CHAPTER 4

EXTENSIONS OF MENDELIAN
GENETICS

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Chapter 4 – Outline and Learning

Objectives
1. Alleles Alter Phenotypes in Different Ways
2. Geneticists Use a Variety of Symbols for Alleles
3. Neither Allele Is Dominant in Incomplete, or Partial, Dominance
4. In Codominance, the Influence of Both Alleles in a Heterozygote Is Clearly Evident
5. Multiple Alleles of a Gene May Exist in a Population
6. Lethal Alleles Represent Essential Genes
7. Combinations of Two Gene Pairs with Two Modes of Inheritance Modify the 9:3:3:1 Ratio
8. Phenotypes Are Often Affected by More Than One Gene
9. Complementation Analysis Can Determine if Two Mutations Causing a Similar Phenotype
Are Alleles of the Same Gene
10. Expression of a Single Gene May Have Multiple Effects
11. X-Linkage Describes Genes on the X Chromosome
12. In Sex-Limited and Sex-Influenced Inheritance, an Individual’s Sex Influences the
Phenotype
13. Genetic Background and the Environment May Alter Phenotypic Expression
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  Gene expression does not always follow a simple dominant/recessive
mode, or more than one pair of genes can influence the expression of a
single character,
 classic 3:1 and 9:3:3:1 F2 ratios usually modified
 Two postulates are basic principles of gene transmission
 Genes are present on homologous chromosomes
 Chromosomes segregate and assort independently
 Gene interaction: single phenotype is affected by more than one set of
genes
 X-Linkage: genes that are present on the X chromosome

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I- Alleles Alter Phenotypes in

Different Ways

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 I.1- Alleles

 Alleles: Alternative forms of a gene

 Mutation: Ultimate source of alleles
 New phenotypes result from changes in functional activity of gene product
 Eliminating enzyme function
 Changing relative enzyme efficiency
 Changing overall enzyme function
 Wild-type (w t) allele: Occurs most frequently in nature and is usually, but not always,
dominant

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I.2- Function Mutations

 Loss-of-function mutations
 New phenotype results from change in activity
 Mutation causes loss of wild-type function
 Gain-of-function mutations
 Mutation enhances function of wild type
 Quantity of gene product increases
 Neutral mutations
 No change to the phenotype
 No change to the evolutionary fitness of the organism

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 II- Geneticists Use a Variety of
Symbols for Alleles

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II.1- Geneticists Use Symbols for Alleles

 Dominant alleles indicated by either an italic uppercase letter (D) or letters (Wr)
 Recessive alleles indicated by either an italic lowercase letter (d) or an italic letter or
group of letters (wr)
 Mutant alleles indicated by italic letter (e)
 Wild type alleles indicated by italic letter plus superscript + (e+)

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 II.2- Representing Alleles in Drosophila
melanogaster
 Another useful system was developed in genetic studies of the fruit fly Drosophila
melanogaster to discriminate between wild-type and mutant traits
 initial letter, or a combination of several letters, from the name of the mutant trait.
 If the trait is recessive, lowercase is used; if it is dominant, uppercase is used.
 The contrasting wild-type trait is denoted by the same letters, but with a superscript +
 Example: Body color
 Ebony mutant phenotype = e
 Normal gray (wild-type) = e+

e+/e+: gray homozygote (wild type) OR +/+: gray homozygote (wild type)
e+/e: gray heterozygote (wild type) +/e: gray heterozygote (wild type)
e/e: ebony homozygote (mutant) e/e: ebony homozygote (mutant)

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II.2- Representing Alleles in Drosophila

melanogaster
 Example: Wing shape
 Wrinkled mutant phenotype = Wr
 Normal wing (wild-type) = Wr+

Wr+/Wr+: normal homozygote (wild type) OR +/+: normal homozygote (wild type)
Wr+/Wr: Wrinkled heterozygote (mutant) +/Wr: Wrinkled heterozygote (mutant)
Wr/Wr: Wrinkled homozygote (mutant) Wr/Wr: Wrinkled homozygote (mutant)

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 II.3- No Dominance

 If no dominance exists: italic uppercase letters and superscripts for alternative alleles
(R1/R2, CW/CR)

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III- Neither Allele is Dominant in

Incomplete, or Partial, Dominance

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 III.1- Incomplete or Partial Dominance

 Intermediate phenotype
 Neither allele is dominant

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III.2- Incomplete dominance in snapdragon

Phenotypic and genotypic ratios are

the same
Each genotype has its own phenotype
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 III.3- Intermediate Level of Gene Expression

Incomplete dominance in humans

 Example: Tay-Sachs disease
 Homozygous recessives affected by fatal lipid-storage disorder
 Disorder fatal for neonates
 Hexosaminidase A activity absent
 Enzyme involved in lipid metabolism
 Normal heterozygotes: one copy of mutant gene
 1/2 wt enzyme activity compared to homozygous normal noncarriers

 Threshold effect
 Normal phenotypic expression results
 Certain level (usually 50% or less) of gene product is attained
 In Tay-Sachs disease, < 50% threshold

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IV- In Codominance, the Influence of

Both Alleles in a Heterozygote is Clearly
Evident

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 IV.1- Codominance

 Codominance
 No dominance or recessiveness
 No incomplete or blending

 Joint expression of both alleles in a heterozygote

 Same ratios as incomplete dominance.

 Examples:
 Black cat x white cat → striped cat
 Blood groups A and B in humans (+ multiple alleles with blood type O)
 Blood groups M and N

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IV.2- MN blood group

Example of codominance in humans: MN Blood Group

 Autosomal (chromosome 4)
 Alleles LM and LN

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 V- Multiple Alleles of a Gene May
Exist in a Population

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V.1- Multiple Alleles

 Great amount of genetic information = can be modified in several ways

 Multiple alleles
 Three or more alleles of the same gene
 Resulting mode of inheritance unique
 Can only be studied in populations

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 V.2- ABO Blood Groups

 Gene on chromosome 9
 Example of multiple alleles
 A and B antigens present on surface of red blood cells
 Three alleles of a single gene responsible for A B O phenotypes
 Gene I (=isoagglutinogen) : alleles IA, IB, i
 IA and IB allele: Produce their respective antigens
 i allele: Does not produce antigen
 IA and IB are dominant to i
 IA and IB are codominant to each other

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V.2- ABO Blood Groups

 Purpose?
 Compatibility tests for blood transfusions
 Used to disprove (but not prove) paternity

 A and B antigens
 Carbohydrate groups bound to lipid groups on red blood cells

 H substance
 One or two terminal sugars are added
 O blood types (ii) only have the H substance protruding from red blood cells

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 V.3- The white locus in Drosophila

 white mutation in eye color= 1 out of 100 possible alleles

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VI- Lethal Alleles Represent

Essential Genes

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 VI.1- Essential, Dominant, and Recessive
Lethal Alleles
 Essential genes
 Absolutely required for survival
 Loss-of-function mutations cause death, but can be tolerated as heterozygous IF
one wild-type allele sufficient for survival (threshold effect)
 Homozygous recessive will not survive
 Mutation behaves as recessive lethal allele
 Lethal allele
 Has potential to cause death of organism – life expectancy dependent on timing
when product becomes essential
 Alleles are result of mutations in essential genes
 Inherited in recessive manner

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VI.1- Essential, Dominant, and Recessive

Lethal Alleles
 Sometimes can cause different phenotype in heterozygotes
 Agouti gene in mice/rabbits/etc. (coat color)
 Agouti allele A
 Mutant yellow allele AY
 Behaves dominantly to normal allele to control coat color

 Behaves as homozygous recessive lethal allele

 Genotype AY AY does not survive

 In Drosophila: Curly wing (Cy), Plum eye (Pm), Dichaete wing (Dw), Stubble bristle (Sb), Lyra
wing (Ly)
 Tailless Manx cats

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VI.1- Essential, Dominant, and Recessive

Lethal Alleles
 Sometimes one allele not enough for survival:
 Loss-of-function mutation – one allele not enough (Threshold effect)
 Gain-of-function mutation – interferes with normal function of wt allele
 Dominant lethal allele
 Presence of one copy of allele results in death
 Usually caused by de novo mutations
 Huntington disease
 Dominant autosomal allele H
 Onset of disease in heterozygous delayed until adulthood (~40yo)
 Characterized by progressive degeneration of nervous system, dementia, and early
death
 Affected individuals (Hh) – 50% chance of transmitting to offspring
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 VII- Combinations of Two Gene Pairs
with Two Modes of Inheritance Modify
the 9:3:3:1 Ratio

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 Modification of Mendel’s 3 : 1 monohybrid ratio ⇒ modification of the 9 : 3 : 3 : 1 ratio if

combined in dihybrid cross
 Different modes of inheritance combined
 Results in many variants of modified ratios
 As long as genes are on separate chromosomes
 Example: Two heterozygotes mate
 Both autosomal recessive for albinism
 Albinism inherited Mendelian style

 Both blood type A B

 Blood types via three multiple alleles, IA, IB, and ii (codominance)

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VIII- Phenotypes are Often

Affected by More Than One Gene

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  After rediscovery of Mendel’s work, experimentation showed greater complexity
 Phenotypic characters are influenced by many different genes and their products
 Gene interaction
 Several genes influence a particular characteristic
 Not necessarily by direct interaction of the gene products
 Cellular function of numerous gene products contributes to development of
common phenotype

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VIII.1- Epistasis

 Greek, meaning interruption

 Type of gene interaction where the expression of one gene masks or modifies the
effect of a second gene
 In an antagonistic manner, which leads to masking
OR
 In a complementary, or cooperative, fashion

 Eg. Bombay Phenotype

 hh masks alleles on locus I
 hh is epistatic and locus I is hypostatic

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 VIII.2- Epistasis example – Blood types

 Bombay phenotype
 Homozygous recessive condition
 First locus masks expression of second locus
 Mutant FUT1 gene masks expression of IA and IB alleles
 A or B antigen forms only when individual has one wild-type allele

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 VIII.2- Epistasis example – Blood types

 Bombay phenotype
 1952 : Type O female, yet…
 One parent has type A B blood and
 Female is IB allele donor to two children

 Female found to be homozygous for F U T 1 at the fucosyl transferase locus

 Prevents her from producing H substance
 No substrate to make A or B antigens
 Results functionally in type O
 Can only receive Bombay type blood

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 VIII.2- Epistasis example – Blood types

 Key difference with the modified dihybrid cross on slide 31:

 only one character—blood type—is being followed vs. blood type and skin pigmentation are
followed as separate phenotypic characteristics.
 Even though a single character is followed, the phenotypic ratio is /16.
 Even without knowing about substance H, a second gene pair is necessarily involved.

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VIII.3- Effects of Epistasis

 Relationships between alleles and genes can vary greatly and affect the phenotypes
in many ways.
 Genotypic ratios will be identical to Mendel’s predictions, but phenotypic ratios vary.
 Epistasis is not necessarily due to a direct interaction between gene products.
 Eg. Hereditary deafness
 Ear forms as result of many genes
 Genes interact to produce common phenotype
 Mutations interrupt development  hereditary deafness
 Mutant phenotype
 heterogeneous trait where many genes are involved

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 VIII.3- Effects of Epistasis

 In the following examples, several assumptions and conventions:

1. Distinct phenotypic classes are produced, each clearly discernible from all others.
2. Genes are on separate chromosomes and segregate independently
3. In most case, complete dominance is assumed for each locus, which allows to use A- for AA
or Aa without any difference in phenotype.
4. Following the cross of true-breeding parents (AABB x aabb; AAbb x aaBB), the resulting F1 is
heterozygous AaBb; and the F2 presents the following genotypic ratios:
9/16 A- B-
3/16 A- bb
3/16 aa B-
1/16 aa bb

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VIII.4- Recessive epistasis

 Typical ratios (in case of complete dominance at each locus):

9:4:3
 Eg.: Coat color in mice
 B allele: black pigment
 bb genotype: all black
 C genotype: pigment is deposited on the hair
 Cc genotype: no pigment (whatever color)
 Mouse is albino

 cc genotype MASKS expression of B/b alleles = recessive epistasis

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VIII.4- Recessive epistasis

 Eg: Albinism in humans

 Melanin density and deposition in skin, hair, etc. is under the control of many genes.
 Enzyme Tyrosinase in necessary for melanin production, encoded by allele A.
 Allele a codes for a non-functional enzyme.
 Homozygotes aa do not produce melanin, which masks the effect of all other color genes
 = Albinism

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 VIII.5- Dominant Epistasis

 Dominant allele at one locus masks an allele at second locus

 Typical ratios (in case of complete dominance at each locus):
12:3:1
 Eg: Summer squash fruit color
 Gene W determines presence (ww) or absence (W-) of color
 Gene G determines green(gg) or yellow (G-) color
WwGg x WwGg

WG Wg wG wg
WG WWGG WWGg WwGG WWgg
Wg WWGg WWgg WwGg Wwgg
wG WwGG WwGg wwGG wwGg
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VIII.6- Complementary Gene Interaction

 First discovered by William Bateson and Reginald Punnett (of Punnett square fame), in
a cross between two true-breeding strains of white-flowered sweet peas
 Typical ratios (in case of complete dominance at each locus):
9:7
 Cross between two true-breeding strains of white-flowered sweet peas
 All purple F1 plants
 F2 plants in a ratio of 9/16 purple to 7/16 white

PC Pc pC pc
Precursor Intermediate Anthocyanin PC PPCC PPCc PpCC PpCc
product
Pc PPCc PPcc PcCc Ppcc
C P pC PpCC PPCc ppCC ppCc
pc PpCp Ppcc ppCc ppcc
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 VIII.7- Double dominant epistasis

 Complete dominance for each locus. A dominant allele at any locus masks the
phenotype of the other.
 Typical ratios (in case of complete dominance at each locus):
15:1
 Wheat color: 2 enzymes encoded by different genes able to convert the same
precursos into colored pigment.
 Only recessive homozygote is white
 Can be due to gene duplication
AB Ab aB ab
A AB AABB AABb AaBB AaBb
Precursor Pigment Ab AABb Aabb AaBa Aabb

B aB AaBB AaBb aaBB aaBb

ab AaBb Aabb aaBb aabb

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VIII.8- Suppressive dominant epistasis

 Complete dominance for each locus. A dominant allele at any locus masks the
phenotype of the other.
 Typical ratios (in case of complete dominance at each locus):
13:3
 Primula flower color.
 Enzyme K produces malvidin (blue pigment)
 Allele D encodes an inhibitor of K
 Blue requires K- and dd

KD Kd kD kd

Pigment KD KKDD KKDd KkDD KkDd

K X Malvidin Kd KKDd KKdd KkDd Kkdd
kD KkDD KkDd kkDD kkDd
D
kd KkDd Kkdd kkDd kkdd 50
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 VIII.9- Double interaction (Novel phenotypes)

 Several types of interactions can lead to new phenotypes.

 Eg.1: both gene pairs influence fruit shape equally.
 Typical ratios (in case of complete dominance at each locus):
9:6:1
 Fruit shape of summer squash
 Disc fruits require dominant alleles at both loci (A-B-)
 Sphere fruits require dominant allele at one/either locus (A-bb or aaB-)
 Long fruits occur when no dominant alleles at either locus (aabb)
AB Ab aB ab
AB AABB AABb AaBB AaBb
Ab AABb Aabb AaBa Aabb
aB AaBB AaBb aaBB aaBb
ab AaBb Aabb aaBb aabb
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VIII.9- 9:3:3:1 ratio and epistasis

 Eg: chicken combs (Bateson and Punnet)

 “rose”-combed rooster x “pea”-combed hen
 F1 100% “walnut” (new phenotype)
 F2: walnut:rose:pea:single in 9:3:3:1 ratio
 Dihybrid ratio but 1 feature

RP Rp rP rp
RP RRPP RRPp RrPP RrPp
Rp RRPp RRpp RrPp Rrpp
rP RrPP RrPp rrPP rrPp
rp RrPp Rrpp rrPp rrpp
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 VIII.9- 9:3:3:1 ratio and epistasis

 Eg: Eye color in Drosophila

 The wild-type eye color is due to the deposition and mixing of pigments
 Each step of each pathway is catalyzed by a separate enzyme and is thus under the control of
a separate gene

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 IX- Complementation Analysis

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IX.1- Complementation Analysis

 Complementation analysis
 Screens number of individual mutations resulting in same phenotype
 Can predict total number of genes determining a trait
 Complementation group
 All mutations present in any single gene

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 IX.2- Example in Drosophila

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X- Pleiotropy
Expression of a Single Gene May Have Multiple Effects

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 X.1- Definition

 Expression of single gene has multiple phenotypic effects

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X.2- Examples of human diseases

 Marfan syndrome
 Single autosomal dominant mutation in gene that encodes protein fibrillin
 widespread in many tissues in the body
 important to the structural integrity of the lens of the eye, to the lining of vessels such as the aorta, and
to bones
 Symptoms include lens dislocation, increased risk of aortic aneurysm, and lengthened long
bones in limbs

 Porphyria variegate
 Autosomal disorder
 Toxic buildup of porphyrins (component of hemoglobin) in body, esp. brain
 Numerous phenotypic effects
 Abdominal pain, muscular weakness, fever, racing pulse, insomnia, vision issues, delirium, convulsions…

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 X.2- Examples of human diseases

 Phenylketonuria
 Deficiency in Phenylalanine hydroxylase (PAH) which converts Phe into Tyr
 Phe accumulates
 Brain toxicity = mental retardation
 Converted into phenylketones, excreted in urine
 Low levels of Tyr
 Halts melanin production = pigmentation defects

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X.2- Examples of human diseases

 Sickle-cell anemia

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 XI- X-Linkage

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XI.1- Sex Determination

 Sex of animals and plants determined by unlike chromosomes (often X and Y)

 Drosophila and humans
 Males: XY
 Females: XX
 Hemizygous: males XY
 Homozygous: females XX

 In birds, males are homozygous (ZZ) and females hemizygous (ZW)

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 XI.2- X-linkage

Y Chromosome
 Relatively inert genetically
 Male-specific genes on human Y chromosome
 Lacks copies of genes found on X chromosome

X-linkage
 Genes present on X chromosome exhibit specific patterns of inheritance
 Different from autosomal genes
 crisscross pattern of inheritance: in which phenotypic traits controlled by recessive X-
linked genes are passed from homozygous mothers to all sons

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XI.3- X-Linkage in Drosophila

 White eye mutation in Drosophila

 Wild-type red eye color is dominant to white
 Inheritance pattern of white eye related to sex of parent
 Described by Morgan: Reciprocal crosses between white- and red-eyed flies did not
yield identical results
 Explanation: white locus present on X chromosome (X-linked)

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 XI.4- X-Linkage in Humans

 Many genes and the respective traits controlled by them are recognized as being linked
to the X chromosome
 Color blindness: X chromosome-linked
 Red/green color blindness
 Mother passes to all sons
 Mother passes to no daughters

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XI.4- X-Linkage in Humans

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 XI.4- X-Linkage in Humans

 Why more frequent in males?

 Only need 1 allele to develop the disease (hemizygous)
 If disease is debilitating or lethal before sexual maturity: only source of mutated alleles are
heterozygous females
 DMD starts at 6 and lethal by 20

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XII- Sex-Limited and Sex-Influenced

Inheritance

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 XII.1- Definition

 Sex-limited inheritance
 Expression of specific phenotype is absolutely limited to one sex
 Sex-influenced inheritance
 Sex of individual influences expression of phenotype
 Not limited to one sex or the other

 In both cases, autosomal genes but their phenotypic expression is dependent on the
gender.

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XII.2- Sex-limited inheritance

Eg. Feather plumage in chickens

 Caused by an autosomal gene
 Hen-feathering controlled by dominant allele expressed in
both sexes
 Cock-feathering controlled by recessive allele only
expressed in males
 But actual expression can be modified by the individual’s
sex hormones

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 XII.2- Sex-limited inheritance

Eg. Feather plumage in chickens

 In certain breeds, one allele has become fixed in the

population
 Leghorn race are all hh => male/female differences
 Sebright bantams (miniature chickens) are all HH => no
male/female differences

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XII.2- Sex-limited inheritance

Eg. Milk production in dairy cattle

 autosomal genes responsible for milk yield
 obviously expressed only in females

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 XII.3- Sex-Influenced Inheritance

 Autosomal genes responsible for the contrasting phenotypes

 Trait may be displayed by both males and females
 Expression of these genes is dependent on the hormone constitution
 Heterozygous genotype exhibits one phenotype in one sex and the contrasting one in
the other.

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XII.3- Sex-Influenced Inheritance

Eg. Pattern Baldness

 Bald phenotype is much more prevalent in males.

 When females do inherit the BB genotype, the
phenotype is less pronounced than in males and is
expressed later in life

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 XII.3- Sex-Influenced Inheritance

Eg. Horn formation in certain breeds of sheep (Dorset Horn sheep)

Eg. Certain coat patterns in cattle

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XIII- Genetic Background and the

Environment May Alter Phenotypic
Expression

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 XIII.1- Phenotypic Expression

 Phenotypic expression of trait

 Influenced by environment
 Influenced by genotype
 Gene products function within cell in various ways
 Organism exists in diverse environmental conditions

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XIII.2- Penetrance and Expressivity

 Penetrance
 Percentage of expression of the mutant genotype in a population
 “All-or-nothing”
 Can depend on numerous factors (environment, age, other genes, etc.
 E.g. penetrance for Huntington’s is 60% at 50, 100% at 70

 Expressivity
 Range of expression of mutant phenotype
 Severity of symptoms for same disease
 Result of genetic background differences and/or environmental effects

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 XIII.2- Penetrance and Expressivity

 Expressivity example: Eyeless mutation in Drosophila

 Homozygous recessive mutant gene
 Phenotype ranges from presence of normal eyes to absence of one or both eyes

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XIII.3- Genetic Background

 The impact of the collective genome of an organism on the expression of a gene

under investigation
 Difficult to assess
 One clearly characterized: position effect
 Physical location of gene influences expression
 Translocation or inversion events modify expression
 Gene relocated to condensed or genetically inert chromosome (heterochromatin)

a) (a) Female heterozygote for white eye genotype showing normal dominant phenotype
b) (b) Chromosomal rearrangement leads to variegated effect (also female heterozygote for white eye)

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 XIII.3- Genetic Background

 Genetic suppression
 Effect of one mutant gene countered by effect of a second mutant gene

 E.g. in Drosophila: suppressor of sable (su-s), suppressor of forked (su-f), and suppressor of Hairy-
wing (su-Hw)

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XIII.4- Conditional mutations – Temperature

effects
 Evening primrose
 Red flowers at 23C
 White flowers at 18C
 Siamese cats and Himalayan rabbits
 Darker fur on cooler areas of body (tail, feet, ears)
 Enzymes lose catalytic function at higher temperature

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 XIII.4- Conditional mutations – Temperature
effects
 Temperature-sensitive mutations
 Viruses, bacteria, fungi, and Drosophila
 Mutant allele expresses mutant phenotype (or even die if lethal mutations) at one
temperature (=restrictive temperature), wild-type phenotype at another (=permissive)
 Useful when studying phage (bacterial virus) mutants
 Studying viral genetics:
 Temperature-sensitive mutations are easily induced and isolated in viruses

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XIII.5- Nutritional Effects

 Nutritional mutations
 Prevent synthesis of nutrient molecules in microbes
 Auxotrophs (microbe)
 Phenotype expressed or not depending upon diet
 Phenylketonuria
 Loss of enzyme to metabolize amino acid phenylalanine
 Severe problems unless low-Phe diet
 Galactosemia
 Cannot metabolize galactose
 Lactose intolerance
 Cannot metabolize lactose

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 XIII.6- Onset of Genetic Expression

 Age at which genotype is expressed in the phenotype

 In most cases, depends on events during the normal sequence of growth and development
 Prenatal, infant, preadult, adult phases require different genetic information
 Tay-Sachs disease
 Inherited autosomal recessive
 Lethal lipid-metabolism disease (hexosaminidase A)
 Baby normal for a few months, dies by age 3
 Lesch–Nyhan syndrome
 Inherited X-linked recessive
 Abnormal nucleic acid metabolism [Purine salvage enzyme defect (H PRTase)]
 Normal for about 6 months

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XIII.6- Onset of Genetic Expression

 Duchene muscular dystrophy (D MD)

 X-linked recessive disorder
 Diagnosis at 3–5 years old, fatal by early 20s
 Huntington disease
 Variable age of onset in humans
 Autosomal dominant disorder
 Affects frontal lobes of cerebral cortex
 Progressive cell death—brain deterioration
 Age range 30–50 years old (mean 38)

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 XIII.7- Genetic Anticipation

 Genetic disease has earlier onset and increased severity with each succeeding
generation

 Eg. Myotonic dystrophy (DM1)

 Adult muscular dystrophy
 Autosomal dominant
 Increased severity and earlier onset with successive generations of inheritance

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XIII.7- Genetic Anticipation

 Genetic disease has earlier onset and increased severity with each succeeding
generation

 Eg. Myotonic dystrophy (DM1)

 Adult muscular dystrophy
 Autosomal dominant
 Increased severity and earlier onset with successive generations of inheritance
 Mutation due to high number of a trinucleotide repeat in DMPK1 gene
 Normal 5-35 copies
 Affected between 150 and 2000 copies
 Increase of repeated segment in successive generations

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 XIII.8- Genomic (Parental) Imprinting

 Selective gene silencing impacts phenotypic expression

 Silencing depends on parental origin of genes
 Silencing occurs in early development
 Regions of chromosome imprinted on one homolog but not the other

 Importance of DNA methylation and other epigenetic modifications

 Methyl groups (CH3) added to 5 carbon of Cytosine
 High levels of methylation inhibit gene activity
 Active genes are undermethylateD

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 XIII.8- Genomic (Parental) Imprinting

 In humans:

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