause of hemophilia (factor VIII).

Question 20

What is the genetic basis of Hemophilia B Leyden and Hemophilia B Brandenburg?

Answer 20

Both result from promoter mutations which decrease the production of Factor IX.

Leyden improves at pubery when levels of androgen increase.

Brandenburg Factor IX levels remain low even after puberty.

Question 21

What is Huntington’s Disease?

Answer 21

A triple repeat disease (CAG) in which pathological changes in repeat sequences disturb the function of a gene.

(CAG)_10-26 normal

(CAG)_27-35 at risk for expansion

(CAG)_35-41 variable penetrance

(CAG)_42-121 affected

Trinucleotide repeats (TNRs), if in coding region, cause long runs of amino acids that affect protein function. If in non-coding regions, can affect gene expression.

Question 22

Large deletions are commonly seen in what two conditions?

Answer 22

Alpha thalassemia

Duchenne muscular dystrophy