Download GENETICS

GENETICS
DR. PETER VICKERS
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WHAT ARE GENES?
 GENES ARE SECTIONS OF DNA CARRIED ON
OUR CHROMOSOMES WHICH CONTAIN
PARTICULAR SETS OF INSTRUCTIONS
RELATED TO OUR GROWTH, DEVELOPMENT,
REPRODUCTION, FUNCTIONING AND AGING
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SOME DEFINITIONS
 DNA = Deoxyribonucleic Acid – makes up the double helix
 RNA = Ribonucleic Acid – along with mRNA (below)
determines the amino acid composition of proteins, which, in
turn determines the function of the protein, and therefore the
function of that particular cell
 mRNA = messenger Ribonucleic Acid
 Chromosome – see later slide
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CHROMOSOME
• A chromosome is a complicated strand of DNA and
protein
• Each chromosome is made up of 2 chromatids joined
by a centromere
• Each cell in our body which has a nucleus contains,
within its genes, all the genetic information to make an
entire human being
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NUCLEOTIDES
• Consist of 3 molecules:
• 1. Deoxyribose - a 5 carbon cyclic sugar
• 2. Phosphate - inorganic negatively-charged
molecule
• 3. Base - a nitrogen-carbon ring structure
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BASES
• There are 4 different bases found in DNA
• adenine (A)
• thymine (T)
• guanine (G)
• cytosine (C)
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BASES & DOUBLE HELIX
• The order of the bases along the length of the DNA
molecule provides the variation that allows for
information storage
• The golden rule:
• adenine always pairs with thymine
• guanine always pairs with cytosine
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CHROMOSOMES
• The nuclear DNA of eukaryotes is associated with protein
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molecules called HISTONES
Together, these 2 components make up the
NUCLEOSOMES contained within the cell nucleus.
This nucleic acid-histone complex is known as CHROMATIN
Chromatin is tightly folded because the DNA molecules are
very long would not fit in the cell otherwise
Unravelled it would stretch to the moon and back about
8,000 times
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CHROMOSOMES
• Each chromosome is made up of 2 chromatids
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joined by a centromere
In most humans, each nucleated body cell has 46
chromosomes, arranged in 23 pairs
One pair determines the sex of a person
Females have a matched homologous pair of X
chromosomes
Males have an unmatched heterologous pair - one X
and one Y chromosome
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• The remaining 22 pairs of chromosomes are known
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as AUTOSOMES (which determine physical/body
characteristics and others)
These are homologous since both members of the
pair are usually identical in shape and size
The position a gene occupies on a chromosome is
called a LOCUS
There are different loci for colour, height, etc.
Genes that occupy corresponding loci are called
ALLELES
An allele determines an alternative form of the
same characteristic
GENES
• A person with a pair of identical alleles for a
particular gene locus is HOMOZYGOUS for that gene
locus
• One with a dissimilar pair is HETEROZYGOUS
• A DOMINANT GENE is one which exerts its effects
when it is present on only one of the chromosomes
• A RECESSIVE GENE has to be present on both
chromosomes to manifest itself physically
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NUCLEIC ACIDS
• Nucleic acids have 2 major functions:
• 1. The direction of all protein synthesis
• 2. The accurate transmission of this information
from one generation to the next, and from one cell
to its daughter cells
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PROTEIN SYNTHESIS
• Cells make proteins by translating the genetic information
encoded in DNA
• The genetic information in a region of DNA is copied to
produce a specific molecule of RNA
• Through a complex series of reactions, the information
contained in RNA is translated into a corresponding
specific sequence of amino acids in a newly produced
protein molecule
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PROTEIN SYNTHESIS
• There are, therefore, 2 principal steps in protein
synthesis:
• 1. Transcription
• 2. Translation
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MEERA NAAM PETER HAI
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MY NAME IS PETER
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TRANSCRIPTION
• The process by which genetic information encoded
in DNA is copied by a strand of mRNA
• By using a specific portion of the cell’s DNA as a
template, the genetic information stored in the
sequence of nitrogenous bases of DNA is rewritten
so that the same information appears in the
nitrogenous bases of mRNA
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• CYTOSINE in template = GUANINE in mRNA
• GUANINE in template = CYTOSINE in mRNA
• THYMINE in template = ADENINE in mRNA
• ADENINE in template = URACIL (U) in mRNA
• E.g. if DNA has base sequence AGGCAGTGC
• Then mRNA has base sequence UCCGUCACG
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key
guanine
cytosine
adenine
thymine
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TRANSLATION
• The process by which information in the nitrogenous base
of mRNA is used to specify the amino acid sequence of a
protein.
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SUMMARY
• As each ribosome moves along the mRNA strand, it
‘reads’ the information coded in the mRNA and
synthesises a protein according to that information
• The ribosome synthesises the protein by translating
the codon sequence into an amino acid sequence
• Protein synthesis progresses at the rate of about 15
amino acids per second
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• As the ribosome moves along the mRNA strand, and
before it completes translation of that gene, another
ribosome may attach itself and begin translation of
the same mRNA strand
• Several ribosomes moving simultaneously in tandem
along the same mRNA molecule permit the
translation of a single mRNA strand into several
identical proteins simultaneously
• Thus we can define a GENE as a group of
nucleotides on a DNA molecule that serves as the
master mould for manufacturing a specific protein
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• Genes average about 1,000 pairs of nucleotides
which appear in a specific sequence on the DNA
molecule
• No two genes have exactly the same sequence of
nucleotides, and this is the key to heredity
• c) each gene is responsible for making a particular protein,
as follows:
transcription
•
•
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DNA
translation
RNA
protein
DNA
double
helix
DNA
coding
strand
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transcription
Messenger
RNA
translation
protein
The flow of information from DNA to RNA to protein
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CELL DIVISION
• In order for the body to grow and to replace cells
which have died, cells must be able to reproduce
themselves
• In some organisms, this can occur by simple
fission
• The nucleus in a single cell becomes elongated
and then divides to form 2 nuclei in one cell
• The cytoplasm then divides in between the 2
nuclei to form 2 daughter cells, each with its own
nucleus
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FUSION OF THE GAMETES
• When the gametes, each with 23 chromosomes,
fuse together, a cell known as a ZYGOTE with 23
paired chromosomes (i.e. 46 in all) is formed
• One chromosome from each pair comes from the
mother, and one from the father
• The zygote cell then divides by mitosis many times
to form the embryo
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MENDELIAN GENETICS
• 1865 - Gregor Mendel - a monk living in Brno
• Wanted to produce the finest peas
• Studied them extensively
• Introduced 3 novel (for that time) approaches to
study:
– Not only observed, but experimented
– Then he counted (statistics)
– Ensured original parental stocks were pure
breeding stocks
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• Mendel demonstrated that members of a pair of ALLELES
separate clearly during meiosis
• We all possess a pair of genes (alleles) at any one LOCUS,
but we can only pass on ONE of these genes to our child
FATHER
Aa
•
AB
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Ab
MOTHER
Bb
aB
ab
Another way of representing genetic inheritance
is by means of a PUNNET SQUARE
Aa
AB
aB
Bb
Ab
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ab
• The previous diagram explains Mendel’s FIRST LAW
• This is that the father can pass either gene A or gene a,
and the mother gene B or gene b
• But each child can only inherit either gene A or gene a
and gene B or gene b
• Therefore statistically, there is a 1 in 4 (1:4) chance
that any child of these two parents will have genes AB,
Ab,aB or ab
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MENDEL’S SECOND LAW
• Members of different pairs of alleles sort
independently of each other during gametogenesis
• Each member of a pair of alleles may occur randomly
with either member of another pair of alleles
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DOMINANCE
• At each locus, the 2 alleles can be either DOMINANT or
RECESSIVE
• Dominant genes are always expressed by the next
generation if they are passed on
• Recessive genes are only expressed if they share a locus
with another recessive gene
• Note: in genetic representations, dominant genes are
always given capital letters, whilst recessive genes are
given lower case letters
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• Look at our Punnet Square again
Aa
AB
aB
Bb
Ab
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ab
•75% of the offspring carry at least one dominant gene,
and 25% carry only recessive genes.
•Therefore, 75% will express a dominant gene, and
25% a recessive gene.
AUTOSOMAL DOMINANT INHERITANCE
• If a dominant gene is one that causes a medical disorder,
for example Huntington’s Disease or Neurofibromatosis,
then there will be a 50% risk of having that medical
condition
• There will thus be a 50% of not having the condition
• This mode of inheritance is known as Autosomal Dominant
Inheritance
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AUTOSOMAL DOMINANT DISORDERS
• Apart from the odd disorder, such as Huntington’s
Disease, Autosomal Dominant disorders are
generally not as fatal or as severe as Autosomal
Recessive disorders
• Why Not?
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AUTOSOMAL RECESSIVE INHERITANCE
Aa
AB
aB
Ba
Aa
aa
Returning to the Punnet Square - if the 2 recessive
genes (aa) are coded for the same medical disorder,
then the chances at each pregnancy of having an
affected child are:
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• For an affected child = 25% (1:4)
• For a carrier = 50% (1:2)
• For a child who is neither affected nor a carrier =
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25% (1:4)
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Remember that these odds occur for each pregnancy, so
you could have:
4 children and have 1 affected, 2 carriers, and 1
unaffected
Or 4 carriers
Or 3 affected and 1 carrier
And so on ...
The odds are the same for each child!
AUTOSOMAL RECESSIVE DISORDERS
• Examples of Autosomal Recessive disorders are:
• Cystic Fibrosis
• Thalassaemia
• Severe Combined Immunodeficiency (SCIDS)
• Spinal Muscular Atrophy
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X-LINKED DISORDERS
• As well as autosomal inheritance, we can inherit
disorders via the sex chromosomes
• For a girl, these are XX
• For a boy they are XY
• The main role of these chromosomes is to
determine the sex of a baby
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MOTHER XX
FATHER XY
•
• XX
XY
XX
XY
• What are the chances of a couple having a boy or a
girl?
• The chances are 50% for a girl and 50% for a boy
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• Suppose the mother carried an abnormal, recessive
gene on one of her X chromosomes – here denoted
by the green ‘X’
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MOTHER XX
• XX
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FATHER XY
XY
XX
XY
• The Y chromosome is unable to ‘block’ any of the
genes on the mother’s chromosome
• Therefore the possibilities in any one child are:
• 1. One girl would not be a carrier or be affected
• 2. One girl would be a carrier, but not affected
• 3. One boy would not be a carrier or affected
• 4. One boy would be affected
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• Thus we can say, with regard to X-linked disorders:
• 1. Only boys are affected, and there is a 50%
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chance that they will be affected, but 100%
chance that they will not be carriers
2. No girls are affected, but there is a 50% chance
that they will be a carrier
Examples are:
Haemophilia
Duchenne Muscular Dystrophy
X-linked Agammaglobulinaemia
Red-Green Colour Blindness
HLA TYPING - TT
• * Parents are 1st. Cousins
• Father
A9,24
•
A11
• Mother
A29
•
A9,24
• TT
A11
•
A2
• FT (sister) A9,24
•
A2
• RT (sister) A11
•
A2
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B40
B35
B40
B40
B35
B40
B40
B40
B35
B40
DR2
DR2
DR2
DR2
DR2
DR2
DR2
DR2
DR2
DR2
HLA TYPING - GO
• * Parents say they are not related
• Father
A1
A11
•
• Mother
• GO
•
50
A1
A 24
A11
B8
B35
B8
B13
B35
A1
DR3
DR7
DR3
DR7
DR7
B8
DR3
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chromosomes. (n.d.). The American Heritage® Science Dictionary. Retrieved
August 26, 2014, from Dictionary.com website:
http://dictionary.reference.com/browse/chromosomes
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