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Genes

A gene is a unit of
inheritance occupying
a specific site (locus)
on a chromosome,
which is associated
with regulatory
regions, transcribed
regions and/or other
functional sequence
.regions

Chromosomes

Chromosomes

.Chromosomes serves as a molecular package for carrying DNA in cells


They can be considered as vehicles by which hereditary information is
.physically transmitted from one generation to the other

Central Dogma of Molecular


Biology

Genes coding proteins

Exon/intron boundaries in genes; mRNA


splicing

Transcription copies the DNA code of a gene and converts it to messenger RNA (m RNA). The m
RNA will be used at the ribosome to make polypeptides (proteins). However all of the code
contained in the m RNA molecule is not needed to produce the polypeptide. The sections of m
RNA which do not code for translation of polypeptide are called introns. As the m RNA readies
itself to leave the nucleus, enzymes cut out and remove the introns. The remaining exons are
spliced back together again by a different enzyme. This modified m RNA is what comes to the
.ribosome to be translated into polypeptides

mRNA copy stabilized with 5 cap


and poly-A tail

The mature mRNA transcript can now leave the nucleus for the cytoplasm

Transcription and Translation

mRNA copy

Kinds of RNA required for protein


synthesis
Messenger RNA (mRNA)
Messenger RNA contains genetic information. It is a copy of a
.portion of the DNA
It carries genetic information from the gene (DNA) out of the
nucleus, into the cytoplasm of the cell where it is translated to
.produce protein
Ribosomal RNA (rRNA)
This type of RNA is a structural component of the ribosomes. It
.does not contain a genetic message
Transfer RNA (tRNA)
Transfer RNA functions to transport amino acids to the ribosomes
.during protein synthesis

The Genetic Code


Triplet Codons and Corresponding Amino Acids
U

UUU
UUC
U

UUA

C
Phe

Leu

UCU

UAU

UCC

UAC

UCA

Ser

UAA

UUG

UCG

UAG

CUU

CCU

CAU

CUC
CUA

Leu

CCC
CCA

Pro

CAC
CAA

CUG

CCG

CAG

AUU

ACU

AAU

ACC

AAC

AUC

Ile

AUA
AUG

ACA
Met

GUU
G

GUC
GUA
GUG

Val

Thr

AAA

ACG

AAG

GCU

GAU

GCC
GCA
GCG

Ala

GAC
GAA
GAG

G
Tyr

STOP

His
Gln
Asn
Lys
Asp
Glu

UGU
UGC

Cys

UGA

STOP

UGG

Trp

CGU
CGC
CGA

Arg

CGG
AGU
AGC
AGA
AGG

Ser
Arg

GGU
GGC
GGA
GGG

Gly

tRNA and a ribosomal


complex

.Initiation: The beginning of the translation process. 1


To begin translation, the large (top) and small (bottom) ribosomal units must be bound together to
the strand of mRNA. This process is called initiation. Initiation begins as rRNA polymerase on the
ribosome binds the ribosomal units to the mRNA. The ribosomes position themselves so that the
codon sequence AUG (the "start" codon) on the mRNA is exposed. A tRNA unit with the anticodon
sequence UAC bonds to the exposed "start" codon. This first tRNA only carries the amino acid
. methionine (met) which is now set in place
Initiation thus largely consists of placing this first tRNA and its associated amino acid (met) in
.place on the mRNA

Reference: Long and Slichter

Elongation: It is the process where special elongation proteins assist a new tRNA and its . 2
associated amino acid to bond to the complementary codon on mRNA. Ultimately, this helps
.lengthen (elongate) the polypeptide chain
As the large ribosomal unit sets in place, the second codon on mRNA is exposed (in this case,
the codon is CAU). This exposed site is known as the A site. At this point, a special protein unit
known as the elongation factor assists the 2nd tRNA to bond to this newly exposed codon. The
GUA of the antidodon (t RNA) bonds to the codon of CAU. At this point, the newly arrived amino
acid (his) is lined up next to the 1st amino acid (met). An enzyme binds both amino acids via
. dehydration synthesis (loss of water) bonding

When the 1st two amino acids have bonded, the first tRNA leaves the mRNA/ ribosomal complex

Translocation: In this step, the ribosomal unit physically moves (translocates) . 3


3 bases (a new codon: AUG) along the mRNA in the 5' ---> 3' direction. When the
new codon is exposed, another elongation protein assists the new tRNA and its
associated amino acid (Ser) to bind to the codon. After this occurs, an enzyme
.binds the amino acids His and Ser via dehydration synthesis

4. Termination: The end of the translation process.


The diagram above illustrates the ribosomal complex after it has been translocated down the
mRNA many codon sequences. The ribosome has constantly read the mRNA in the 5' ---> 3'
direction. The result is a growing chain of amino acids, all bonded together to make a
. polypeptide chain
When a codon with the nonsense sequence UAA, UAG (seen here), or UGA is exposed, that is a
signal that translocation is to stop. The stop codon is not bonded to a complementary
anticodon sequence on a tRNA. Rather, a protein known as a release factor binds at the A site.
.The release factor ultimately will help release the finished polypeptide chain in the next step

5. Release of polypeptide: The release factor (not shown in this diagram) prevents further
reading of the mRNA message. The polypeptide molecule is released from the ribosomal units.
The mRNA and the large and small ribosomal units are thus free to begin the translation
process again.

Transcription and translation


http://www.johnkyrk.com/DNAtranscription.html

http://www.johnkyrk.com/DNAtranslation.html

DNA replication

Replication fork

http://www.johnkyrk.com/DNAreplication.html

Mutations

Mutations are changes in DNA coding sequences.


Types of mutations include:
1. Frameshift mutations: involve a change in reading frame and are usually
severe, producing a completely nonfunctional protein.
2. Triplet repeat expansion mutations: e.g. GAC/glutamine repeats in
Huntingdons disease; GC rich regions; neurodegenerative disorders.
3. Point mutations:

Point mutations involve a single nucleotide, thus a single amino acid

Silent: A mutation that produces a functioning protein is called a silent


mutation.
Missense: A mutation that results in an amino acid substitution is
called a missense mutation.
Nonsense: A mutation that results in a stop codon so that incomplete
proteins are produced, it is called a nonsense mutation.

The Genetic Code


Triplet Codons and Corresponding Amino Acids
U

UUU
UUC
U

UUA

C
Phe

Leu

UCU

UAU

UCC

UAC

UCA

Ser

UAA

UUG

UCG

UAG

CUU

CCU

CAU

CUC
CUA

Leu

CCC
CCA

Pro

CAC
CAA

CUG

CCG

CAG

AUU

ACU

AAU

ACC

AAC

AUC

Ile

AUA
AUG

ACA
Met

GUU
G

GUC
GUA
GUG

Val

Thr

AAA

ACG

AAG

GCU

GAU

GCC
GCA
GCG

Ala

GAC
GAA
GAG

G
Tyr

STOP

His
Gln
Asn
Lys
Asp
Glu

UGU
UGC

Cys

UGA

STOP

UGG

Trp

CGU
CGC
CGA

Arg

CGG
AGU
AGC
AGA
AGG

Ser
Arg

GGU
GGC
GGA
GGG

Gly

Chromosomes

Chromosomal abnormalities

A translocation is when two


.chromosomes swap pieces of their arms
e.g. some Leukemias

An insertion is when one portion of a


. chromosome is inserted into another
Note that in this case, genetic material is
not swapped, it is just moved to another
.chromosome

Chromosomal abnormalities

A deletion is the loss


of a portion of a
.chromosome
e.g. Cri-du-chat
syndrome

An inversion is when a
segment of a
chromosome is broken in
two places and reversed
then put back into the
chromosome

A duplication is when a
segment of the DNA is
duplicated. (May be no
harmful phenotypic effect
present or may be harmful
like duplication of protooncogene expression)

Chromosomal abnormalities

Aneuploidy: is a change in the number of


chromosomes.e.g. Ch21 Trisomy in Downs syndrome

Cell cycle control and Mitosis

Proteins that promote cell growth

.Molecular cell biology, Lodish et al


.by W. H. Freeman and Company 2000

Cell cycle control animation

G1 = growth and preparation of the chromosomes for replication;


check cell size and nutrients
S = synthesis of DNA and duplication of centrosomes/centrioles
G2 = cell growth preparation for mitosis; check DNA integrity
.M = mitosis.; cell division into two daughter cells
/ http://nobelprize.org/educational_games/medicine/2001

Cell cycle control proteins Cdks and Cyclins

/http://nobelprize.org/educational_games/medicine/2001
p21, p27 and p53 and un-phosphorylated Rb cause cell cycle arrest

Mitosis: process by which somatic cells divide

http://www.johnkyrk.com/mitosis.html

Tumours and Cancer

Uncontrollable cell division and growth


Tumours: benign and malignant
Contact inhibition is lost
Anchorage dependence in normal cells is lost
Metastasis
Angiogenesis and hypoxia
Cells can become immortal; sometimes this is
associated with mutations in proto-oncogenes and
tumour suppressor genes.
Contribution of viral promoters at times
Multiple Hit Model

Meiosis
Meiosis is the type of cell division by which germ cells (eggs and
sperm) are produced. Meiosis involves a reduction in the amount of
.genetic material
Meiosis comprises two successive nuclear divisions with only one round
of DNA replication.
.Four stages can be described for each nuclear division

Meiosis differs from mitosis primarily because there are two cell divisions
.in meiosis, resulting in cells with a haploid number of chromosomes

Chromosomal abnormalities

Aneuploidy: is a change in the number of


chromosomes.e.g. Ch21 Trisomy in Downs syndrome

Meiosis

Meiosis

Chromosomal cross over and


recombination

Two genes independently


segregating

Mendelian Genetics

:Gregor Mendel
Austrian monk
Scientist
Pea farmer
Mendels experiments
refuted the blending
concept of inheritance.

Most traits are inherited


independently

Basic Terminology
Alleles-alternate forms of a gene.

Locus-alleles can be found on homologous chromosomes at a


particular location called a gene locus.

Terminology

Genotype
Phenotype
Dominant trait
Recessive trait
Zygote
Homozygous
Heterozygous

Punnet squares and test-crosses

F1
generation
ratios

.Phenotype

of offspring can reveal genotype of parents

Pedigree Trees
Obviously, it wouldnt be
ethical to do test-crosses
on humans! We record
human genetic
information in a pedigree.
A pedigree is a family tree
that follows inheritance of
a genetic trait for many
generations of relative.

Concepts in inheritance
Dominant and recessive: Huntingdons
(D); Cycstic fibrosis (R)
Co-dominance: ABO blood group
Incomplete dominance: pink flowers
Diseases:
Autosomal recessive
Autosomal dominant
Polygenic inheritance

Examples: Cystic
Fibrosis,
Phenylketonuria
(PKU)

Huntington Disease
and
Neurofibromatosis,
for example

Continuous variation and quantitative traits

Polygenic inheritance
Epistasis and Gene Modifiers

Concepts in inheritance
Polygenic inheritance
Pleiotropy: e.g. ion transmembrane channel and
muscular dystrophy
Epistasis : e.g. transcription factor control
Sex-linked inheritance: colour blindness, muscular
dystrophy
X-inactivation and barr bodies

Genes and phenotype

Environmental effects on
genetics

Chromosomal anomalies.
Environmental control of phenotype (heat
sensitive tyrosinase expression in Himalayan
rabbits cats white coat (+33C); tyrosinase
inactive, white pigment)
Gene therapy (SCID)
Sex determination and sex linked genes
(Interleukins and X-linked SCID).
Genetically modified organisms (Pectinase)
Ethical and safety issues in gene manipulation