Transcript GeneticExceptionsx

The likelihood that an event will occur.
•No chance of event probability = 0
(e.g. chance of rolling 8 on a six-sided die)
•Event always occurs probability = 1
(chance of rolling 1,2,3,4,5,or 6 on a six-sided die)
The probabilities of all the possible events add up to 1.
# on die
probability
1
1/6
2
1/6
3
1/6
4
1/6
5
1/6
6
1/6
The probability of an event
= # of chance of event
total possible events
The product rule sates:
The probability of independent events is calculated by
multiplying the probability of each event.
In two rolls of a die, the chance of rolling the number 3 twice:
Probability of rolling 3 with the first die
= 1/6
Probability of rolling 3 with the second die = 1/6
Probability of rolling 3 twice = 1/6 x 1/6 or 1/36
The probability of dependent events is calculated
by adding the probability of each event.
In one roll of a die, what is the probability of rolling either
the number 5 or an even number?
Probability of rolling the number 5
= 1/6
Probability of rolling an even number = 3/6
Probability of rolling 5 or an even number = 1/6 + 3/6 or 4/6
What is the chance of an
offspring having the
homozygous recessive
genotype when both parents
are doubly heterozygous?
Parents are heterozygous for a trait, R.
What is the chance that their child is carries
at least one dominant R allele?
Probability of child carrying RR = 1/4
Probability of child carrying Rr = 1/2
Probability of child carrying R_ = 1/4 + 1/2 = 3/4
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Hemophilia was one of the first pedigree charts
to trace an inherited illness
Albinism: homozygous recessive lacks an
enzyme necessary to manufacture the pigment
melanin
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Pale hair and skin
Autosomal recessive
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Most of the traits Mendel studied were on
different genes but some were actually on the
same chromosome but at opposite ends
Genes located close to each other on the same
chromosome usually do not separate during
meiosis, they are linked
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Is the term indicating
that two genes are not
transmitted
independently.
Why?
 Two genes physically
near each other on a
chromosome will not
assort randomly in
meiosis.
Types of gametes from a parent
heterozygous for two genes?
Unlinked :
4 type of gametes
PL, Pl, pL, pl
Tightly linked:
2 types of gametes
PL and pl
NOTE for LINKAGE: which two types are observed
(PL and pl OR Pl and pL) depends on which alleles are
on the same chromosome in the parent!
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A linkage map is a diagram indicating the relative distance
between genes.
1% recombination = 1 map unit = 1 centiMorgan (cM)
Map distances are additive.
X and Y
X and Z
Y and Z
% recombination
between genes
10
4
6
X
Z
4 cM
Y
6 cM
10 cM
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j, k
k, l
j, m
l, m
12%
6%
9%
15%
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a, c
b, c
a, d
b, d
10%
24%
30%
16%
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Mutations:
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Changes in the DNA sequence that affect genetic
information
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Two type of mutations:
 Chromosomal (changes in chromosome)
 Gene (changes in a single gene)
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Affect only one nucleotide
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Occur at a single point in the DNA sequence
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Substitution (CAT  RAT)
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Point mutation that involves the insertion or
deletion of a nucleotide
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Changes the reading frame (read in 3s)
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Much bigger affect on the DNA sequence
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Insertion
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THE FAT CAT ATE THE RAT
THE FAT CAT EAT ETH ERA T
Deletion
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THE FAT CAT ATE THE RAT
THF ATC ATA TET HER AT
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Chromosomal mutations involves changes in
the number or structure of chromosomes
Types of Chromosomal Mutations:
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Inversion (ABC*DEF  AED*CBF)
Deletion (ABC*DEF  AC*DEF)
Duplication (ABC*DEF  ABBC*DEF)
Translocation
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Monosomy-missing one chromosome (45)
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Trisomy-one extra chromosome (47)
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Haploid – one set of chromosomes (23)
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Ex: gametes (egg or sperm)
Diploid – two sets of chromosomes (46)
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Ex: Down’s Syndrome (trisomy 21)
Ex: body cells
Polyploid – multiple sets of chromosomes
Some allele combinations are lethal.
Mexican hairless dogs result from a mutation in a
gene that shows lethality
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hh
hairy
the wild type trait
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Hh
hairless
one mutation present
creates a visible phenotype
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HH
dies
two mutation are lethal
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Lethal is deadly, so any genotype (allele
combination) that causes the death of an
individual is literally lethal
In a population and evolutionary sense
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It causes death before the individual can reproduce
This prevents passage of genes to the next
generation
 Huntington’s disease- fatal in middle age, is lethal to the
individual, not the population
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In humans, early acting lethal alleles cause
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Spontaneous abortions
When a man and a woman each carry a recessive
allele (lethal) each pregnancy has a 25% chance of a
miscarriage
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A person only has two alleles for any
autosomal gene, but
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A gene may exist in more than two allelic forms in a
population, because
 Genes can mutate in many ways at any nucleotide in their
DNA sequence
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Different allele combinations produce
variations in phenotype
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Phenylketonuria (PKU) is an inborn error in metabolism
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When the enzyme is absent: mental retardation
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The amino acid phenylalanine that the enzyme normally breaks
down builds up in the brain cells causing mental retardation
 If the individual is placed on a special diet extremely low in
phenylalanine from birth until 8 years of age or longer, it is possible
to allow for normal brain development
 There are more than 300 mutant alleles for this gene to combine to
form four basic phenotypes
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Classic PKU: mental retardation
Moderate PKU
Mild PKU
Excreting excess of the amino acid in the urine, no symptoms
indicates the heterozygous phenotype is distinct
from either homozygous phenotype.
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The heterozygous phenotype is typically
intermediate to the homozygous phenotype
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On the whole body level, Tay-Sachs disease displays complete
dominance because the heterozygote is a carrier.
If phenotype is based on the enzyme level, then the
heterozygote is between the homozygote dominant (full
enzyme level) and homozygote recessive (no enzyme)
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This example is more
obvious.
The pink flower is
due to an
intermediate amount
of pigment
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Familial hypercholesterolemia (FH) shows
incomplete dominance on both the molecular
and whole-body levels
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A person with two-disease causing alleles lacks receptors on
liver cells that take up cholesterol from the bloodstream
 Die as children of a heart attack
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A person with one-disease allele has half the normal number of
receptors
 May suffer heart attacks in middle age
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Two wild type alleles has the normal receptors
 Do not develop this inherited form of heart disease
The ABO gene encodes a cell surface
protein.
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Allele A makes A protein
Allele B makes B protein
Allele O makes no protein
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(missing one DNA nucleotide)
Alleles A and B can be present on
the cell surface at the same time.
 Alleles A and B are codominant.
 Allele O is recessive to both A
and B alleles.
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when one gene masks
or affects the
expression of a second
gene.
Is a result of two interacting
genes: the I and H genes
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H protein attaches the A
or B protein to the cell
surface.
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The normal H allele encodes for an enzyme that inserts a
sugar molecule, antigen H, onto a glycoprotein on the
surface of an immature RBC
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Fucosyltranserase 1 The H gene is called FUT1
The recessive h allele produces an inactive form of the
enzyme-no insertion
The A and B antigens are attached to the H antigen
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Therefore as long as there is at least one H allele pr4esent the
ABO genotype dictates the ABO blood type
hh genotype there is no H antigen and A and B antigens cannot
attach: The person has O blood based on phenotype but, may
have any ABO genotype
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A gene does not act alone at times
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Nutrition
Toxic exposures
Illnesses
Actions of other genes
 Influence the expression of most genes
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Two individuals who have the most severe
genotype for CF and one is much sicker
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She is sicker because she has also inherited genes
predisposing her to develop asthma and respiratory
allergies
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Two terms you need to know
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Penetrance
 Refers to the all or none expression of a genotype
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Expressivity
 Refers to severity or extent
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This cause Mendelian traits and illnesses to
have distinct phenotypes
Penetrant allele combination
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Huntington disease: all will develop symptoms if
they live long enough
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Incomplete penetrant occurs if some
individuals do not express the phenotype
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No symptoms
 Polydactyly
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A phenotype is variably expressive if
symptoms vary in different people
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Polydactyly
Familial hypercholesterolemia
 FH heterozygote can develop heart disease due to high
serum cholesterol in middle age, but, healthy diet and
exercise can delay symptoms
A phenotype that varies in intensity shows
variable expressivity.
FF or Ff
all show mild, moderate or
profound deafness
Incomplete penetrance
Occurs when the disease phenotype is not always
observed among individuals carrying the
disease-associated genotype.
DD or Dd
80% polydactyly
DD or Dd
20% no polydactyly
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One gene controls or
influences the
expression of many
symptoms
in a disorder. These
symptoms may be
variably expressed.
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Porphyria variegata an
autosomal dominant,
inborn error of
metabolism
Read page 98 about the
royal family of King
George III
Photo © North Wind Picture Archives
A trait caused by the environment that
mimics an inherited condition.
Exposure to teratogens
 Thalidomide causes limb defects akin to rare
inherited phocomelia.
Infection
 Rubella in pregnant mothers causes deafness
mimicking inherited forms of deafness.
Different genes can produce identical
phenotypes.
Individuals with identical phenotypes
may reflect different genetic causes.
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Deafness
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Albinism
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Cleft palate
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Poor blood clotting
AUTOSOMAL RECESSIVE
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Lack of pigment in
skin, hair, and nails
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Excess mucus in
lungs, digestive tract,
liver
Increased
susceptibility to
infections
Death in childhood
unless treated
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Accumulation of
galactose (sugar) in
tissues
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Mental retardation
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Eye and liver damage
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Accumulation of
phenylalanine in
tissues
Lack of normal skin
pigment
Mental retardation
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Lipid accumulation in
brain cells
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Mental deficiency
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Blindness
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Death in early
childhood
AUTOSOMAL DOMINANT
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dwarfism
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Mental deterioration
and uncontrollable
movements
Appears in middle
age
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Excess cholesterol in
blood
Heart disease
CODOMINANT ALLELES
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Sickled red blood cells
Damage to many
crisis
Mutation in the
coding for
hemoglobin
SEX-LINKAGE
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Inability to
distinguish certain
colors
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A protein necessary
for normal blood
clotting is missing
Can be treated with
injections
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Progressive
weakening of the
skeletal muscle
CHROMOSOMAL
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Trisomy 21
Mild to severe
retardation
Increased
susceptibility to
disease
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Female with XO
No secondary sex
characteristics
Unusual physical
stature
sterile
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Male with XXY
No secondary sex
characteristics
Slight mental
retardation
sterile
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Dominant/Recessive
Incomplete
Dominance
Codominance
Sex-Linkage
Chromosome
Mapping
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Pedigree Analysis
Probability
Chi-square analysis
Mutations
Epistasis