Extensions of Mendelian Genetics

Chapter
4
Extensions of
Mendelian Genetics
Lecture Presentation by
Dr. Cindy Malone,
California State University Northridge
© 2017 Pearson Education, Ltd.

Chapter 4 Contents
4.1 Alleles Alter Phenotypes in Different Ways

4.2 Geneticists Use a Variety of Symbols for Alleles
4.3 Neither Allele Is Dominant in Incomplete, or Partial,
Dominance
4.4 In Codominance, the Influence of Both Alleles in a
Heterozygote Is Clearly Evident
4.5 Multiple Alleles of a Gene May Exist in a Population
4.6 Lethal Alleles Represent Essential Genes
4.7 Combinations of Two Gene Pairs Involving Two
Modes of Inheritance Modify the 9:3:3:1 Ratio
Continued

Chapter 4 Contents
4.8 Phenotypes Are Often Affected by More Than One

Gene
4.9 Complementation Analysis Can Determine if Two
Mutations Causing a Similar Phenotype Are Alleles
4.10 Expression of a Single Gene May Have Multiple
Effects
4.11 X-Linkage Describes Genes on the X Chromosome
4.12 In Sex-Limited and Sex-Influenced Inheritance, an
Individual's Sex Influences the Phenotype
4.13 Genetic Background and the Environment May Alter
Phenotypic Expression

Extensions of Mendelian Genetics
 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

4.1 Alleles After Phenotypes in Different
Ways

Section 4.1: Alleles Alter Phenotypes
 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 (wt) allele: Occurs most frequently in

nature and is usually, but not always, dominant

Section 4.1: 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

4.2 Geneticists Use a Variety of Symbols
for Alleles

Section 4.2: 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 with the  superscript (Wr)

Section 4.2: Representing Alleles in
Drosophila melanogaster
 Example: Body color
– Ebony mutant phenotype is indicated by e
– Normal gray (wild-type) is indicated by e

Section 4.2: Allele Representations
Example of Drosophila alleles
 e/e: gray homozygote (wild type)

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

Section 4.2: No Dominance
 If no dominance exists, italic uppercase letters

and superscripts are used to denote alternative
alleles (R1, R2, CW, CR)

4.3 Neither Allele Is Dominant in
Incomplete, or Partial, Dominance

Section 4.3: Incomplete or Partial Dominance
 Incomplete or partial dominance

– Intermediate phenotype
– Neither allele is dominant

Section 4.3: Snapdragons
 Incomplete dominance in snapdragon
 Example: Red snapdragon crossed with white

snapdragon
– F1 offspring: pink flowers
– F2 generation: 1/4 red, 1/2 pink, 1/4 white
– Phenotypic and genotypic ratios are the same
 Each genotype has its own phenotype

© 2017 Pearson Education, Ltd. Figure 4-1
Section 4.3: 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
– Hexosaminidasem A activity absent
 Enzyme involved in lipid metabolism
– Normal heterozygotes: One copy of mutant gene
 1/2 wt enzyme activity compared to homozygous
normal non-carriers

Section 4.3: Threshold Effect
 Threshold effect
– Normal phenotypic expression results
– Certain level (usually 50% or less) of gene
product is attained
– In Tay-Sachs disease,  50% threshold

4.4 In Codominance, the Influence of Both
Alleles in a Heterozygote Is Clearly Evident

Section 4.4: Codominance
 Codominance
– No dominance or recessiveness
– No incomplete or blending
– Joint expression of both alleles in a heterozygote

Section 4.4: MN Blood Group
Example of codominance in humans

MN Blood Group
 Alleles LM and LN
Genotype Phenotype
LM LM M
LM LN MN
LN LN N

4.5 Multiple Alleles of a Gene May Exist in a
Population

Section 4.5: Multiple Alleles
 Multiple alleles
– Three or more alleles of the same gene
– Resulting mode of inheritance unique
– Can only be studied in populations

Section 4.5: ABO Blood Groups
 Human ABO blood groups

– Example of multiple alleles
– A and B antigens present on surface of red blood
cells
– Three alleles of a single gene responsible for
ABO phenotypes

Section 4.5: “I” Isoagglutinogen (Antigen)
 Three alleles designed:

– IA allele
– IB allele
– i allele
 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

Section 4.5: A and B Antigens
 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

Section 4.5: Bombay Phenotype
Bombay phenotype
 Type O female, yet…
– one parent has type AB blood and
– female is IB allele donor to two children
 Female found to be homozygous for FUT1 at the

fucosyl transferase locus
– Prevents her from producing H substance
– No substrate to make A or B antigens
– Results functionally in type O
Bombay Pedigree
Family pedigree showing inheritance of Bombay

allele

4.6 Lethal Alleles Represent Essential
Genes

Section 4.6: Essential, Dominant, and
Recessive Lethal Alleles
 Essential genes
– Absolutely required for survival
– Mutations can be tolerated if heterozygous
 One wild-type allele sufficient for survival
 Homozygous recessive will not survive
– Mutation behaves as recessive lethal allele

Section 4.6: Lethal Allele
 Lethal allele
– Has potential to cause death of organism
– Alleles are result of mutations in essential genes
– Inherited in recessive manner
 Dominant lethal allele
– Presence of one copy of allele results in death
– Example: Huntington disease

Section 4.6: Huntington Disease
 Huntington disease
– Dominant autosomal allele H
– Onset of disease in heterozygous delayed until
adulthood
– Characterized by progressive degeneration of
nervous system, dementia, and early death

Section 4.6: Molecular Basis of Dominance,
Recessive, and Lethality
 Agouti gene in mice (coat color)
– Agouti allele A
– Mutant yellow allele AY
 Mutant allele (AY)
– Behaves dominantly to normal allele to control
coat color
– Behaves as homozygous recessive lethal allele
 Genotype AY AY does not survive

4.7 Combinations of Two Gene Pairs with
Two Modes of Inheritance Modify the
9:3:3:1 Ratio

Section 4.7: Two Modes of Inheritance
Occurring Simultaneously
 Different modes of inheritance combined
– Results in many variants of modified ratios
 Example:
– Two heterozygotes mate
– Both autosomal recessive for albinism
– Both blood type AB
– Albinism inherited Mendelian style
– Blood types via three multiple alleles, IA, IB, and ii

4.8 Phenotypes Are Often Affected by More
Than One Gene

Section 4.8: Phenotypic Characters
 Phenotypic characters are influenced by many

different genes and their products
 Gene interaction
– Several genes influence a particular
characteristic
– Cellular function of numerous gene products
contributes to development of common phenotype

Section 4.8: Epistasis
 Epistasis
– Expression of one gene masks/modifies effect of
another gene pair
– Gene masks phenotypic effects of another gene
– Each step of development increases complexity
of organ
– Under control and influence of many genes

Section 4.8: Hereditary Deafness
 Epistasis and multiple gene interaction:

Hereditary deafness
– Ear forms as result of many genes
– Genes interact to produce common phenotype
– Mutations interrupt development  hereditary
deafness
– Mutant phenotype (heterozygous trait)

Section 4.8: 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 and B antigen forms only when individual has
one wild-type allele

Section 4.8: Effects of Epistasis
 Gene interaction reveals inheritance patterns

 Epistasis has effect on one or more of four
phenotypic categories (Figure 4-7)

Section 4.8: Recessive Epistasis
 Recessive epistasis
– B allele: black pigment
– A allele: agouti phenotype
– aa genotype: all black
– bb genotype: no black pigment, even if A or a
alleles present
 Mouse is albino
– bb genotype MASKS expression of A allele 

recessive epistasis

Section 4.8: Dominant Epistasis
 Dominant epistasis
– Dominant allele at one loci masks an allele at
second loci
 Example: Summer squash fruit color

– Dominant allele A  White fruit
 Regardless of second loci allele
– Absence of A allele  Yellow fruit
 Genotypes aa, BB, Bb  yellow fruit
 Genotype bb  green

Section 4.8: Novel Phenotypes: Fruit Shape in
Summer Squash
 Disc-shaped fruit (AABB) crossed with long fruit
(aabb)
 F1: all disc-shaped fruit
 F2: includes parental phenotypes and spherical
variants in 9:6:1 ratio
– 9/16 A-B- disc
– 3/16 A-bb sphere, 3/16 aaB- sphere
– 1/16 aabb long

Section 4.8: Alleles and Loci
 Disc fruits
– Require dominant alleles at both loci
 Sphere fruits
– Require dominant allele at one/either locus
 Long fruits
– Occur when no dominant alleles at either locus

4.9 Complementation Analysis Can
Determine if Two Mutations Causing a
Similar Phenotype Are Alleles of the Same
Gene

Section 4.9: 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

4.10 Expression of a Single Gene May Have
Multiple Effects

Section 4.10: Pleiotropy
 Pleiotropy
– Expression of single gene has multiple phenotypic
effects
 Example: Marfan syndrome

– Single autosomal dominant mutation in gene that
encodes protein fibrillin results in multiple
phenotypic effects

Section 4.10: Pleiotropy
 Example: Porphyria variegata

– Autosomal disorder
– Toxic buildup of porphyrins in body
– Numerous phenotypic effects
 Abdominal pain
 Muscular weakness
 Fever
 Racing pulse
 Insomnia
 Vision issues

4.11 X-Linkage Describes Genes on the
X Chromosome

Section 4.11: Sex Determination
 Sex of animals and plants determined by unlike

chromosomes X and Y
 Drosophila and humans

– Males: XY
– Females: XX
 Hemizygous: males XY
 Homozygous: females XX

Section 4.11: X-linkage
 X-linkage
– Genes present on X chromosome exhibit patterns
of inheritance
– Different from autosomal genes
 Y chromosome
– Relatively inert genetically
– Male-specific genes on human Y chromosome
– Lacks copies of genes found on X chromosome

Section 4.11: 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
 Reciprocal crosses between white- and red-eyed
flies did not yield identical results
 White locus present on X chromosome (X-linked)

Section 4.11: X-linked in Humans
 Color blindness: X chromosome-linked

– Red/green color blindness
– Mother passes to all sons
– Mother passes to no daughters
– Figure 4-14

© 2017 Pearson Education, Ltd. Table 4.2
Section 4.11: Lethal X-linked Recessive
 Lethal X-linked recessive disorders

– Observed only in males
– Females can only be heterozygous carriers who
do not develop the disorders
 Example: Duchenne muscular dystrophy
– Onset prior to age 6
– Lethal around age 20
– Occurs only in males

4:12 In Sex-Limited and Sex-Influenced
Inheritance, an Individual’s Sex Influences
the Phenotype

Section 4.12: Sex Influences Phenotype
 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

Section 4.12: Sex Influences Phenotype
 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

Section 4.12: Male Pattern Baldness
 Allele B behaves dominant in males and

recessive in females
 In BB genotype in females, phenotype is less
pronounced

4.13 Genetic Background and the
Environment May Alter Phenotypic
Expression

Section 4.13: 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

Section 4.13: Penetrance and Expressivity
 Penetrance
– Percentage of expression of the mutant genotype
in a population
 Expressivity
– Range of expression of mutant phenotype
– Result of genetic background differences and/or
environmental effects

Section 4.13: Expressivity
 Eyeless mutation in
Drosophila
– Homozygous recessive
mutant gene
– Phenotype ranges from
presence of normal eyes
to absence of one or both
eyes

Section 4.13: Genetic Background
 Genetic background: Position effect

– Physical location of gene influences expression
– Translocation or inversion events modify
expression
– Gene relocated to condensed or genetically inert
chromosome (heterochromatin)

Section 4.13: Genetic Background
Position effect
a) Female heterozygote for
white eye genotype
showing normal
dominant phenotype
b) Chromosomal
rearrangement leads to
variegated effect (also
female heterozygote for
white eye)

Section 4.13: 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

Section 4.13: Temperature Sensitive
 Temperature-sensitive mutations
– Viruses, bacteria, fungi, and Drosophila
– Mutant allele expresses mutant phenotype at one
temperature, wild-type phenotype at another
– Useful when studying phage (bacterial virus)
mutants
 Studying viral genetics:
– Temperature-sensitive mutations are easily
induced and isolated in viruses

Section 4.13: 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
Section 4.13: Nutritional Effects
 Galactosemia
– Can not metabolize galactose
 Lactose intolerance
– Can not metabolize lactose

Section 4.13: Onset of Genetic Expression
Delayed onset of phenotypic expression

 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
– Purine salvage enzyme defect (HPRTase)
– Normal for about 6 months
Section 4.13: Onset of Genetic Expression
 Duchene muscular dystrophy (DMD)

– X-linked recessive disorder
– Diagnosis at 3–5 years old, fatal by age 20
 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
Section 4.13: Genetic Anticipation
 Genetic anticipation
– Genetic disease has earlier onset and increased
severity with each succeeding generation
 Example: Myotonic dystrophy (DM1)
– Adult muscular dystrophy
– Autosomal dominant
– Increased severity and earlier onset with
successive generations of inheritance

Section 4.13: Genomic (Parental) Imprinting
 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

Section 4.13: PWS vs. AS
 Prader-Willi syndrome (PWS)

– Parental segment is deleted
– Undeleted maternal chromosome remains
 Angelman syndrome (AS)
– Maternal segment is deleted
– Undeleted paternal chromosome remains
 The conditions exhibit different phenotypes

Section 4.13: DNA Methylation
 DNA methylation
– Involved in mechanism of imprinting and
epigenetic effects
– Methyl groups (CH3) added to 5 carbon
– High levels of methylation inhibit gene activity
– Active genes are undermethylated

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Chapter

© 2017 Pearson Education, Ltd.

4.1 Alleles Alter Phenotypes in Different Ways

© 2017 Pearson Education, Ltd.

4.8 Phenotypes Are Often Affected by More Than One

© 2017 Pearson Education, Ltd.

 Two postulates are basic principles of gene

 Gene interaction: single phenotype is affected

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

 Alleles: Alternative forms of a gene

 Wild-type (wt) allele: Occurs most frequently in

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

 Recessive alleles indicated by either an italic

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

Example of Drosophila alleles

 e/e: gray homozygote (wild type)

© 2017 Pearson Education, Ltd.

 If no dominance exists, italic uppercase letters

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

 Incomplete or partial dominance

© 2017 Pearson Education, Ltd.

 Incomplete dominance in snapdragon

 Example: Red snapdragon crossed with white

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

Example of codominance in humans

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

 Human ABO blood groups

© 2017 Pearson Education, Ltd.

 Three alleles designed:

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

 Female found to be homozygous for FUT1 at the

Family pedigree showing inheritance of Bombay

© 2017 Pearson Education, Ltd. Figure 4-3

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

 Phenotypic characters are influenced by many

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.

 Epistasis and multiple gene interaction:

© 2017 Pearson Education, Ltd.

© 2017 Pearson Education, Ltd.