Probability Calculations in Genetics Problem Solving: Genetics Analysis: An Integrated Approach

Probability Calculations in Genetics
Problem Solving
• A Punnett square can be used to determine the
phenotypes expected in a cross, such as a dihybrid
cross
• The independence of the genes in the cross gives a

quicker way to predict this, by multiplying the
probability of the phenotype at one locus (¾ or ¼) by
the probability of the phenotype at the second locus
(also ¾ or ¼)
• This can be applied to any number of genes in a

cross
1
Genetics Analysis: An Integrated Approach Copyright © 2012 Pearson Education Inc.
The Rediscovery of Mendel’s Work
• Mendel’s work was rediscovered in 1900 by several

botanists working independently
• Each identified the same hereditary principles

described by Mendel
• Mendelian genetics is named for Mendel because

he was the first researcher to explain the observed
hereditary patterns
2
2.4 Probability Theory Predicts Mendelian Ratios
• Mendel recognized that chance is the principle

underlying the segregation of alleles for a given
gene and the independent assortment of alleles of
genes at different loci
• There are four rules of probability theory that

describe and predict the outcome of genetic events
3
The Product Rule
• If two or more events are independent of one

another, the likelihood of their simultaneous or
consecutive occurrence is the product of their
individual probabilities
• This is the product rule, also called the

multiplication rule
4
The Sum Rule
• The sum rule is also called the addition rule
• It defines the joint probability of occurrence of any

two or more equivalent events
• The individual probabilities are summed; this rule is

used when more than one outcome will satisfy the
conditions of the probability question
5
Conditional Probability
• The product and sum rules are used before a cross

is made, in order to predict the likelihood of certain
outcomes
• Conditional probability involves questions asked

after a cross has been made and is applied when
information about the outcome modifies the
probability calculation
6
Example of Conditional Probability
• For cross Gg  Gg, what is the probability that the

yellow-seeded progeny are heterozygous?
• Yellow-seeded offspring make up ¾ of the offspring,

with two possible genotypes: GG and Gg
• As the yellow-seeded offspring cannot be gg, there

is a 2/3 chance they are Gg and a 1/3 chance they
are GG
7
Binomial Probability
• Some questions involve predicting the likelihood

of a series of events (for which there are two
outcomes each time)
• We use binomial probability calculations to

answer this type of question
• It expands the binomial expression to reflect the

number of outcome combinations and the
probability of each
8
Construction of a Binomial Expansion
Formula
• A binomial expansion contains two variables; p, the
frequency of one outcome, and q, the frequency of
the alternative outcome (p and q may or may not be
equal, depending on the type of outcome)
• (p  q)  1, since these are the only two outcomes
• We expand the equation by the power of n, where

n  the number of successive events: (p  q)n
9
Binomial Expansion Formula — Example
• For families with three children, predict the

proportions with each possible combination of boys
and girls
• p  probability of a boy  ½; q  probability of

a girl  ½
• Binomial expansion: (p + q)3  p3  3p2q  3pq2  q3
• p3  1/8 (3 boys); 3p2q  3/8 (2 boys, 1 girl); 3pq2 

3/8 (1 boy, 2 girls); q3  1/8 (3 girls)
10
Application of Binomial Expansion to
Progeny Phenotypes
• In a self-fertilized Gg pea plant, give the proportion of
yellow and green peas in pods with six peas each
• p  probability of yellow peas  3/4; q  probability of

green peas  ¼
• A shortcut to the binomial expansion is Pascal’s

triangle, which is easy to calculate
11
12
13
2.5 Chi-Square Analysis Tests the Fit Between
Observed and Expected Outcomes
• Scientists must be able to make comparisons of

observed and expected results to objectively
determine whether results are consistent with
expectations
• The chi-square test was developed to allow for

these objective comparisons
14
The Normal Distribution
• In large samples outcomes predicted by chance

have a normal (Gaussian) distribution
• This is often described as a “bell-shaped curve”
• The mean (m) is the average outcome, and other

outcomes are distributed around the mean
• The probability of an experimental outcome gets

smaller the further it is from the mean
15
16
The Probability of Particular Outcomes
• Probability of particular outcomes is quantified by a

measurement called standard deviation ()
• In a normal distribution 68.2% of all outcomes fall

within one  of the mean, 95.4% within 2, and
99.8% within 3
• An experimental outcome that is more than 2 from

the mean shows a statistically significant difference
between the observed and expected outcome
17
The Chi-Square Analysis
• The chi-square (2) test is commonly used for

quantifying how closely an experimental observation
matches the expected outcome
• The difference between observed and expected

values are squared, divided by the expected values
and then the values obtained for each outcome are
summed
• 2 = (O  E)2/E; 0 = observed values; E  expected

values
18
Interpreting the Chi-Square Analysis
• The interpretation of the test is done by means of a

probability (P) value
• It is the probability that the results of another

experiment of the same size and structure will
deviate as much or more from the expected results
by chance
• Low 2 values are associated with high P values,

which indicate that chance alone likely explains the
deviations of experimental results from predicted
values
19
Degrees of Freedom
• The P value for an experiment is dependent on the

degrees of freedom (df)
• The df value is equal to the number of outcome

classes, n, minus 1; this is the number of
independent variables
• The chi-square table includes values for different

degrees of freedom and the corresponding P values
20
21
Statistical Significance
• A statistically significant result from 2 analysis is one

for which the P value is less than 0.05
• When any experimental result has less than 5%

probability, the hypothesis of chance is rejected
• P values above 5% indicate a nonsignificant

deviation between observed and expected results
• This results in failure to reject the hypothesis of

chance
22
Chi-Square Analysis of Mendel’s Data
• Modern statistical methods allow us to test

Mendel’s experimental data for compatibility with
his laws
• From statistical analysis of his data, we can

conclude that the results are consistent with the
predictions
23
Monohybrid Cross Example
• For round vs. wrinkled seeds, Mendel observed 5475

round and 1850 wrinkled from his monohybrid cross
(Rr  Rr), for a total of 7324 seeds
• The expected values: (7324)(3/4)  5493 round (R-),

and (7324)(1/4)  1831 wrinkled (rr)
• 2  (5474  5493)2/5493  (1850  1831)2/1831 

0.263
• For df  1, the P value falls between 0.50 and 0.70,

well above the 0.05 cutoff value
24
25
2.6 Autosomal Inheritance and Molecular
Genetics Parallel the Predictions of
Mendel’s Hereditary Predictions
• In the early 1900s biologists began to extend
Mendel’s findings to other organisms
• They also began to identify exceptions to the

hereditary principles
• Mendelian principles can be applied to transmission

of certain traits in humans
26
Autosomal Inheritance
• Autosomal inheritance refers to transmission of

traits carried on autosomes, chromosomes found in
both males and females
• There are two copies of each autosome; so each

individual carries two copies of each autosomal gene
• Individuals with two identical copies are

homozygous; those with two different copies are
heterozygous
27
Pedigrees
• Pedigrees, or family trees, are a way of tracing the

inheritance of traits in humans and some animals
• A standard notation is used to indicate males and

females, their relationships, and the individuals who
show the trait and those who do not
• The generations are indicated by Roman numerals
28
29
Autosomal Dominant Inheritance
• Autosomal dominant inheritance has six

characteristics:
1. Each individual who has the disease has at least

one affected parent
2. Males and females are affected in equal numbers
3. Either sex can transmit the disease allele
30
Autosomal Dominant Inheritance, continued
4. In crosses where one parent is affected and the

other is not, approximately half the offspring
express the disease
5. Two unaffected parents will not have any children

with the disease
6. Two affected parents may produce unaffected

children
31
32
Autosomal Recessive Inheritance
• Autosomal recessive inheritance has six key

features:
1. Individuals who have the disease are often born to

parents who do not
2. If only one parent has the disorder the risk that a

child will have it depends on the genotype of the
other parent
3. If both parents have the disorder, all children will

have it
33
Autosomal Recessive Inheritance,
continued
4. The sex ratio of affected offspring is expected to
be equal
5. The disease is not usually seen in each

generation but if an affected child is produced by
unaffected parents, the risk to subsequent
children is ¼
6. If the disease is rare in the population, unaffected

parents of affected children are likely to be
related to one another
34
35
Molecular Genetics of Mendel’s Traits
• A cornerstone of modern genetics is the integration

of the principles of transmission genetics with those
of molecular genetic analysis
• Transmission of alleles is equated with transmission

of variable DNA sequences that act through mRNA
to produce proteins responsible for phenotypes
36
Molecular Genetics of Mendel’s Traits
• Identification of the genes responsible for the traits

Mendel studied requires demonstration that:
1. Allelic variation coincides with morphologic
variation
2. DNA variation in alleles produces different protein
products
3. Protein products from different alleles have
different structures and functions
4. The functional differences between the protein
variants affect observed morphological variation in
the pea plants
37
Seed Shape (Round and Wrinkled, Gene R)
• R is now called Sbe1; it produces an enzyme that

converts a linear starch molecule (amylose) into a
complex, branched form (amylopectin)
• Plants with one or two wild-type copies have seeds

that contain mostly amylopectin
• Seeds homozygous for the mutant allele contain

mainly amylose, which attracts water that is lost as
the seeds mature, leading to the wrinkled
appearance 38
Stem Length (Tall and Short, Gene Le)
• The Le gene produces giberellin-3-[beta]-

hydroxylase, an enzyme involved in production of the
plant growth hormone, giberellin
• Wild-type plants can produce giberellin and grow tall
• Plants homozygous for the mutant allele lack

giberellin and have a mutant, short, phenotype
39
Seed Color (Green and Yellow Seeds,
Gene Sgr)
• In yellow peas, one or two alleles of the functional
Sgr gene produce an enzyme involved in the
breakdown of chlorophyll so that initially green
seeds lose chlorophyll and turn yellow as they
mature
• A mutation in the production of this enzyme

prevents the chlorophyll breakdown, causing seed
homozygous for this mutation to remain green
40
Flower Color (Purple and White Flowers,
Gene bHLH)
• The product of the bHLH gene is a transcription
factor that activates expression of certain genes
• In this case the genes activated are part of the

pathway that produces the purple pigment
anthocyanin
• Wild-type plants are purple because they are able to

produce the pigment whereas plants homozygous for
mutations in the bHLH gene cannot, and so have
white flowers 41
42
Wild-Type and Mutant Alleles in Mendel’s
Traits
• In all of the traits Mendel studied, the wild-type
alleles are dominant to the recessive mutant alleles
• This is because the mutant alleles are loss-of-

function mutations; if just one functional copy is
present in the plants, the phenotype will be wild-type
• The loss-of-function mutations must be homozygous

in order for the phenotype to be observed
43
Central Conclusions from Molecular Studies
of Mendel’s Traits
1. Inheritance of alleles precisely parallels the pattern
of transmission of morphological variants
2. Morphologic variation results from differences in
structure and function of protein products of the
alleles
3. Molecular analysis led to identification of DNA
sequence differences between alleles, and their
consequences
4. Functional analysis of the protein products of each
allele led to understanding of its function in
producing the phenotype
44

Probability Calculations in Genetics Problem Solving: Genetics Analysis: An Integrated Approach

Încărcat de

Informații document

Titlu original

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

Probability Calculations in Genetics Problem Solving: Genetics Analysis: An Integrated Approach

Încărcat de

Drepturi de autor:

Formate disponibile

Probability Calculations in Genetics

• The independence of the genes in the cross gives a

• This can be applied to any number of genes in a

• Mendel’s work was rediscovered in 1900 by several

• Each identified the same hereditary principles

• Mendelian genetics is named for Mendel because

• Mendel recognized that chance is the principle

• There are four rules of probability theory that

• If two or more events are independent of one

• This is the product rule, also called the

• The sum rule is also called the addition rule

• It defines the joint probability of occurrence of any

• The individual probabilities are summed; this rule is

• The product and sum rules are used before a cross

• Conditional probability involves questions asked

• For cross Gg  Gg, what is the probability that the

• Yellow-seeded offspring make up ¾ of the offspring,

• As the yellow-seeded offspring cannot be gg, there

• Some questions involve predicting the likelihood

• We use binomial probability calculations to

• It expands the binomial expression to reflect the

• (p  q)  1, since these are the only two outcomes

• We expand the equation by the power of n, where

• For families with three children, predict the

• p  probability of a boy  ½; q  probability of

• Binomial expansion: (p + q)3  p3  3p2q  3pq2  q3

• p3  1/8 (3 boys); 3p2q  3/8 (2 boys, 1 girl); 3pq2 

• p  probability of yellow peas  3/4; q  probability of

• A shortcut to the binomial expansion is Pascal’s

• Scientists must be able to make comparisons of

• The chi-square test was developed to allow for

• In large samples outcomes predicted by chance

• This is often described as a “bell-shaped curve”

• The mean (m) is the average outcome, and other

• The probability of an experimental outcome gets

• Probability of particular outcomes is quantified by a

• In a normal distribution 68.2% of all outcomes fall

• An experimental outcome that is more than 2 from

• The chi-square (2) test is commonly used for

• The difference between observed and expected

• 2 = (O  E)2/E; 0 = observed values; E  expected

• The interpretation of the test is done by means of a

• It is the probability that the results of another

• Low 2 values are associated with high P values,

• The P value for an experiment is dependent on the

• The df value is equal to the number of outcome

• The chi-square table includes values for different

• A statistically significant result from 2 analysis is one

• When any experimental result has less than 5%

• P values above 5% indicate a nonsignificant

• This results in failure to reject the hypothesis of

• Modern statistical methods allow us to test

• From statistical analysis of his data, we can

• For round vs. wrinkled seeds, Mendel observed 5475

• The expected values: (7324)(3/4)  5493 round (R-),

• 2  (5474  5493)2/5493  (1850  1831)2/1831 

• For df  1, the P value falls between 0.50 and 0.70,

• They also began to identify exceptions to the

• Mendelian principles can be applied to transmission

• Autosomal inheritance refers to transmission of

• There are two copies of each autosome; so each

• Individuals with two identical copies are

• Pedigrees, or family trees, are a way of tracing the