Download Classical (Mendelian) Genetics

Classical (Mendelian)
Genetics
Gregor Mendel
Vocabulary
•
•
•
•
•
Genetics: The scientific study of heredity
Allele: Alternate forms of a gene/factor.
Genotype: combination of alleles an organism has.
Phenotype: How an organism appears.
Dominant: An allele which is expressed (masks the
other).
• Recessive: An allele which is present but remains
unexpressed (masked)
• Homozygous: Both alleles for a trait are the same.
• Heterozygous: The organism's alleles for a trait are
different.
History
• Principles of genetics were developed
in the mid 19th century by Gregor
Mendel an Austrian Monk
• Developed these principles without
ANY scientific equipment - only his
mind.
• Experimented with pea plants, by
crossing various strains and observing
the characteristics of their offspring.
• Studied the following characteristics:
– Pea color (Green, yellow)
– Pea shape (round, wrinkled)
– Flower color (purple, white)
– Plant height (tall, short)
MONOHYBRID CROSS- cross
fertilizing two organisms that differ
in only one trait
SELF-CROSS- allowing the organism
to self fertilize (pure cross)
MENDEL’S CROSSES
Started with pure
plants ( P1)
Then made a hybrid
of two pure traits
P1 X P1
• Made the following
observations (example
given is pea shape)
• When he crossed a round
pea and wrinkled pea, the
offspring (F1 gen.) always
had round peas.
• When he crossed these
F1 plants, however, he
would get offspring which
produced round and
wrinkled peas in a 3:1
ratio.
Laws of Inheretance
• Law of Segregation: When gametes
(sperm egg etc…) are formed each
gamete will receive one allele or the other.
• Law of independent assortment: Two or
more alleles will separate independently of
each other when gametes are formed
Punnett Squares
• Genetic problems can be easily solved
using a tool called a punnett square.
– Tool for calculating genetic probabilities
A punnett square
Monohybrid cross
(cross with only 1 trait)
• Problem:
• Using this is a several step process, look
at the following example
– Tallness (T) is dominant over shortness (t) in
pea plants. A Homozygous tall plant (TT) is
crossed with a short plant (tt). What is the
genotypic makeup of the offspring? The
phenotypic makeup ?
Punnet process
1. Determine alleles of
each parent, these
are given as TT, and
tt respectively.
2. Take each possible
allele of each parent,
separate them, and
place each allele
either along the top,
or along the side of
the punnett square.
Punnett process continued
• Lastly, write the letter
for each allele across
each column or down
each row. The
resultant mix is the
genotype for the
offspring. In this case,
each offspring has a Tt
(heterozygous tall)
genotype, and simply a
"Tall" phenotype.
Punnett process continued
• Lets take this a step
further and cross these
F1 offspring (Tt) to see
what genotypes and
phenotypes we get.
• Since each parent can
contribute a T and a t to
the offspring, the
punnett square should
look like this….
Punnett process continued
• Here we have some more
interesting results: First
we now have 3
genotypes (TT, Tt, & tt) in
a 1:2:1 genotypic ratio.
We now have 2 different
phenotypes (Tall & short)
in a 3:1 Phenotypic
ratio. This is the
common outcome from
such crosses.
Dihybrid crosses
• Dihybrid crosses are made when phenotypes
and genotypes composed of 2 independent
alleles are analyzed.
• Process is very similar to monohybrid crosses.
• Example:
– 2 traits are being analyzed
– Plant height (Tt) with tall being dominant to short,
– Flower color (Ww) with Purple flowers being dominant
to white.
Dihybrid cross example
• The cross with a pure-breeding (homozygous)
Tall,Purple plant with a pure-breeding Short,
white plant should look like this.
F1 generation
Dihybrid cross example continued
• Take the offspring and cross them since they are
donating alleles for 2 traits, each parent in the f1
generation can give 4 possible combination of alleles.
TW, Tw, tW, or tw. The cross should look like this. (The
mathematical “foil” method can often be used here)
F2 Generation
Dihybrid cross example continued
• Note that there is a 9:3:3:1
phenotypic ratio. 9/16
showing both dominant traits,
3/16 & 3/16 showing one of the
recessive traits, and 1/16
showing both recessive traits.
• Also note that this also
indicates that these alleles are
separating independently of
each other. This is evidence of
Mendel's Law of independent
assortment
PROBABILITY
• Definition- Likelihood that a specific
event will occur
• Probability =
number of times an event happens
number of opportunities for event
to happen
What if you don’t know the
GENOTYPE?
Perform a TEST CROSS- cross with a
homozygous recessive individual
If no recessive traits appear than unknown
individual was HOMOZYGOUS DOMINANT
TEST CROSS
• If the unknown individual was
heterozygous than 50% of the offspring
should have the recessive phenotype.
INCOMPLETE DOMINANCE
• When neither allele is completely
recessive
• Example RR ---- red roses
rr---------- white roses
Rr-------pink roses
In the HETEROZYGOUS
individual both alleles are still
visible – but not fully visible
Other Factors: Incomplete Dominance
• Some alleles for
a gene are not
completely
dominant over
the others. This
results in
partially masked
phenotypes
which are
intermediate to
the two
extremes.
Other Factors: Continuous Variation
• Many traits
may have a
wide range of
continuous
values. Eg.
Human height
can vary
considerably.
There are not
just "tall" or
"short" humans
CODOMINANCE
When the HETEROZYGOUS INDIVIDUAL
fully shows both alleles.
Example is blood type
Blood Type A is dominant
Blood Type B is dominant
Blood Type O is recessive to both
A and B
Blood Type AB- is heterozygous for A and B
Multiple Alleles
• Phenotypes are controlled by more than 2 variances for a trait
• ABO Blood typing
– Humans have multiple types of surface antigens on RBC's
– The nature of these surface proteins determines a person's
Blood Type.
– There are 3 alleles which determine blood type IA, IB, or IO. This
is referred to as having multiple alleles
– Human blood types are designated as A, B or O.
• Type A denotes having the A surface antigen, and is denoted by IA
• Type B denotes having the B surface antigen, and is denoted by IB
• Type O denotes having neither A or B surface antigen, and is
denoted by IO
– There are several blood type combinations possible
•
•
•
•
A
B
AB (Universal recipient)
O (Universal donor)
Punnett Square for blood typing
A
B
O
A
O
AB
BO
AO
OO
Blood & Immunity
• A person can receive blood only when the donor's blood type does
not contain any surface antigen the recipient does not. This is
because the recipient has antibodies which will attack any foreign
surface protein.
• Thus, Type AB can accept any blood types because it will not attack
A or B surface antigens. However, a type AB person could only
donate blood to another AB person. They are known as Universal
Recipients.
• Also, Type O persons are Universal donors because they have NO
surface antigens that recipients' immune systems can attack. Type
O persons can ONLY receive blood from other type O persons.
• There is another blood type factor known as Rh.
• People are either Rh+ or Rh- based on a basic dominant/recessive
mechanism.
• Not usually a problem except with pregnancy.
• It is possible that an Rh- mother can carry an Rh+ fetus and develop
antibodies which will attack & destroy the fetal blood
• This usually occurs with 2nd or 3rd pregnancies, and is detectable
and treatable.
Other Factors
• Gene interaction:
– Many biological pathways are governed by multiple
enzymes, involving multiple steps.(Examples the
presence of a HORMONE) If any one of these steps
are altered. The end product of the pathway may be
disrupted.
• Environmental effects:
– Sometimes genes will not be fully expressed owing to
external factors. Example: Human height may not be
fully expressed if individuals experience poor
nutrition.
Chapter 12--Sex Linkage
• All chromosomes are homologous except on
sex chromosomes.
• Sex chromosomes are either X or Y.
• If an organism is XX, it is a female, if XY it is
male.
• If a recessive allele exists on the X
chromosome. It will not have a corresponding
allele on the Y chromosome, and will therefore
always be expressed
PEDIGREE ANALYSIS
 is an important tool for studying inherited
diseases
 uses family trees and information about
affected individuals to:
figure out the genetic basis of a disease or
trait from its inheritance pattern
predict the risk of disease in future offspring
in a family (genetic counseling)
How to read pedigrees
Basic patterns of inheritance
1. autosomal, recessive
2. autosomal, dominant
3. X-linked, recessive
4. X-linked, dominant (very rare)
How to read a pedigree
Sample pedigree - cystic fibrosis
male
affected individuals
female
Autosomal dominant pedigrees
1. The child of an affected parent has a 50% chance of inheriting the
parent's
mutated allele and thus being affected with the disorder.
2. A mutation can be transmitted by either the mother or the father.
3. All children, regardless of gender, have an equal chance of
inheriting the mutation.
4. Trait does not skip generations
Autosomal dominant traits
There are few
autosomal dominant
human diseases
(why?), but some rare
traits have this
inheritance pattern
ex. achondroplasia
(a sketelal disorder
causing dwarfism)
AUTOSOMAL RECESSIVE
1. An individual will be a "carrier" if they
posses one mutated allele and one normal
gene copy.
2. All children of an affected individual will
be carriers of the disorder.
3. A mutation can be transmitted by either
the mother or the father.
4. All children, regardless of gender, have
an equal chance of inheriting mutations.
5. Tends to skip generations
Autosomal recessive diseases in humans
Most common ones
• Cystic fibrosis
• Sickle cell anemia
• Phenylketonuria (PKU)
• Tay-Sachs disease
Autosomal Recessive
X-Linked Dominant
1. A male or female child of an affected
mother has a 50% chance of inheriting the
mutation and thus being affected with the
disorder.
2. All female children of an affected father
will be affected (daughters possess their
fathers' X-chromosome).
3. No male children of an affected father will
be affected (sons do not inherit their
fathers' X-chromosome).
X-LINKED Recessive
1. Females possessing one X-linked
recessive mutation are carriers
2. All males possessing an X-linked
recessive mutation will be affected (why?)
3. All offspring of a carrier female have a
50% chance of inheriting the mutation.
4. All female children of an affected father
will be carriers (why?)
5. No male children of an affected father will
be affected
Sex linkage example
• Recessive gene for white eye
color located on the Xw
chromosome of Drosophila.
• All Males which receive this
gene during fertilization (50%)
will express this.
• If a female receives the Xw
chromosome. It will usually
not be expressed since she
carries an X chromosome with
the normal gene
Human Sex Linkage
• Hemophilia:
– Disorder of the blood
where clotting does not
occur properly due to a
faulty protein.
– Occurs on the X
chromosome, and is
recessive.
• Thus a vast majority of
those affected are males.
– First known person known
to carry the disorder was
Queen Victoria of England.
Thus all those affected are
related to European
royalty.
LINKAGE GROUPS (pg 222)
• Definition- genes that are located on the
same chromosome.
• Discovered by Thomas Hunt Morgan.
Made a dihybrid cross with heterozygous
fruit flies ( Gray body and Long wings)
• GgLl x GgLl = predicted a 9:3:3:1 ratio
• What ratio did he get?
Answer
• He only got two combinations.
• Gray body with long wings - DOMINANT
• white body with short wings- RECESSIVE
• And they were in a 3:1 ratio just like a
standard MONOHYBRID cross.
• Conclusion– these GENES must be on the
same chromosome.
Further studies of Morgan
Wanted to find out which traits were linked
together on the same chromosome.
Linked many traits together (remember that
fruit flies have only 4 chromosomes)
During his many linkage studies
found some mutations
• While working with the gray body and long
wing linkage.
• Occasionally he had some flies come out
Gray body with short wings and
• White body with long wings
• How could this be?
CROSSING OVER- forms new
genetic combinations
Long wings
White body
Short wings
Gray body
Long wings
White body
Short wings
Gray body
CHROMOSOME MAPPING
New questionwhere are the
genes located on a
chromosome?
How far apart are the
genes on a
chromosome?
Using the rate of CROSSING
OVER to determine location.
CHROMOSOME MAPPING
• The PERCENTAGE of crossing over is
equal to ONE MAP UNIT on a
chromosome.