Download Classical (Mendelian) Genetics

Classical (Mendelian) Genetics
Gregor Mendel
GENETICS
• The scientific study of heredity- how traits are
passed down to offspring
TRAIT---Specific characteristic ( blonde hair,
blue eyes)
GENE
• A hereditary unit consisting of a sequence of
DNA that occupies a specific location (LOCUS)
on a chromosome and determines a particular
characteristic in an organism.
(Genes undergo mutation when their DNA
sequence changes)
LOCUS (Loci plural)
• Is a location on a
chromosome where a
gene occurs
• Loci will be written as----6p21.2
• 6- chromosome number
• P- arm
• 21.2- distance from
centromere
Chromosome map
/ IDIOGRAM
• Detailed diagram of all
the genes on a
chromosome
GENOME
• is an organism's complete set of DNA,
including all of its genes. Each genome
contains all of the information needed to build
and maintain that organism. (more than 3
billion DNA base pairs in humans)
ALLELE
• Alternate forms of a gene/factor.
• Examples:
--brown eyes vs blue eyes
--blonde hair vs brown hair
--dimples vs no dimples
Types of alleles
• Dominant: An allele which is expressed
(masks the other).
• Recessive: An allele which is present but
remains unexpressed (masked)
PHENOTYPE vs GENOTYPE
• Genotype: combination of alleles an organism
has. (Ex- BB, Bb, or bb )
• Phenotype: How an organism appears.
(Ex- brown hair, blonde hair )
GENOTYPES
• Homozygous: Both alleles for a trait are the
same. (BB- homozygous dominant, bb
homozygous recessive)
• Heterozygous: The organism's alleles for a
trait are different. (Carrier of the recessive
allele) Bb
GREGOR MENDEL
• An Austrian Monk (1822-1884)
• Developed these principles without ANY scientific
equipment - only his mind.
• Tested over 29,000 pea plants by crossing various
strains and observing the characteristics of their
offspring.
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)
GREGOR MENDEL
• Studied the
following
characteristics:
1. Pea color
(Green, yellow)
2. Pea shape
(round, wrinkled)
3. Flower color
(purple, white)
4. Pod shape
( inflated,
constricted)
5. Pod color
(green, yellow)
6. Plant height (tall,
short)
7. Flower position
(axial, terminal)
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.
Mendel’s Experiments
Mendel noticed that some plants always produced offspring that had a form of a
trait exactly like the parent plant. He called these plants “purebred” plants. For
instance, purebred short plants always produced short offspring and purebred tall
plants always produced tall offspring.
Mendel called these the P 1 generation. (pure bred, parental)
X
Purebred Short Parents
Short Offspring
X
Purebred Tall Parents
Tall Offspring
Mendel’s First Experiment
Mendel crossed purebred plants with opposite forms of a trait. He called these plants
the parental generation , or P generation. For instance, purebred tall plants were
crossed with purebred short plants.
X
Parent Short
Offspring Tall
Parent Tall
P generation
F1 generation
P generation
Mendel observed that all of the offspring grew to be tall plants. None resembled
the short short parent. He called this generation of offspring the first filial , or F1
generation, (The word filial means “son” in Latin.)
Mendel’s Second Experiment
Mendel then crossed two of the offspring tall plants produced from his first
experiment.
Parent Plants
Offspring
X
Tall
F1 generation
3⁄4 Tall & 1⁄4 Short
F2 generation
Mendel called this second generation of plants the second filial, F2, generation.
To his surprise, Mendel observed that this generation had a mix of tall and short
plants. This occurred even though none of the F1 parents were short.
TERMS TO KNOW
• MONOHYBRID CROSS- cross using only one trait
• SELF CROSS- (SELF FERTILIZATION)- produce offspring
asexually
• P1 GENERATION-- parents- usually pure bred
• F1 GENERATION- 1st set of offspring (1st family)
• F 2 GENERATION- 2nd set of offspring (2nd family)
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
Developed 3 laws
LAW OF DOMINANCE- one allele always shows
over the other
LAW OF INDEPENDENT ASSORTMENT- states that
each pair of genes (chromosomes) separate
independently of each other in the production of
sex cells. (example– you could have brown hair
and blue eyes)
LAW OF SEGREGATION-
Mendel’s Law of Segregation
Mendel’s first law, the Law of Segregation, has three parts. From his
experiments, Mendel concluded that:
1. Plant traits are handed down through “hereditary factors” in the sperm
and egg.
2. Because offspring obtain hereditary factors from both parents, each plant must
contain two factors for every trait.
3. The factors in a pair segregate (separate) during the formation of sex
cells, and each sperm or egg receives only one member of the pair.
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
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' Xchromosome).
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)
• Definitiongenes 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 question- where
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.