Download Mendelian Genetics I

Human Genetics
Mendelian Genetics
Inheritance
 Parents and offspring often
share observable traits.
 Grandparents and
grandchildren may share
traits not seen in parents.
 Why do traits disappear in
one generation and
reappear in another?
 Why do we still keep
talking about Mendel and
his peas?
Darwin Prior to Mendel
 Scientists looked for rules to explain continuous
variation.
 The “blending” hypothesis: genetic material from
the two parents blends together
 Head size, height, longevity – all continuous
variations - support the blending hypothesis
 The “particulate” hypothesis: parents pass on
discrete heritable units (genes)
 Mendel’s experiments suggested that inherited
traits were discrete and constant
http://www.mendelmuseum.org/eng/1online/experim
ent.htm
Why did Mendel succeed in seeing
something that nobody else saw?
1. He counted
2. Chose a good system
3. Chose true-breeding characters
Gregor Mendel
The field of genetics started with a single paper!
Mendel is as important as
Darwin in 19th century science
Mendel did experiments and analyzed the results
mathematically. His research required him to
identify variables, isolate their effects, measure
these variables painstakingly and then subject
the data to mathematical analysis.
He was influenced by his study of physics and
having an interest in meteorology. His
mathematical and statistical approach was also
favored by plant breeders at the time.
Mendel used an Experimental,
Quantitative Approach
Advantages of pea plants for genetic study:
 There are many varieties with distinct heritable
features, or characters (such as color);
character variations are called traits
 Mating of plants can be controlled
 Each pea plant has sperm-producing organs
(stamens) and egg-producing organs (carpels)
 Cross-pollination (fertilization between different
plants) can be achieved by dusting one plant
with pollen from another
1. Self-fertilization
2. Cross-pollination
Mendel Planned Experiments
Carefully
Mendel chose to track only those characters
that varied in an “either-or” manner
He also used varieties that were “truebreeding” (plants that produce offspring of
the same variety when they self-pollinate)
He spent 2 years getting “true” breeding
plants to study
At least three of his traits were available in
seed catalogs of the day
Mendel studied true breeding pea
traits with two distinct forms
Terminology of Breeding
P1 (parental) - pure breeding strain
F1 (filial) – offspring from a parental
cross
They are also referred to as hybrids – because
they are the offspring of two 2 pure-breeding
parents
F2 - produced by self-fertilizing the F1 plants
LE 14-6
3
Phenotype
Genotype
Purple
PP
(homozygous
Purple
Pp
(heterozygous
1
2
1
Purple
Pp
(heterozygous
White
pp
(homozygous
Ratio 3:1
Ratio 1:2:1
1
P Generation
Appearance:
Genetic makeup:
Purple
flowers
PP
White
flowers
pp
P
p
Gametes
F1 Generation
Appearance:
Genetic makeup:
Purple flowers
Pp
1
Gametes:
2
1
P
p
2
F1 sperm
P
p
PP
Pp
Pp
pp
F2 Generation
P
F1 eggs
p
3
:1
The Testcross
How can we tell the genotype of an
individual with the dominant phenotype?
This individual must have one dominant
allele, but could be either homozygous
dominant or heterozygous
The answer is to carry out a testcross:
breeding the mystery individual with a
homozygous recessive individual
If any offspring display the recessive
phenotype, the mystery parent must be
heterozygous
LE 14-7
Dominant phenotype,
unknown genotype:
PP or Pp?
Recessive phenotype,
known genotype:
pp
If Pp,
then 2 offspring purple
and 1 2 offspring white:
If PP,
then all offspring
purple:
p
1
p
P
p
p
Pp
Pp
pp
pp
P
Pp
Pp
P
P
Pp
Pp
Mendel’s Second Law: The Law
of Independent Assortment
Mendel derived the law of segregation by
following a single character
The F1 offspring produced in this cross were
all heterozygous for that one character
A cross between such heterozygotes is
called a monohybrid cross
Mendel identified his second law of
inheritance by following two characters at
the same time
Crossing two, true-breeding parents
differing in two characters produces
dihybrids in the F1 generation, heterozygous
for both characters
A dihybrid cross, a cross between F1
dihybrids, can determine whether two
characters are transmitted to offspring as a
package or independently
LE 14-8
P Generation
YYRR
yyrr
Gametes YR
yr
YyRr
F1 Generation
Hypothesis of
dependent
assortment
Hypothesis of
independent
assortment
Sperm
1
Sperm
1
2
YR
1
2
yr
1
1
2
2
1
4
Yr
1
4
yR
1
4
yr
YR
4
YYRR
YYRr
YyRR
YyRr
YYRr
YYrr
YyRr
Yyrr
YyRR
YyRr
yyRR
yyRr
YyRr
Yyrr
yyRr
yyrr
YR
YYRR
1
YR
Eggs
Eggs
F2 Generation
(predicted
offspring)
4
YyRr
1
Yr
4
yr
YyRr
3
4
yyrr
1
1
yR
4
4
1
Phenotypic ratio 3:1
yr
4
9
16
3
16
3
16
3
16
Phenotypic ratio 9:3:3:1
The law of independent assortment states
that each pair of alleles segregates
independently of other pairs of alleles
during gamete formation
Strictly speaking, this law applies only to
genes on different, nonhomologous
chromosomes
Genes located near each other on the
same chromosome tend to be inherited
together
Probability
Ranges from 0 to 1
Probabilities of all possible events must add up
to 1
Rule of multiplication: The probability that
independent events will occur simultaneously is
the product of their individual probabilities.
Rule of addition: The probability of an event
that can occur in two or more independent
ways is the sum of the different ways.
Multiplication and Addition Rules
Applied to Monohybrid Crosses
The multiplication rule states that the
probability that two or more independent
events will occur together is the product of
their individual probabilities
Probability in an F1 monohybrid cross can
be determined using the multiplication rule
Segregation in a heterozygous plant is like
flipping a coin: Each gamete has a 1/2
chance of carrying the dominant allele and a
1/2 chance of carrying the recessive allele
½ chance of P and ½
chance of p allele
results in ¼ chance of
each homozygous
genotype.
There are two ways to
get the heterozygous
genotype so it is
¼+¼=½
Three genotypes give
the same phenotype.
Solving Complex Genetics Problems
with the Rules of Probability
We can apply the rules of multiplication and
addition to predict the outcome of crosses
involving multiple characters
A dihybrid or other multicharacter cross is
equivalent to two or more independent
monohybrid crosses occurring simultaneously
In calculating the chances for various genotypes,
each character is considered separately, and then
the individual probabilities are multiplied together
YYRR
yyrr
Female Gametes
YyRr
¼
YR
YyRr
¼
Yr
¼
yR
¼
yr
¼ YR
YyRr
Male
gametes
3/16
1/16
YYRr
YyRR
YyRr
YYrR
YYrr
YyRr
Yyrr
YyRR
YyRr
yyRR
yyRr
YyRr
Yyrr
¼ Yr
¼ yR
9/16
3/16
YYRR
¼ yr
yyRr
yyrr
For a dihybrid cross –
the chance that 2 independent events occur
together is the product of their chances of
occurring separately.
 The chance of yellow (YY or Yy) seeds= 3/4 (the dominant
trait)
 The chance of round (RR or Rr) seeds = 3/4 (the dominant
trait)
 The chance of green (yy) seeds= 1/4 (the recessive trait)
 The chance of wrinkled (rr) seeds= 1/4 (the recessive trait)
Therefore:
The chance of yellow and round= 3/4 x 3/4 = 9/16
The chance of yellow and wrinkled= 3/4 x 1/4 = 3/16
The chance of green and round= 1/4 x 3/4 = 3/16
The chance of green and wrinkled= 1/4 x 1/4 = 1/16
Inheritance patterns are often more
complex than predicted by Mendel
The relationship between genotype and
phenotype is rarely as simple as in the pea
plant characters Mendel studied
Many heritable characters are not
determined by only one gene with two
alleles
However, the basic principles of segregation
and independent assortment apply even to
more complex patterns of inheritance
Extending Mendelian Genetics for
a Single Gene
Inheritance of characters by a single gene
may deviate from simple Mendelian patterns
in the following situations:
 When alleles are not completely dominant or
recessive
 When a gene produces multiple phenotypes
 When a gene has more than two alleles
 The forensic characteristics usually have more
than two alleles
The Spectrum of Dominance
Complete dominance occurs when
phenotypes of the heterozygote and
dominant homozygote are identical
In incomplete dominance, the phenotype of
F1 hybrids is somewhere between the
phenotypes of the two parental varieties
In codominance, two dominant alleles affect
the phenotype in separate, distinguishable
ways
Forensic Traits are codominant
P Generation
Red
CRCR
White
CWCW
CR
Gametes
CW
Pink
CRCW
F1 Generation
Gametes
1
1
F2 Generation
2
CR
2
CR
1
2
1
CW
Sperm
2
CW
Eggs
1
1
2
2
CR
CRCR
CRCW
CRCW
CWCW
CW
The Relation Between Dominance
and Phenotype
A dominant allele does not subdue a
recessive allele; alleles don’t interact
Alleles are simply variations in a gene’s
nucleotide sequence
For any gene, dominance/recessiveness
relationships of alleles depend on the level
at which we examine the phenotype
If you look directly at DNA, you can always
detect codominance.
Frequency of Dominant Alleles
Dominant alleles are not always more common in
populations than recessive alleles
For example, one baby out of 400 in the USA is
born with extra fingers or toes
The allele for this trait is dominant to the allele for
the more common trait of five digits per
appendage
In this example, the recessive allele is far more
prevalent than the dominant allele in the
population
Multiple Alleles
Most genes exist in populations in more
than two allelic forms
For example, the four phenotypes of the
ABO blood group in humans are determined
by three alleles for the enzyme (I) that
attaches A or B carbohydrates to red blood
cells: IA, IB, and i.
Polygenic Inheritance
• Quantitative characters are those that vary
in the population along a continuum
• Quantitative variation usually indicates
polygenic inheritance, an additive effect of
two or more genes on a single phenotype
• Skin color in humans is an example of
polygenic inheritance
LE 14-12
AaBbCc
aabbcc
20/64
Fraction of progeny
15/64
6/64
1/64
Aabbcc
AaBbCc
AaBbcc AaBbCc AABbCc AABBCc AABBCC
Nature and Nurture:
The Environmental Impact on Phenotype
Relating Mendel’s Laws to Cells
• Law of Segregation
• Pairs of
characteristics
(alleles) separate
during gamete
formation
• Each cell has two
sets of chromosomes
that are divided to
one set per gamete.
Law of Independent
Assortment
The inheritance of an
allele of one gene
does not influence
the allele inherited at
a second gene.
Genes on different
chromosomes
segregate their
alleles independently.
Offspring acquire genes from
parents by inheriting chromosomes
Children do not inherit particular physical traits
from their parents
It is genes that are actually inherited
Genes are carried on chromosomes.
Mendel identified 7 sets of characters- One per
each of the 7 chromosomes in peas, so his law
worked out perfectly.
Two characters on the same chromosome are
linked together and would have messed up his
law.
Inheritance of Genes
Genes are the units of heredity
Genes are segments of DNA
Each gene has a specific locus on a
certain chromosome
One set of chromosomes is inherited from
each parent
Reproductive cells called gametes
(sperm and eggs) unite, passing genes to
the next generation
Sexual Reproduction
Two parents give rise to offspring that have
unique combinations of genes inherited from
the two parents.
All humans arise from the joining of 1 egg and 1
sperm cell
100% of a person’s DNA is the same within and
throughout a human being’s body.
Whether you look at the cells of a person’s
blood, skin, semen, saliva or hair, the DNA and
genes will be the same.
Chromosomes Come in Sets
• Each human cell (except gametes) has 46
chromosomes arranged in pairs in its nucleus
The two chromosomes in each pair are called
homologous chromosomes
One of each pair came from your mother and
the other came from your father.
Both chromosomes in a pair carry genes
controlling the same inherited characteristics
The sex chromosomes are called X and Y
Human females have a homologous pair
of X chromosomes (XX)
Human males have one X and one Y
chromosome
The 22 pairs of chromosomes that do not
determine sex are called autosomes
Each pair of homologous chromosomes
includes one chromosome from each parent
The 46 chromosomes in a human somatic cell
are two sets of 23: one from the mother and
one from the father
The number of chromosomes in a single set is
represented by n
A cell with two sets is called diploid (2n)
For humans, the diploid number is 46 (2n = 46)
Meiosis reduces of chromosome
number from diploid to haploid
The behavior of chromosomes during
meiosis and fertilization is responsible for
most of the variation that arises in each
generation
Meiosis is preceded by the
replication of chromosomes
Meiosis takes place in two
sets of cell divisions, called
meiosis I and meiosis II
The two cell divisions result
in four daughter cells
Each daughter cell has only
half as many chromosomes
as the parent cell
Key
Maternal set of
chromosomes
Possibility 2
Possibility 1
Paternal set of
chromosomes
Two equally probable
arrangements of
chromosomes at
metaphase I
Metaphase II
Daughter
cells
Combination 1
Combination 2
Combination 3
Combination 4
8 Gamete Combinations
vvvvvvvvvvvvvvvvvvvvvvvvvvvvvvv
Maternal set of
chromosomes (n = 3)
2n = 6
Paternal set of
chromosomes (n = 3)
Two sister chromatids
of one replicated
chromosomes
Centromere
Two nonsister
chromatids in
a homologous pair
Pair of homologous
chromosomes
(one from each set)
LE 13-5
Key
Haploid gametes (n = 23)
Haploid (n)
Ovum (n)
Diploid (2n)
Sperm
cell (n)
MEIOSIS
Ovary
FERTILIZATION
Testis
Diploid
zygote
(2n = 46)
Mitosis and
development
Multicellular diploid
adults (2n = 46)
Homologous pairs of chromosomes orient
randomly at metaphase I of meiosis
In independent assortment, each pair of
chromosomes sorts maternal and paternal
homologues into daughter cells independently of
the other pairs
The number of combinations possible when
chromosomes assort independently into
gametes is 2n, where n is the haploid number
For humans (n = 23), there are more than 8
million (223) possible combinations of
chromosomes
Random Fertilization
Random fertilization adds to genetic
variation because any sperm can fuse with
any ovum (unfertilized egg)
The fusion of gametes produces a zygote
with any of about 64 trillion diploid
combinations
Crossing over adds even more variation
Each zygote has a unique genetic identity
LE 13-11
Nonsister
chromatids
Prophase I
of meiosis
Tetrad
Chiasma,
site of
crossing
over
Metaphase I
Metaphase II
Daughter
cells
Recombinant
chromosomes
Monohybrid Cross: - cross
involving only one character.
Results from Crosses
F1 offspring  the trait expressed was the same as that of one of the
parental lines
 traits did not blend
F2 offspring
 the traits from both parents were expressed in a 3:1
ratio
 while the trait had not been expressed
in the F1, it
remained unchanged as it was passed from the P1 to
the F1 and then to the F2 generation.
CONCLUSION
Traits are inherited as discrete, separate
units.
Mendel’s Conclusions
1. Factors (genes) that determine traits
can be hidden or unexpressed.

Dominant traits have a factor (gene) that is
expressed in the F1 offspring

Recessive traits have a factor (gene) that is
not expressed in the F1 offspring
Mendel’s Conclusions
2. Despite P1 and F1 generations appearing
identical, they must be genetically different.
 Phenotype- observed properties of a trait
 Genotype- the genetic makeup of a trait
 PP1 and F1 seeds have the same phenotype
but different genotypes
Mendel’s Conclusions
3. Since the F1 offspring had factors (genes) for both
smooth and wrinkled - then there must be at least
2 factors for every trait.
•
•
•
Alleles- alternative forms of a gene
Genotype- indicates the combination of alleles
present
Phenotype- indicates the trait observed
These terms differentiate the observed form and
the underlying alleles present at a particular gene.
Mendel’s Model
Mendel developed a hypothesis to
explain the 3:1 inheritance pattern he
observed in F2 offspring
Four related concepts make up this
model
These concepts can be related to what
we now know about genes and
chromosomes
The First Concept
Alternative versions of genes account for
variations in inherited characters
For example, the gene for flower color in
pea plants exists in two versions, one for
purple flowers and the other for white
flowers
These alternative versions of a gene are
now called alleles
Each gene resides at a specific locus on a
specific chromosome
Allele for purple color
Locus for flower color gene
Allele for white color
Homologous
pair of
chromosomes
The Second Concept
For each character, an organism inherits
two alleles, one from each parent
Mendel made this deduction without
knowing about the role of chromosomes
The two alleles at a locus on a chromosome
may be identical, as in the true-breeding
plants of Mendel’s P generation
Alternatively, the two alleles at a locus may
differ, as in the F1 hybrids
The Third Concept
If the two alleles at a locus differ, then
one (the dominant allele) determines the
organism’s appearance, and the other
(the recessive allele) has no noticeable
effect on appearance
In the flower-color example, the F1 plants
had purple flowers because the allele for
that trait is dominant
The Fourth Concept
Known as “the law of segregation”
Two alleles for a heritable character separate
(segregate) during gamete formation and end up
in different gametes
Thus, an egg or a sperm gets only one of the
two alleles that are present in the somatic cells
of an organism
This segregation of alleles corresponds to the
distribution of homologous chromosomes to
different gametes in meiosis
Mendel’s Laws Explain his Data
Mendel’s segregation model accounts for the 3:1
ratio he observed in the F2 generation of his
numerous crosses
The possible combinations of sperm and egg
can be shown using a Punnett square, a
diagram for predicting the results of a genetic
cross between individuals of known genetic
makeup
A capital letter represents a dominant allele, and
a lowercase letter represents a recessive allele
What does the 3:1 ratio of dominant to
recessive traits in the F2 population mean?
It is the basis for Mendel’s Law of
Segregation
Pairs of characteristics separate during
gamete formation.
Review
of
meiosis
Monohybrid Cross: - cross
involving only one character.
Two types of “states”
Homozygous:
 an individual or a locus carries identical
alleles of a given gene.
Heterozygous:
 an individual or a locus carries different
alleles of a given gene
Gametes join randomly to make
new individuals
The Punnett Square
Reginald C. Punnett
Mendel’s Law of Segregation
Members of a gene pairs (alleles) separate
from each other during gamete formation.
The underlying mechanism is separation
and then segregation of homologous
chromosomes during meiosis.
Key terms:
 dominant and recessive traits
 genotype versus phenotype
Mendel’s Law of
Segregation
holds true for
any cross
Molecular Basis of Mendel’s
factors
Mendel’s factors are called alleles.
 versions of the same gene or DNA
sequence.
 differ in DNA sequence at one or more sites.
Genotype and Phenotype
Phenotype
Tall plant
Tall Plant
Genotype
Abbreviation of
Genotype
Homozygous dominant
TT
“tall associated” alleles.
Heterozygous
Short Plant Homozygous dominant
“short associated”
alleles.
Tt
tt
Dihybrid Crosses
Parental lines:
 smooth yellow seed
 wrinkled green seeds
Mendel learned from previous monohybrid
crosses
 smooth was dominant over wrinkled
 yellow was dominant over green
 Pure-breeding smooth yellow genotype
 Pure-breeding green wrinkled genotype
SSYY
ssyy
Dihybrid
Cross
?
Dihybrid cross - F2 generation
315 smooth and yellow
108 smooth and green
101 wrinkled and yellow
32 wrinkled and green
9:3:3:1
parental
new combo
new combo
parental
Fig 3.8
Dihybrid Cross
How does this dihybrid F2 phenotypic ratio of
9:3:3:1 relate to the monohybrid cross
phenotypic ratio of 3:1?
Total smooth
Total wrinkled
315 + 108 = 423
101 +32 = 133
~ 3:1
Total yellow
Total green
315 + 101 = 416
108 + 32 = 140
~ 3:1
Each trait is behaving as expected for a
monohybrid cross.
Inheritance of each trait appears to be independent
of the other trait.
Mendel’s Conclusion
He reasoned that alleles from one gene
pair segregate into gametes
independently of the alleles belonging to
other traits, producing gametes with all
possible combinations of alleles.
Law of Independent Assortment
The inheritance of an allele of one gene
does not influence which allele is
inherited at a second gene.
Two genes on different chromosomes
segregate their alleles independently.
Law of independent assortment
Probability:
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
Independent Events
• 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
Independent events
What is the chance of
an offspring having the
homozygous recessive
genotype when both
parents are doubly
heterozygous?
Independent Events
Dependent Events
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
Dependent Events
Parents are heterozygous for a trait, R.
What is the chance that their child 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
1/2
1/2
R
r
1/2
R
RR
Rr
1/2
r
Rr
rr
So, Rr genotype = (1/2 x 1/2) x 2 = 1/2
RR genotype is (1/2 x 1/2) = ¼
Add these to get the combined probability.
Can use to solve more complicated problems:
AaBBccDdEeFFGghhIiJJKk
x
aaBbCCDdEEffggHhIIjjKk
Crossing Double Heterozygotes
Fig 3.10b
Fig 3.11
Dihybrid Cross
From the 16 possible fertilization
events


- 9 genotypes
- 4 phenotypes
9:3:3:1
Dihybrid cross
Tetrahybrid cross!
Statistical Analysis
Simple cross:
10x as many, but
same ratio
purple x white
F1: all purple
F2: 2850 purple, 1150 white
Use Χ2 test to determine likelihood of getting this result by chance
Χ2 = total of (observed-expected)2/expected over all classes
"Expected" is from null hypothesis - data fit a 3:1 ratio
(2850-3000)2/3000 + (1150-1000)2/1000 = 30!
P is <<less than
5%, so data are
significantly
different from
null hypothesis
Pedigree Analysis
Garrod, 1902 - human traits
followed Mendelian rules
Inborn errors of metabolism
Hint: much more common in first cousin marriages