MODULE 7

GENETIC
INTERACTIONS
RALPH JOYCE CABUG, MD
Objectives of the Lesson:
On completion of the module, the learner should be able to:
1. internalize the importance genetic interactions;
2. know the different processes involved in mutations, epistasis,
polygenic inheritance, pleiotropism, environmental interaction and
extra nuclear inheritance.
3. differentiate mutations, epistasis, polygenic inheritance,
pleiotropism, environmental interaction and extra nuclear inheritance.
●
GENE INTERACTIONS
● Trait can be influenced by more than one gene
● Bateson and Punnett
● Breeding experiments with chickens.
● Different comb shapes
● Wyandottes have “rose” combs,
● Brahmas have “pea” combs
● Leghorns have “single” combs.
● Crosses between Wyandottes and Brahmas
○ “walnut.”
● Comb type is determined by two independently
assorting genes, R and P, each with two
alleles
 GENE INTERACTIONS
● Wyandottes
○ Rose combs
○ RR pp

● Brahmas
○ Pea combs)

○ rr PP.
● F1 hybrids
○ Rr Pp with walnut combs.

● Intercrossed with each other

○ All four types: 9/16 walnut (R- P-),

3/16 rose (R- pp), 3/16 pea (rr P-),

and 1/16 single (rr pp).
GENE INTERACTIONS
 Bateson and Punnett
● 2 independently assorting genes
can affect a trait.
● Different combinations of alleles
from the two genes resulted in
different phenotypes,
● Products at the biochemical or
cellular level.
LESSON EPISTA
01 SIS

6
Learning Outcomes:
1. Describe the process Epistasis
completely.
2. Define the terms such as homozygous
gene, recessive allele, dominant allele, gene
locus, phenotype.
EPISTASIS
 Greek word meaning “stand upon,” referring to the
ability of a mutation at one locus to override a
mutation at another in a double mutant
 Expression of one gene pair masks or modifies the
effect of another gene pair.
 Epistatic- Overriding mutation
 Hypostatic-Overridden mutation
 Antagonistic-masking.
 Complementary/cooperative
EPISTASIS
 Example:
 Homozygous recessive allele

 Prevent or override the expression of

other alleles at a second locus (or

several other loci).
 Epistatic- When an allele has an
overriding effect to the other genes that
are involved;
 Hypostatic
EPISTASIS
1. Distinct phenotypic classes produced
 Discontinuous variation-phenotypic categories
discrete and qualitatively different from one another.
2. Genes considered in each cross
 Different chromosomes

 Assort independently of one another during gamete

formation.

10
 EPISTASIS
3. When we assume that complete dominance exists within a
gene pair, such that AA and Aa or BB and Bb are equivalent
in their genetic effects
 Designations A– or B– for both combinations

 Dash (–) indicates that either allele may be present

without consequence to the phenotype.

11
 EPISTASIS

4. All P1 crosses involve homozygous

individuals (e.g., AABB * aabb, AAbb * aaBB*
aaBB * AAbb2.
 F1 generation consists of only

heterozygotes of genotype AaBb.

12
 EPISTASIS
5. In each example, the F2 generation produced from these
heterozygous parents is our main focus of analysis.
● Two genes are involved
● F2 genotypes fall into four categories: 9/16 A–B–, 3/16 A–bb,
3/16 aaB–, and 1/16 aabb.
● All genotypes in each category are equivalent in their effect on
the phenotype.

13
 Recessive epistasis
 Homozygosity for a recessive allele of one gene hides the effect of
a second gene.
1. Homozygous for the epistatic recessive allele of the first gene,
 Phenotype is independent of the alleles present at the
second (hypostatic) gene.
2. Recessive epistasis reciprocal between the two genes that
determine the trait.

14
 Recessive epistasis
 Homozygosity for a recessive allele of one gene hides the effect of
a second gene.
1. Homozygous for the epistatic recessive allele of the first gene,
 Phenotype is independent of the alleles present at the
second (hypostatic) gene.
2. Recessive epistasis reciprocal between the two genes that
determine the trait.

15
 Recessive epistasis
Yellow Labrador retrievers
 Black, chocolate brown, or yellow
 2 independently assorting coat color genes
 Dominant E allele of the first gene is present
 B allele of the second gene-black
 Recessive bb homozygote-chocolate.
 Double dose of the recessive allele (ee)
 Hides the effect of any combination of
the black or chocolate alleles to yield
yellow.
 Epistatic to any allelic combination at
the second, hypostatic gene, B.
16
 Recessive epistasis
 J

17
● Coat color- 2 pigments synthesized from common
precursor eumelanin and pheomelanin.
● At least copy of the E allele
○ Protein E-make only eumelanin (dark) and
no pheomelanin (light).
● B allele
○ Required for eumelanin synthesis
● b allele
○ Less efficient protein.
● Chocolate E– bb dogs
○ Less eumelanin
● Black dogs
○ At least one B allele (E– B–).
○ More eumelanin
● Yellow dogs
○ Absence of the E protein (in ee dogs)
○ only pheomelanin
18
 RECESSIVE EPISTASIS
Bombay phenotype in humans
 2 parents who appear to have
blood type O
 Should have genotype ii
 Produce child with blood type
A (genotype IAi) or blood type
B (genotype IBi).
 Extremely rare trait, called the
Bombay phenotype
RECESSIVE EPISTASIS
Bombay phenotype in humans
 Arises from homozygosity for a mutant
recessive allele (hh) of a second gene that
masks the effects of any ABO alleles that
might be present.
 Type A
 Make enzyme that adds
polysaccharide A onto a sugar
polymer known as substance H;
 Type B
 Altered form of the enzyme that adds
polysaccharide B onto the sugar
polymer H;
 Type O
 Make neither A-adding nor B-adding
enzyme and thus have an exposed
substance H
 RECESSIVE EPISTASIS
Bombay phenotype
in humans
 All people of A, B, or O phenotype
 At least one dominant wild-type
H allele for the second gene
 Produce some substance H.
 Rare Bombay-phenotype
 Genotype hh for the second
gene
 Do not make substance H at all.
 Individuals appear to be type O.
 hh genotype epistatic to any
combination of IA, IB, and i alleles
(except for ii.).
 RECESSIVE EPISTASIS
White sweet pea flowers
 William Bateson
 Cross between 2 lines of
pure-breeding white-flowered sweet
peas
 All of the F1 progeny were Purple
 Self-pollination- 9 purple: 7
white in the F2 generation.
 2 genes work in tandem to
produce purple sweet pea
flowers, and a dominant allele of
each gene must be present to
produce that color.
 RECESSIVE EPISTASIS
White sweet pea flowers
 2 enzymes needed to catalyze sequential
biochemical reactions to change a
colorless precursor into a purple pigment,
 A_B_ genotypic class
 Produces active forms of both
required enzymes
 Other three genotypic classes (A– bb, aa
B–, and aa bb)
 Do not specify functional forms of one
or the other requisite enzyme
 No color/white
RECESSIVE EPISTASIS
White sweet pea flowers
 9:7 ratio vs 9:3:3:1 ratio.

 Phenotypic signature of
reciprocal recessive epistasis
 aa is epistatic to B, and bb is

epistatic to A.
 aa or bb-flowers will be white

even with dominant allele

Dominant epistasis
 Epistasis can also be caused by a
dominant allele.
 Depending on details of the biochemical
pathway involved
 Can result in either of 2 different
phenotypic ratios.
 Dominant epistasis
Squash fruit color
 2 genes influence the color of the fruit
 One gene
 Dominant allele (A_) determines
yellow
 Homozygotes for the recessive
allele (aa) are green.
 Second gene
 Dominant allele (B_) produces
white,
 bb fruit may be either yellow or
green
 Depending on the genotype of
the first gene.
 Dominant epistasis
Squash fruit color
 Interaction between these two genes
 B
 Hides the effects of either A– or aa,
 Produce white fruit
 Epistatic to any genotype of the A
gene.
 Recessive b allele
 No effect on fruit color determined by
gene A.
 Cross between white F1 dihybrids (Aa Bb)
 F2 phenotypic ratio is 12 white : 3
yellow : 1 green (Fig. 3.17a).
 The 12 includes two genotypic classes:
9 A– B– and 3 aa B–.
Dominant epistasis
EPISTASIS
Chicken feather color
 Variant ratio
 White leghorns
 Doubly dominant AA BB genotype for
feather color
 White wyandottes
 Homozygous recessive for both genes
(aa bb).
 Cross between these two pure-breeding white
strains
 F1 generation,
 All-white dihybrid (Aa Bb)
 F2
 Ratio of white to colorful is 13:3
 EPISTASIS
Chicken feather color
 Dominant epistasis
 B is epistatic to A
 A allele-produce color only in
absence of B
 a, B, and b alleles-produce
no color.
 13:3 ratio
 9 A– B–, 3 aa B–, and 1 aa
bb
 Produce only white.
EPISTASIS
 EPISTASIS
 Important points
 Interaction between alleles of different genes, not between alleles of the same
gene.
 Dihybrid crosses:
 F2 phenotypic ratios depend on the functions of the specific alleles and
the particular biochemical pathways
 Labrador retriever and Sweet pea
 Recessive alleles nonfunctional or specify weakly functional protein.
 Phenotypic ratios differ with biochemical pathways
 EPISTASIS
 Important points
 Recessive epistasis
 Dominant alleles of the two genes function in the same pathway to
achieve a common outcome.
 Labrador retriever: B and E both function to generate black
hairs.
 Dominant epistasis
 Dominant alleles of the two genes have antagonistic functions.
 Squash and chicken color: Dominant allele of gene B prevents
deposition of a pigment whose synthesis depends on the dominant
allele of gene A.
EPISTASIS
 Genes in the same cellular pathway.
 Simple biochemical pathway
 Epistatic mutation-gene earlier in the

pathway
 Mutant phenotype of the upstream

gene takes precedence

EPISTASIS
 Difficult to screen
 Combining candidate mutations pairwise to form
double mutants.
 How is the double mutant identified?
 Tetrad analysis

 Example: Ascus
EPISTASIS
 Example: Ascus
 Consider the cross:
END

37
 Thanks!
Do you have any questions?

CREDITS: This presentation template was created by Slidesgo, and

includes icons by Flaticon, and infographics & images by Freepik
Please keep this slide for attribution
References

Principles of Genetics by Snustad

Introduction to Genetic Analysis by Griffiths
Genetics: From genes to genomes by Hartwell

39
 Lesson 2
POLYGENIC
INHERITANCE
RALPH JOYCE CABUG, MD
LEARNING OUTCOMES
1. Determine the effects of Polygenic inheritance.
2. Differentiate Polygenic inheritance from Mendelian
inheritance patterns.
3. Explain the environmental effects on human
phenotypes and phenotypes of other
organisms.
 Polygenic inheritance
● Describes the inheritance of traits that are determined by more than one gene.
● Polygenes
● Produce specific traits when they are expressed together.
● Differs from Mendelian inheritance patterns
● Many possible phenotypes (physical characteristics) that are determined by
interactions among several alleles.
● Examples:
○ Skin color, eye color, hair color, body shape, height, and weight.
 Polygenic inheritance
● Height, eye color, and hair color
○ Slightly different forms
○ Controlled by many genes
○ Example:
■ 2 major eye color genes
■ At least 14 other genes that play roles in determining a person’s
exact eye color.
 Polygenic inheritance

● Height, eye color, and hair color

○ Slightly different forms
○ Controlled by many genes
○ Example:
■ 2 major eye color genes
■ At least 14 other genes that play roles in determining
a person’s exact eye color.
Wheat kernels
● 3 genes that make reddish pigment:
○ A, B, and C.
○ With two alleles
■ Capital-letter allele
● Makes pigment
■ Lowercase allele
● does not
■ Additive effects
■ aa-no pigment
■ Aa-some amount of pigment
■ AA-contribute more pigment
■ Same for the B and C genes.
Variable expressivity vs incomplete
penetrance
 Retinoblastoma
 Arises from a dominant mutation in one gene
 About 75% of people who carry the mutant allele develop
the disease.
 Penetrance
 Proportion of individuals with a particular genotype who
show the expected phenotype.
 Mendel traits-Complete (100%)
 Incomplete-Retinoblastoma. (75%)
 Incomplete penetrance

● Incomplete penetrance
○ Individuals with a certain genotype may or
may not develop a phenotype associated with
the genotype.
○ Ex: Same disease- causing genotype for a
hereditary disorder, some might never actually
develop the disorder.
Incomplete penetrance
 Incomplete penetrance

● Complete penetrance
○ All six squares are dark green.
● Incomplete penetrance
○ Three of the squares are dark green, and three of the
squares are white.
● Squares-represent individuals of the same genotype for the
gene of interest.
Variable expressivity vs incomplete
penetrance
 Same genotype - different phenotypes.
 Example:
 Genetic disorder
 Same disease genotype-stronger or weaker forms or no disorder at all.
 Expressivity
 Refers to the degree or intensity with which a particular genotype is expressed in
a phenotype.
 Variable
 Retinoblastoma (one or both eyes affected)
 Unvarying
 Pea color (all yy peas are green).
Variable expressivity vs incomplete
penetrance
 Variable expressivity
 Phenotype may be stronger or weaker in different people with the
same genotype.
 Ex: Disease-causing genotype
 Some-severe form
 Others-milder form.
Variable expressivity vs incomplete penetrance
Variable expressivity vs incomplete
penetrance
 Narrow Expressivity vs Variable expressivity
What causes variable expressivity
and incomplete penetrance?
● Other genes and environmental effects
● Ex: Disease-causing alleles of one
gene may be suppressed by alleles of
another gene elsewhere in the genome
● Overall health may influence the
strength of a disease phenotype.
Modifier genes
● Major genes have a large influence
● Modifier genes have a more subtle, secondary effect.
○ Alter the phenotypes produced by the alleles of other
genes.
○ No formal distinction
○ Continuum
● Genetic background.
○ Set of unknown modifier genes that influence the
action of known genes
 Modifier genes
Example:
● Length of a mouse’s tail.
○ Mutant T allele
■ Shortening of the normally long wild-type tail.
■ Not all mice carrying the T mutation have the same
length tail.
● One inbred line-75% as long as normal tails
● Another inbred line-50% normal length
● Third line-10% as long as wild-type tails.
Environmental effects
 Phenotypes vary because they are affected by the
environment.
 Weight

 Genetic tendency to be underweight or obese

 Depend on diet and exercise

 Greater role

 Hair color

 May depend on your genes—until you dye your hair

purple!
Environmental effects
Phenylketonuria (PKU)
 Homozygous for disease alleles of the PKU

gene
 Lack activity of an enzyme that breaks
down the amino acid phenylalanine.
 Phenylalanine rapidly builds up to toxic
levels in their bodies.
Environmental effects
Phenylketonuria (PKU)
 Not treated-Stop brain from developing normally
 Intellectual disability, seizures, and mood disorders.
 Diet low in phenylalanine.
 Few, or even no, symptoms
 Newborn Screening
Environmental effects
Examples
 Temperature
 Unique coat color pattern of Siamese cats
 Homozygous for one of the multiple alleles
of a gene that encodes an enzyme
catalyzing the production of the dark
pigment melanin.
 Temperature sensitive.
 Not function at the cat’s normal core
body temperature.
 Active
 Lower temperatures in extremities
 Production of melanin

 What is the permissive condition?

What is the restrictive condition?
Environmental effects
 Temperature

 Survivability.
 Experimentally bred fruit fly (Drosophila melanogaster)

 Develop and multiply normally at temperatures between

18°C and 29°C;

 Beyond that cutoff for a short time-Reversibly paralyzed;

 Few hours-die.

 Temperature-sensitive allele of the shibire gene

 Protein essential for nerve cell transmission.

 Conditional lethal
Environmental effects
 Genetically normal individuals
 Phenocopy
 Change in phenotype due to exposure
to chemicals or other environmental
agents that produce phenotypic
consequences similar to mutant alleles
 Not heritable
 Ex:
 Early 1960s
 Ingestion of sedative thalidomide by pregnant women produced a
phenocopy of a rare dominant trait called phocomelia.
 Disrupt limb development
 Mimicked effect of phocomelia-causing mutation.
Environmental effects
 Cardiovascular disease and lung cancer
 People may inherit a propensity to heart disease

 Environmental factors of diet and exercise

contribute to the occurrence (penetrance) and
seriousness (expressivity)
 Genetically prone to lung cancer

 But penetrance strongly determined by whether they

choose to smoke.
Environmental effects
 Mendel’s inbred populations
 Alleles of all but one of thesegenes were invariant
 Discontinuous trait (or discrete trait).
 Clear cut phenotypes that result from alternative alleles

 Either short or tall, and pea plant height

 Continuous phenotypic variation

 Determined by alleles of many different genes whose

interaction with each other and the environment produce the

trait
 Quantitative trait

 Human populations are not inbred

 Height

 Range of values
Thank you!
Do you have any questions?
Credits.
Genetics Genes to Genome by Hartwell
Principles of Genetics by Snustad
MODULE 7
LESSON 3
PLEIOTROPISM
RALPH JOYCE CABUG, MD
 2

Learning Outcomes:
1. Explain the phenomenon of pleiotropy.
2. Identify examples of conditions
manifesting pleiotropy
 3

Pleiotropy
 Mutation-genetic alteration that causes a change in
phenotype or expression of that gene.
 Genetic changes and phenotype changes
 Pleiotropy
 Gene controlling multiple traits.
 One gene control multiple phenotypic traits in the
organism.
 Many different forms
 Cause inherited diseases and disorders.
 Mutation-> Affects all of the phenotype traits that the
gene was controlling.
 4

Pleiotropy
 Antagonistic pleiotropy
 Some of the traits that are expressed

end up being beneficial to the

organism but the others end up being
detrimental.
 5

Pleiotropy
 Marfan syndrome
 Autosomal dominant
mutation
 Connective tissue protein
fibrillin.
 Multiple effects
 Lens dislocation,
increased risk of aortic
aneurysm, and
lengthened long bones in
limbs.
 Abraham Lincoln
 6

Pleiotropy
● Porphyria variegata.
○ Autosomal dominant disorder
○ Afflicted individuals cannot adequately
metabolize the porphyrin component of
hemoglobin
○ Accumulation-hematuria
○ Abdominal pain, muscular weakness,
fever, a racing pulse, insomnia,
headaches, vision problems (that can
lead to blindness), delirium, and
ultimately convulsions.
○ George III, King of England during the
American Revolution
 7

Table of Contents.
Albinism
 Mutation of the TYR gene,
also termed tyrosinase.
 Most common form of
albinism.
 Alters production of
melanin
 Absence of color in an
organism's eyes, hair, and
skin
 Rapid-eye movement,
light sensitivity, and
strabismus.
 Pleiotropy
Oculocutaneous albinism
● Dental manifestations:
● Severe halitosis,1 gingivitis, gingival bleeding, ulcerations of oral mucosa
(such as Sutton’s recurrent aphthous ulcers on the tongue and hard
palate),1 and chronic periodontal diseases.
● Extreme dry lips1 and angular cheilitis.
● Microstomia and limited opening
● Highly susceptible to sun exposure and skin damage.
○ Skin erythema, blistering and cutaneous cancers, such as melanoma. 1
○ Head and neck oral cancer examination,
 Pleiotropy
Oculocutaneous albinism
 Oculocutaneous albinism
● Hermansky-Pudlak
○ Genetic platelet deficiency found primarily in Puerto Rican
albinism populations
○ Bleeding time test
○ Bruising, frequent nose bleeds, and report excessive
bleeding after surgery or tissue trauma after dental work.
○ Referral to a hematologist for hematologic and genetic
testing may be prudent.2,4,5
 Pleiotropy
Autism and schizophrenia
 Pleiotropy in genes has been linked between certain psychiatric disorders
 Deletion in the 22q11.2 region of chromosome 22 has been associated with schizophrenia
and autism.
 Different clinical manifestations-Depends on the stage of life at which the individual
develops the disorder.
 Childhood manifestation:
 Autism
 Schizophrenia or other psychotic disorders
 Adolescent and later expression of the gene deletion
 Pleiotropy
Autism and schizophrenia
 No increased risk found for adult schizophrenia in patients who experienced autism in
childhood.
 2013 study
 Genetically linked five psychiatric disorders, including schizophrenia and autism.
 Single nucleotide polymorphism of two genes involved in calcium channel signaling
with neurons.
 CACNA1C-influence cognition.
 Autism
 Schizophrenia and bipolar disorder.
 Clustering within patients themselves or families.
 Heritability of schizophrenia is 70% to 90%,
 Pleiotropy
Phenylketonuria (PKU)
 Mental retardation and reduced hair and skin
pigmentation
 Large number of mutations in the single gene on
chromosome 12 that codes forthe enzyme
phenylalanine hydroxylase, which converts the
amino acid phenylalanine to tyrosine.
 Unconverted phenylalanine builds up
 Toxic to the developing nervous system of newborn
and infant children.
 Classic PKU-most dangerous; common in infants
 Pleiotropy
Phenylketonuria (PKU)
 Fair hair and skin.
 US: 1 in 10,000 births.
 Newborn screening
 Mutation in the PAH gene
 Manage one's diet.
 Foods with high levels of protein must be avoided.
 Special PKU formula
 Oral health implications
 14

Pleiotropy
 Mini-muscle" allele
 Gene recently discovered in laboratory house mice,
termed "mini-muscle“
 Mutation-> 50% reduction in hindlimb muscle mass
as its primary effect
 Smaller hindlimb muscle mass
 Lower heart rates during physical activity
 Higher endurance.
 Exhibit larger kidneys and livers.
 Higher per-gram aerobic capacity.
 Mendelian recessive behavior.
 Single nucleotide polymorphism (SNP)
 Intron of the myosin heavy polypeptide 4 gene
 15

Pleiotropy
 Frizzle feather trait
 Feathers all curl outward and upward
rather than lying flat against the body.
 Deletion in the genomic region coding for
α-Keratin.
 Increased metabolism, higher food
consumption, accelerated heart rate, and
delayed sexual maturity
 16

Pleiotropy
 Domesticated chicken
 Rapid selection
 Unrelated phenotypes having high
correlations, suggesting pleiotropic, or
at least close linkage, effects
 Comb mass and physiological
structures related to reproductive
abilities.
 17

Pleiotropy
 Domesticated chicken
 Both males and females with larger combs
have higher bone density and strength
 Females deposit more calcium into
eggshells.
 HAO1 and BMP2
 affect medullary bone
 Located at the same locus as the
gene affecting comb mass.
 Higher levels-more eggs and display
less egg incubation behavior.
 18

Thank you!

Do you have any questions?

 19

Credits.
 https://decisionsindentistry.com/article/o
ral-health-implications-of-a-patient-with-
albinism-and-bilateral-maxillary-
paramolars/#:~:text=and%20educational%
20pamphlets.-
,ORAL%20MANIFESTATIONS,1%20and%20ch
ronic%20periodontal%20diseases.
 Principles of genetics by Snustad
 Genetics from genes to genome by
Hartwell
 MODULE 7
Lesson 4
GENETIC INTERACTION
slidesmania.com

RALPH JOYCE C. CABUG, MD

1
 Learning Outcomes:
1. Define gene interaction.
2. Predict the outcome of crosses involving epistasis,
complementation, gene modifiers, and gene redundancy.
3. Describe examples that explain the molecular mechanisms
of epistasis, complementation, gene modifier effects, and
gene redundancy.
slidesmania.com

2
 3
slidesmania.com
 4
slidesmania.com
 Epistasis
 Early 1900s:
 William Bateson and Reginald Punnett
 Study crosses involving the sweet pea, Lathyrus odoratus.
 Wild sweet pea has purple flowers.
 True breeding mutant varieties with white flowers.
 Cross true-breeding purple-flowered plant to a true-breeding white-flowered
plant
 F1 generation had all purple-flowered plants
 F2 generation (produced by self-fertilization of the F1 generation)
slidesmania.com

 Purple- and white flowered plants in a 3:1 ratio.

5
 Epistasis
 Bateson and Punnett
 2 different varieties of white-flowered plants.
 F1 generation plants had purple flowers
 F2 generation: 9 purple to 7 white.
 2 different genes were involved, with the
following relationship:
 C (one purple-color-producing) allele is
dominant to c (white).
 P (another purple-color-producing) allele is
dominant to p (white).
 cc masks the P producing white color
slidesmania.com

 pp masks the C allele producing white color.

6
 Epistasis
 When the alleles of one gene mask the phenotypic effects of the
alleles of another gene
 Describe epistasis relative to a particular phenotype.
 Wild-type phenotype as their reference phenotype
slidesmania.com

7
 Epistasis
 Sweet peas:
 Purple flowers are wild type.
 Homozygosity for the white allele of one gene masks the
expression of the purple-producing allele of another gene.
 cc genotype is epistatic to a purple phenotype
 pp genotype is also epistatic to a purple phenotype.

 cc is epistatic to PP or Pp
 pp is epistatic to CC or Cc.

 Recessive epistasis.
slidesmania.com

 Purple or white flowers—in a 9:7 ratio.

8
 9
Epistasis
slidesmania.com
 Epistasis
 Complementation
 Production of offspring with a wild-type
phenotype from parents that both display the
same or similar recessive phenotype.
 Purple-flowered F1 offspring obtained from
two white-flowered parents.
 Offspring must have one wild-type allele of
both genes to display the wild-type
slidesmania.com

phenotype.

10
 Why is complementation an important experimental
observation?

When geneticists observe complementation in a genetic cross,

this result suggests that the recessive phenotype in the two parent
strains is caused by mutant alleles in two different genes.
slidesmania.com

11
 A Gene Interaction Can Result in a Gene Modifier Effect

 Coat color in rodents

 Produces three phenotypes.
 One gene
 A (for Agouti)
 Other gene
 C (for color production) and c.
 Cross heterozygous for both genes
 Agouti, black, and albino offspring
slidesmania.com

in a 9:3:4 ratio.

12
 Gene Redundancy
 Studying model organisms such as Escherichia coli (a bacterium),
Saccharomyces cerevisiae (baker’s yeast), Arabidopsis thaliana (a model
plant), Drosophila melanogaster (fruit fly), Caenorhabditis elegans (a
nematode worm), and Mus musculus (the laboratory mouse).
 Isolation of mutant alleles that alter the phenotypes of these organisms->
New kinds of gene interactions.
 Intentionally producing loss-of-function alleles in a gene of interest.
 Common approach for investigating gene function
 Create an organism that is homozygous for a loss-of-function allele
slidesmania.com

 Gene knockout.

13
 Gene Redundancy
Gene knockouts
 How the gene affects the structure and function of cells or the phenotypes
of organisms.
 Example:
 Knocked out gene in a mouse-> unable to hear
 Role of the functional gene is to promote the formation of ear
structures that are vital for hearing.
 Studying many gene knockouts
 Discovered that many knockouts have no obvious effect on phenotype
slidesmania.com

at the cellular level or the level of discernible traits.

14
 Gene Redundancy
Gene knockouts
 Maketwo or more gene knockouts in the same organism.
 Some produce a phenotypic change even though the single knockouts have no effect
 Gene redundancy
 Only one dominant allele of either of two genes is necessary to produce
phenotype
 Phenomenon in which in which one gene can compensate for the loss of function
of another gene.
 Due to different underlying causes.
slidesmania.com

 One common reason: Gene duplication.

15
 Gene Redundancy
Gene knockouts
 Paralogs
 Not identical copies due to the
accumulation of random changes
during evolution
 1 gene missing-> Paralog may be
able to carry out the missing
function.
 Example:
 Genes A and B could be
slidesmania.com

paralogs of each other.

16
 Gene Redundancy
Gene knockouts
 Gene redundancy
 Proteins involved in a common cellular function.
 1 protein missing due to a gene knockout
 Function of another protein may be increased-
>Compensate for the missing protein-> Overcome
slidesmania.com

the defect.

17
 Gene Redundancy
 George Shull
 One of the first studies that illustrated the
phenomenon of gene redundancy.
 Shepherd’s purse-weed; member of the mustard
family.
 Shape of the seed capsule- commonly triangular
 Strains producing smaller ovate capsules
 Loss- of-function alleles in two different
genes (ttvv).
slidesmania.com

 Double gene knockout.

18
 Gene Redundancy
 George Shull
 Crossed a true-breeding plant with triangular
capsules to a plant having ovate capsules
 F1 generation all had triangular capsules.
 F2 generation: 15:1 ratio of plants having
triangular capsules to ovate capsules.
 Gene redundancy
 At least one functional copy of either
gene (T or V) is sufficient to produce
slidesmania.com

the triangular phenotype.

 T and V are functional alleles of
redundant genes.
19
 Gene Redundancy
Maize
 2 genes, A and B, control leaf development.
 Normal broad leaves
 Dominant A allele or a dominant B allele (A−
B−, A− bb, or aa B–).
 Skinny
 Neither dominant allele (aa bb)
 Contain too few cells
slidesmania.com

20
 Gene Redundancy
Maize
 F2 phenotypic ratio signifying
redundant gene action is 15:1.
 Proteins (A and B)
 Encoded by the dominant
alleles
 Parallel, redundant pathways
that recruit precursor cells to
slidesmania.com

become part of the leaf

21
 Gene Redundancy
Maize
slidesmania.com

22
 thank you!
Do you have any questions?
hello@mail.com
555-111-222
mydomain.com
slidesmania.com

23
 Free themes and templates for
Google Slides or PowerPoint

Sharing is caring!
NOT to be sold as is or modified!
slidesmania.com

Read FAQ on slidesmania.com

Do not remove the slidesmania.com text on the sides.
24
 Lesson 5
ENVIRONMENTAL
EFFECTS ON GENE
EXPRESSION
SLIDESMANIA.COM

RALPH JOYCE CABUG, MD

 Learning Outcomes:

01 Describe the environmental

effects on gene expression.
02 Determine the effects of
temperature on gene
expression.

03
Identify the main factors that
determine an organism’s traits
SLIDESMANIA.COM
SLIDESMANIA.COM
SLIDESMANIA.COM
SLIDESMANIA.COM
 Environmental Effects
 Range of conditions, rather than
simply observing phenotypes under
two different conditions.
 Norm of reaction
 Refers to the effects of
environmental variation on a
phenotype.
 Phenotypic range seen in
individuals with a particular
genotype.
SLIDESMANIA.COM
 Norm of Reaction

 True-breeding strains with same

genotypes
 Subject them to different
environmental conditions.
 Facet number in the eyes of fruit flies,
Drosophila melanogaster.
 Compound eyes composed of many
individual facets.
SLIDESMANIA.COM
 Norm of Reaction

 Norm of reaction for facet

number in genetically identical
fruit flies at different
temperatures.
 Lower temperature (15°C)
 Facet number is over
1000
 Higher temperature (30°C),
 it is approximately 750.
SLIDESMANIA.COM
 Environmental
Agents (Teratogens)
 An agent that can
cause a birth defect by
interfering with normal
embryonic or fetal
development
 Drugs and chemicals
SLIDESMANIA.COM
 Environmental
Agents (Teratogens)
Drugs and chemicals
Thalidomide Tragedy
 1958 to 1962
 Sedative during the first trimester
 Between 20 and 35 days postconception
 Severe limb anomalies in babies
 Phocomelia
 Limb that is malformed due to absence of some or all of the long bones,
SLIDESMANIA.COM

with retention of digits giving a ‘flipper’ or ‘seallike’ appearance.

 Environmental
Agents (Teratogens)
Drugs and chemicals
Thalidomide Tragedy
 Ear defects, microphthalmia and cleft lip/palate.
 40% died in early infancy
 Thalidomiders have grown up and had children of their own, and in
some cases these offspring have also had similar defects.
SLIDESMANIA.COM
 Environmental
Agents (Teratogens)
Fetal Alcohol Syndrome
 Large quantities of

alcohol
during pregnancy
 Small head circumference

 Distinctive facial appearance

with short palpebral fissures, a smooth philtrum and a

SLIDESMANIA.COM

thin upper lip.

 Environmental
Agents (Teratogens)
Fetal Alcohol Syndrome
 Ear helix-‘railroad’

configuration of the folds

 Hands -‘hockey-stick’ crease

 Developmental delay with hyperactivity and a reduced sense

of moral responsibility
 ‘fetal alcohol spectrum disorder’

 ‘alcohol-related neurodevelopmental defects’

SLIDESMANIA.COM

 Total abstinence is advised throughout pregnancy.

 Environmental
Agents (Teratogens)
Infectious agents
 Interfere with embryogenesis
and fetal development
 Developing brain, eyes, and
ears are particularly susceptible
to damage by infection.
SLIDESMANIA.COM
 Environmental Agents (Teratogens)

 Physical Agents
 Two specific physical agents can have

teratogenic effects:
 Ionizing radiation and prolonged
hyperthermia
SLIDESMANIA.COM
 Environmental Agents (Teratogens)

 Physical Agents
1. Ionizing Radiation
 Heavy doses in excess of those used in routine diagnostic
radiography
 Microcephaly and ocular defects
 2 to 5 weeks post-conception.
 Mutagenic and carcinogenic effects
 Radiography should be avoided during pregnancy if
possible.
SLIDESMANIA.COM
 Environmental Agents (Teratogens)

 Physical Agents
2. Prolonged Hyperthermia
 Early pregnancy

 Microcephaly and microphthalmia

 Neuronal migration defects.

 Avoid excessive use of hot baths and saunas

during the first trimester.

SLIDESMANIA.COM
  Periodontitis is inflammatory condition and genetic
factors play a role in its etiology.
 Genetic factors play a role in the predisposition and

progression of periodontal diseases.

 Periodontal diseases occur due to complex interplay

between Environmental factors, Genetic factors, Life

style factors, Systemic diseases and other factors.
SLIDESMANIA.COM
SLIDESMANIA.COM
 Environmental Influences

 Genetic risk factors like gene–gene interactions, gene-

environmental, and environment–gene-life style interaction
need to be present simultaneously for the phenotype to
develop in periodontal disease.
 The study of the role of genetic factors in determining
health and disease in families and in populations, and the
interplay of such genetic factors with environmental factors
is known as Genetic Epidemiology.
SLIDESMANIA.COM
 Genetic Basis of Periodontitis

 Periodontitis is a complex chronic inflammatory disease

which affects gingiva, periodontal ligament, cementum,
and alveolar bone.
 Periodontitis is classified into Chronic Periodontitis (CP) and
Aggressive Periodontitis(AgP).
 AgP occurs most often at a younger age (upto 35 years old)
and these cases involve more genetic risk factors than CP
cases
SLIDESMANIA.COM
 Genetic contribution to the aetiology of periodontitis

Genetic Basis of Periodontitis

SLIDESMANIA.COM
 Genetic Basis of Periodontitis

 The evidence for a genetic predisposition to aggressive

periodontitis comes from segregation analyses of families
with affected individuals in two or more generations.
 It inherited in a Mendelian manner, and both autosomal
modes and X-linked transmission have been proposed.
SLIDESMANIA.COM
 Genetic Basis of Periodontitis

 GENES ASSOCIATED WITH AGGRESSIVE PERIODONTITIS

 IL-1 cluster, IL-4,6,10,12,13,18
 TNF-a
 TGF-b
 Vit. D receptor
 Estrogen receptor
 RANK/RANKL/OPG,
 MMP 1,2,3,9,
 TIMP
SLIDESMANIA.COM

 HLA
 CD14
 Chronic Periodontitis in
Relation to Genetics
o In contrast to aggressive periodontitis,
chronic periodontitis does not typically
follow a simple pattern of familial
transmission or distribution.
o The twin study is most popular method
that supports the genetic aspects of
chronic periodontitis.
Corey et al. (1993)
revealed that approximately half of the variance in
SLIDESMANIA.COM

disease in the population is attributed to genetic

variance. 25
 Michalowicz et al. (1991)
•The rate of occurrence of periodontitis was more in
monozygotic twins (23%) as compared to Dizygotic twins
( 8%).
•These studies are independent of environmental factors
showing that gene control only the biologic mode of
inheritance and not the behavioral.

GENES ASSOCIATED WITH CHRONIC PERIODONTITIS

• Interleukin-1, 2, 4, 6, 10
• Fcg receptor
• TNF
SLIDESMANIA.COM

• Vitamin D receptor
26
 Evidence for the Role of Genetic
Variants in Periodontitis

Familial Aggregation:
German studies of familial nature in the early 20th century have shown
aggregation of chronic forms of periodontitis in families. This
strongly suggested genetic predisposition.
SLIDESMANIA.COM

27
 Twin study
oMichalowicz et al. (1991) studied dizygous twins reared
together and apart and monozygous twins reared together
and apart.
oMean probing depth and attachment level varied less for
monozygous twins than dizygous twins.
oTwin groups had similar oral hygiene and smoking history.
oConcluded genetics plays a role in susceptibility to
periodontal disease.
SLIDESMANIA.COM

28
 Segregation analysis
• Marazita et al. (1994) studied >100 families,
segregating aggressive forms of periodontitis, and
found support for autosomal dominant transmission.
Concluded autosomal dominant inheritance with ~70%
penetrance occurred in Blacks and non-Blacks.

• While others Beaty et al. (1987), Long et al. (1987),

Saxen et al. (1980) have found support for autosomal
recessive transmission of aggressive periodontitis.
SLIDESMANIA.COM

29
 Linkage analysis
1. Boughman et al. (1986) gene for Dentinogenesis imperfecta-III had been
previously localized to chromosome 4. They showed close linkage of gene
for Aggressive periodontitis( AgP) to this DGI-III gene.
2. Hart et al. (1993) evaluated support for linkage of AgP near chromosome
4 in different population of families. Results showed that in these
populations no linkage existed.

3. Li and co-workers (2004) reported evidence of a gene responsible for

localized aggressive periodontitis located on chromosome 1q25.
SLIDESMANIA.COM

30
 Genetic Syndromes Associated
With Periodontitis
SLIDESMANIA.COM

31
 PAPILLON-LEFEVRE SYNDROME
o Autosomal recessive disorder
o Characterized by Cutaneous
and Oral manifestations.
o Skin lesions consist of
keratotic lesions of palmar
and planter surfaces.
SLIDESMANIA.COM

32
 oOral lesions are characterized by Aggressive periodontitis leading
to severe destruction of alveolar bone, which leads to mobility,
pathological migration and loss of teeth.
oGene responsible: Cathepsin C, Lysosomal protease.
SLIDESMANIA.COM

33
 EHLER DANLOS SYNDROME

o Genetic defect in collagen and connective tissue

synthesis and structure.
o Characterized by joint hypermobility, cutaneous
fragility and hyperextensibility.
SLIDESMANIA.COM

34
 35
SLIDESMANIA.COM
 36
SLIDESMANIA.COM
 37
SLIDESMANIA.COM
 oHyperelasticity of joints along
with defect in collagen causing
more periodontal destruction.
oEDS can be associated with
Ligneous periodontitis (gen.
membranous gingival enlargement
due to accumulation of fibrin
deposits associated with severe
bone loss).
SLIDESMANIA.COM

38
 Mucosal areas acquire a coarse appearance due to the accumulation of fibrin in the
absence of complete or partial plasminogen. For this reason, the term “ligneous”, which
means “woody” in Latin, is used.

● The term “ligneous periodontitis” was first defined by Gunhan et al. as a periodontal
disease characterized by membranous gingival overgrowth and severe bone loss due to
the accumulation of amyloid-like material.
SLIDESMANIA.COM
 FIBRIN DEPOSITION IN
WOUND SITE
SLIDESMANIA.COM
 CLINICAL FEATURES
SLIDESMANIA.COM
 oGingival tissue appear fragile and bleed after tooth
brushing, gingival hyperplasia and fibrous nodules also
noted.
SLIDESMANIA.COM

42
 oHypermobility of temporomandibular joint
often results in dislocation of jaw.
SLIDESMANIA.COM

43
 CHEDIAK HIGACHI SYNDROME

o Autosomal recessive immunodeficiency disorder

characterized by abnormal intracellular protein
transport.
o Severe gingivitis and rapid loss of attachment, leading
to exfoliation of the teeth is seen.

oPeriodontal breakdown
occurs due to defective
leukocyte function.
SLIDESMANIA.COM

44
 CHEDIAK HIGACHI SYNDROME
SLIDESMANIA.COM

45
 LEUKOCYTE ADHESION DEFICIENCY (LAD)

o It is of two types: LAD I and LAD II

o Autosomal recessive disorder, occurs by
mutation in the gene encoding for CD 18 integrin
(LAD I) and CD 15 integrin (LAD II).
o The defective or absent expression of these
molecules on the surface of leukocytes
decreases their ability to adhere to endothelial
cells and to migrate to sites of infection.
SLIDESMANIA.COM

46
 oClinical features usually present in infancy
consist of recurrent, indolent bacterial
infections of the skin, mouth, & the
respiratory tract.
oSevere gingivitis with an early loss of primary
teeth, followed by the early loss of secondary
teeth, is seen.
oSevere form of periodontitis is seen that
does not require specific periodontal
pathogens because of entrapment of
neutrophils within the blood vessel.
SLIDESMANIA.COM

47
 Downs Syndrome
o Trisomy of chromosome 21
o Periodontal disease in Down
syndrome is characterized by
formation of deep pockets
associated with plaque
accumulation and moderate
gingivitis.
o This is due to;
− a reduced resistance to
infections

− a defect in T-cell maturation and

polymorphonuclear leukocyte
chemotaxis.
SLIDESMANIA.COM

48
 Hypophosphatasia

o Both autosomal dominant and recessive inheritance

o Associated with mutation in alkaline Phosphatase gene (
Ip36. Ip34).
o Includes cemental hypoplasia, aggressive periodontitis,
premature loss of 1º and 2º teeth.
SLIDESMANIA.COM

49
 Hypophosphatasia

o Both autosomal dominant and recessive inheritance

o Associated with mutation in alkaline Phosphatase gene (
Ip36. Ip34).
o Includes cemental hypoplasia, aggressive periodontitis,
premature loss of 1º and 2º teeth.
SLIDESMANIA.COM

50
 Gene Therapy
o Use of purified preparations of a gene or a fraction of
a gene, to treat diseases.
o There are four approaches:

a. A normal gene inserted to compensate for a nonfunctional gene.

b. An abnormal gene swapped for a normal gene.

c. An abnormal gene repaired through selective reverse mutation.

d. Change the regulation of gene pairs.

SLIDESMANIA.COM

51
 Gene therapy in Periodontics

1. Protein based approach

2. Cell based approach
3. Gene- delivery approach

-In vivo gene Delivery

-Ex vivo gene delivery

SLIDESMANIA.COM

52
 Clinical Utility of Genetics in
Periodontics
• Role of host gene in the etiology and pathogenesis of
the periodontal disease is just begun to be
understood.
• Association between polymorphisms in IL-1 genes and
severity of periodontitis has been described as a
major breakthrough in clinical practice.
SLIDESMANIA.COM

53
 o The clinical test for such a genetic risk has been proposed as a
component of the risk assessment profile for chronic periodontitis
that can be used to provide a rationale for explaining individual patient
susceptibility, providing early preventive or therapeutic intervention,
and allowing superior prognostic capabilities.
SLIDESMANIA.COM

54
 thank you!
Do you have any questions?
hello@mail.com
555-111-222
mydomain.com
SLIDESMANIA.COM
 REFERENCES
https://www.slideshare.net/slideshow/genetics-and-
periodontal-diseases/258620902#43
https://www.slideshare.net/slideshow/ligneous-periodontitispptx-periodontics/267231251

Principles of Genetics by Snustad

Genetics from genes to genome by Hartwell

SLIDESMANIA.COM