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Outline
The Genetic Dogma
Part 1: DNA and Chromosome Structure
Part 2: The Language of the heredity: from
DNA to Protein
Part 3: Regulation of Gene Expression
Mutations
Part 4: Where things goes wrong?
tRNAs
SINEs
siRNAs
parents
DNA
RNA
Reverse transcription
children
protein
function
parents
DNA
Mendelian
RNA
Autosomal dominant
- Autosomal recessive
- X-linked
- Y-linked
protein
function
Mitochondrial - eg diabetes-deafness
children
Mosaic
- eg McCune-Albright
Imprinting
- eg
Prader-Willi Syndrome
Uniparental disomy
Multigenic
DNA Structure
5 end
Long chain of polymer
(polynucleotide)
The basic shape is like a
twisted ladder or zipper
(double helix).
3 end
3 end
Types of RNA
1. mRNA (messenger): takes a message from the nucleus to
the ribosomes in the cytoplasm
2. tRNA (transfer): transfers amino acids to the ribosomes
3. rRNA (ribosomal): along with proteins, makes up the
ribosomes where polypeptides are synthesized.
4. smRNA, snoRNA and microRNA
DNA Organization
Helix
Nucleosomes
Solenoid
Chromomere
Chromatin
Chromosome
P arm
Nucleolus
Euchromatin
centromer
Hetrochromatin
q arm
Nucleus
1. Lies on chromosome
2. Able to store information
3. Stable so that it can be copied and passed on
through generation
4. Able to undergo rare changes called mutations
in order for evolution to occur
Summary: part 1
DNA consists of two complementary chains
of nucleotides
The double-helix is the mechanism for
heredity
DNA resides in the nucleus (eukaryotes)
DNA is packaged in chromosomes
Chromosomes contain long strings of
genes
DNA
Genotype
Transcript
RNA
Translation
Protein
phenotype
III
III
holes)
Gene Structure
ATG (Initiation site)
Regulatory region
Transcription
Recognition of the promoter
START
Regulatory elements
core promoter
TATA box
Transcription
{
IIE
IIB
Transcription factors
IID
Pol II
IIH
Promoter
II
Transcription
{
Pol II
..CAUG..
..GTAC..
1. Initiation
2. Elongation
3. Termination
RNA product
RNA Processing
7-Methyl G (Guanosine)
Poly A Tail
(AAAAAA)n
AUG
UAA
Mature RNA
5 UTR
UTR 3
Transcription
{
CAP
AAAAAAAAAAAAAAn
Pol II
Transcription
Splicing exons (introns removed)
Introns
AAAAAAAAAAAAAAn
CAP
Exons
Transcription
Messenger RNA is exported from
the nucleus to cytoplasm
CAP
AAAAAAAAAAAAAAn
RNA Transportation
Summary of Transcription
Recognition of the promoter
RNA polymerase transcribes RNA from DNA
RNA transcript undergoes modification
Splicing exons (introns removed)
Messenger RNA is exported from the nucleus
to cytoplasm
genetic 'word'
Translation
The ribosome:
Transfer RNA
Amino acid
Anti-codon
Translation Steps
1. ACTIVATION
add an amino acid to tRNA
Translation Steps
2. INITIATION
Assemble players [ribosome,
mRNA, aa-tRNA]
Translation Steps
3. ELONGATION
Translation Steps
4.TERMINATION
Translation
methionine
Leu
Ile
Met
UAC
AUG
mRNA
Phe
Leu
Val
C
Ser
Tyr
Cys
stop
stop
Trp
stop
U
C
A
G
Pro
His
Gln
Arg
U
C
A
G
Thr
Asn
Lys
Ser
Arg
U
C
A
G
Ala
Asp
Glu
Gly
U
C
A
G
Translation
UAC
AUG
Translation
Translation
U
U
Phe
Leu
Leu
Ile
Met
Val
C
Ser
Tyr
Cys
stop
stop
stop
Trp
stop
U
Post-translational
modification
C
A
G
Pro
His
Gln
Arg
U
C
A
G
Thr
Asn
Lys
Ser
Arg
U
C
A
G
Ala
Asp
Glu
Gly
U
C
A
G
UAG
Summary of Translation
mRNA sequence is decoded in sets of three
nucleotides called codons
Each codon specifies an amino acid
Each mRNA therefore encodes a polypeptide chain
Although there are 3 possible reading frames
for mRNA, only one is used
Post-Translation Process
Hsp60
Hsp70
Post-translational modifications
z
Glycosylation
phosphorylation
Disulfide bonds
Summary: part 2
A gene is DNA that is transcribed into RNA
RNA is complementary to one DNA strand
RNA is modified before export from the
nucleus
mRNA sequence is decoded in triplet
nucleotides by ribosomes
tRNAs are the bridge between RNA codons
and cognate amino acids
Proteins are folded and processed to
achieve function
DNA
RNA
protein
function
Which protein
How much
When (timing)
In what combination
Gene Regulation
Why genes are regulated?
It would be a waste of cellular energy and
materials if every gene was constantly being
actively transcribed.
Some genes are rarely used, and only in specific
cells.
Different genes need to be activated at different
times, depending on location in the body and
time.
Ac
Ac
Histone
complex
Histones acetylated
=transcription facilitated
Histones deacetylated
=transcription repressed
Histone
Deacetylase
switch
Histone
Acetylases
2. Post-Transcriptional Regulation
3. Transltional Regulation
- Availability of tRNA, amino acids, etc.
- Shelf Life of mRNA
- Hormones-affect stability
4. Post-Transltional Regulation
- Activated proteins- enzyme cleavage
* Removal of "signal" peptide sequences
* Addition of sugar residues (glycosylation)
* Phosphorylation etc
- Degradation of proteins
GENETIC CHANGE
Change in DNA nucleotide sequence
Mutation
Methylation
Methylation of cytosines=silencing
Eg X chromosome inactivation
Important cause of imprinting
Too much or too little methylation can
cause imprinted disorders
Beckwidth-Wideman syndrome
Angelman syndrome
DNA Mutations
Promoter mutations
Reduce gene expression
Eg some cases of alpha and beta thalassemia
are due to mutations in promoter or enhancer
sequences for the alpha or beta globin genes.
Different gene expressed
Eg glucocorticoid-remediable hypertension is
due to fusion of the promoter region of the
gene for CYP11B1 and the coding sequences of
CYP11B2, resulting in ACTH-dependent
activation of the aldosterone synthase
Mutations (Where?)
Somatic mutations
- happens in a non-germ line cell
- organism becomes a mosaic
- are the cause of some cancers
Germ-line mutations
- occurs in the cells that give rise to gametes
- gamete will carry the mutation to the next generation
- germ-line mutations are heritable
Mutation
silent
Any questions?