Ch 4 Extensions of Mendelian Genetics

Two postulates are basic principles of gene transmission

– Genes are present on _____

– Chromosomes segregate and assort ______

• Gene interaction: single _____ is affected by more than one set of genes

• X-Linkage: genes that are present on the _____

• homologous chromosomes

• independently

• phenotype

• X chromosome

____: Alternative forms of a gene

____: Ultimate source of alleles

– New _____ result from changes in functional activity of gene product

▪ Eliminating enzyme function

▪ Changing relative enzyme efficiency

▪ Changing overall enzyme function

_____: Occurs most frequently in nature and is usually, but not always, dominant

• Alleles

• Mutation

• phenotypes

• Wild-type (wt) allele

______ mutations

– New phenotype results from change in activity

– Mutation causes loss of wild-type function

______ mutations

– Mutation enhances function of wild type

– Quantity of gene product increases

______ mutations

– No change to the phenotype

– No change to the evolutionary fitness of the organism

• Loss-of-function

• Gain-of-function

• Neutral

______ alleles indicated by either an italic uppercase letter (D) or letters (Wr)

_____ alleles indicated by either an italic lowercase letter (d) or an italic letter or group of letters (wr)

___ alleles indicated by italic letter (e)

_____ alleles indicated by italic letter plus superscript (e^+)

• Dominant

• Recessive

• Mutant

• Wild type

Allele Representations

.

_____ or _____ dominance

– Intermediate phenotype

– Neither allele is dominant

• Incomplete or partial

Incomplete dominance in humans

– Example: _____ disease

• Tay-Sachs

The minimum amount of gene product needed for normal phenotype expression, below which a disease phenotype appears:

• ____ effect

– Normal phenotypic expression results

– Certain level (usually 50% or less) of gene product is

attained

– In Tay-Sachs disease, < 50% threshold

• Threshold

_______

– No dominance or recessiveness

– No incomplete or blending

– Joint expression of both alleles in a heterozygote

• Codominance

_____ alleles

– Three or more alleles of the same gene

– Resulting mode of inheritance unique

– Can only be studied in populations

• Multiple

Human _____ blood groups

– Example of ____ alleles

– A and B antigens present on surface of red blood cells

– Three alleles of a single gene responsible for ABO phenotypes

• ABO

• multiple

Isoagglutinogen (Antigen)

_____ antigens

– Carbohydrate groups bound to lipid groups on red blood cells

• ____ substance

– One or two terminal sugars are added

– O blood types (___) only have this substance protruding from red blood cells

• A and B

• H

• ii

_____ phenotype

• Type O female, yet...

– One parent has type AB blood and

– Female is I^B allele donor to two children

• Female found to be homozygous for ____ at the fucosyl transferase locus

• Bombay

• FUT1

_____ 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 _______

• Essential

• recessive lethal allele

____ allele

– Has potential to cause death of organism

– Alleles are result of mutations in essential genes

– Inherited in recessive manner

_____ allele

– Presence of one copy of allele results in death

– Example: ______

• Lethal

• Dominant lethal

• Huntington disease

____ disease

– Dominant autosomal allele H

– Onset of disease in heterozygous delayed until adulthood

– Characterized by progressive degeneration of nervous system, dementia, and early death

• Huntington

____ gene in mice (coat color)

– Agouti allele A

– Mutant ____ allele A^Y

_____ allele (A^Y)

– Behaves dominantly to normal allele to control coat color

– Behaves as homozygous recessive lethal allele

Genotype AY AY does not survive

• Agouti

• yellow

• Mutant

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

Different modes of inheritance combined

– Results in many variants of modified ____

Example:

– Two heterozygotes mate

– Both autosomal recessive for ____

– Both _____

– Albinism inherited Mendelian style

– Blood types via three multiple alleles, I^A, I^B, and ii

• ratios

• albinism

• blood type AB

Phenotypic characters are influenced by _____

Gene interaction

– _____ influence a particular characteristic

– _____ of numerous gene products contributes to development of common phenotype

• many different genes and their products

• Several genes

• Cellular function

_______

– 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

• Epistasis

Epistasis and multiple gene interaction: _______

– 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

• Hereditary deafness

Epistasis has effect on one or more of four phenotypic categories

Recessive epistasis

– B allele: black pigment

– A allele: agouti phenotype

– aa genotype: all black

– bb genotype: _______, even if A or a alleles present

▪ Mouse is albino

– bb genotype ____ expression of A allele = _______

• no black pigment

• MASKS

• recessive epistasis

_______

– Dominant allele at one loci masks an allele at second loci

• Example: Summer squash fruit color

Dominant allele A = White fruit

• Regardless of _______

– Absence of A allele = Yellow fruit

▪ Genotypes aa, BB, Bb = yellow fruit

▪ Genotype bb = green

• Dominant epistasis

• second loci allele

______

– Screens number of individual mutations resulting in

same phenotype

– Can predict total number of genes determining a trait

_______

– All mutations present in any single gene

• Complementation analysis

• Complementation group

_____

– Expression of single gene has multiple phenotypic effects

Example: _____

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

• Pleiotropy

• Marfan syndrome

Pleiotropy Example: ______

– Autosomal disorder

– Toxic buildup of porphyrins in body

– Numerous phenotypic effects

▪ Abdominal pain

▪ Muscular weakness

▪ Fever

▪ Racing pulse

▪ Insomnia

▪ Vision issues

• Porphyria variegata

_______ Describes Genes on the X Chromosome

• X-Linkage

_______

– Genes present on X chromosome exhibit patterns of inheritance

– Different from autosomal genes

______

– Relatively inert genetically

– Male-specific genes on human Y chromosome

– Lacks copies of genes found on X chromosome

• X-linkage

• Y chromosome

______ 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

_____ locus present on X chromosome (X-linked)

• White eye mutation

• White

Color blindness: ______

– Red/green color blindness

– Mother passes to ____

– Mother passes to no ____

• X chromosome-linked

• all sons

• daughters

_____ inheritance

– Expression of specific phenotype is absolutely limited to one sex

______ inheritance

– Sex of individual influences expression of phenotype

– Not limited to one sex or the other

• Sex-limited

• Sex-influenced

_____ expression of trait

– Influenced by environment

– Influenced by genotype

Gene products function within cell in various ways

Organism exists in diverse environmental conditions

• Phenotypic

_______

– Percentage of expression of the mutant genotype in a population

______

– Range of expression of mutant phenotype

– Result of genetic background differences and/or environmental effects

• Penetrance

• Expressivity

______ in Drosophila

– Homozygous recessive mutant gene

– Phenotype ranges from presence of normal eyes to absence of one or both eyes

• Eyeless mutation

Genetic background: _____ effect

– Physical location of gene influences expression

– Translocation or inversion events modify expression

– Gene relocated to condensed or genetically inert chromosome (heterochromatin)

• 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)

• Position

Conditional Mutations

______ effects

– Evening primrose

▪ Red flowers at 23Celsius

▪ White flowers at 18Celsius

– Siamese cats and Himalayan rabbits

▪ Darker fur on cooler areas of body (tail, feet, ears)

▪ Enzymes lose catalytic function at higher

temperature

• Temperature

_______

– Viruses, bacteria, fungi, and _____

– Mutant allele expresses mutant phenotype at one temperature, wild-type phenotype at another

– Useful when studying phage (bacterial virus) mutants

• Temperature-sensitive mutations

• Drosophila

_____ mutations

– Prevent synthesis of nutrient molecules in microbes

– Auxotrophs (microbe)

– Phenotype expressed or not depending upon diet

______

– Loss of enzyme to metabolize amino acid phenylalanine

– Severe problems unless low-Phe diet

• Nutritional

• Phenylketonuria

_____

– Cannot metabolize galactose

_____

– Cannot metabolize lactose

• Galactosemia

• Lactose intolerance

Delayed onset of phenotypic expression

______

– Inherited autosomal recessive

– Lethal lipid-metabolism disease (hexosaminidase A)

– Baby normal for a few months, dies by age 3

______

– Inherited X-linked recessive

– Purine salvage enzyme defect (HPRTase)

– Normal for about 6 months

• Tay-Sachs disease

• Lesch–Nyhan syndrome

______dystrophy (DMD)

– X-linked recessive disorder

– Diagnosis at 3–5 years old, fatal by age 20

_____ 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

• Duchene muscular

• Huntington

_______

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

Example: _______

– Adult muscular dystrophy

– Autosomal dominant

– Increased severity and earlier onset with successive generations of inheritance

• Genetic anticipation

• Myotonic dystrophy (DM1)

Week 3 Learning Outcomes

• Discuss allelic variants from wild-type to mutated forms and their influence on phenotype from normal function to loss or gain of function.

• Practice solving the genotypic and phenotypic ratios of non-Mendelian traits that show incomplete dominance, codominance (MN blood group), and multiple alleles (ABO blood group).

• Compare the effect of dominant and recessive lethal genes on survival of offspring.

• Practice solving the offspring ratio from two gene pair combinations using the forked-line method.

• Demonstrate how phenotypes influenced by multiple genes as in epistasis modify the normal predicted dihybrid ratio of 9:3:3:1.

• Discuss the usefulness of complementation.

• Relate single gene with multiple phenotypic effects, pleiotropy.

• Practice solving the ratios produced by sex linked traits crosses.

• Recognize how alterations in phenotypic expression result from differences in genetic background and environmental factors (penetrance and expressivity).