Genetics

Chapter 4, Part 1

GENE INTERACTIONS

Genes Interact!

• So far we have looked at dominant/recessive, but the real story is more complicated…

• EPISTASIS: How genes interact to express phenotypes

• There may be more than two alleles for a given locus within a population How many alleles per gene are present in a diploid individual?

• Dominance of one allele over another may not be complete

• Two or more genes may affect a single trait• The expression of a trait may

depend on the interaction of more than one gene and/or the interaction of genes with nongenic factors

Gene Interaction

• The phrase gene interactions refers to the ways genes collaborate or interact to influence a phenotype

• There are several important types of interactions

4.1 Interactions between Alleles Produce Dominance Relationships

The Molecular Basis of Dominance

• The terms dominant and recessive have a phenotypic basis

• However, the dominance of one allele over another is determined by the protein product of that allele

• The overall phenotype is the consequence of the activities of the protein products of the alleles of the gene

http://hereausclasses.weebly.com

Mutations of haplosufficient genes are recessive

Haplosufficient: a wild-type allele that supports wild type function in a heterozygous organisms (dominant wild-type allele).

Haploinsufficiency: when one copy of an allele is not enough

The mutant allele is dominant to the wild type allele because individuals heterozygous or homozygous for the mutant allele are both mutant in phenotype

Dominance is the interaction of Genes at the Same Locus

• Genes at the same locus – two versions of the same gene; each version of the same gene is defined as allele.

• Dominance can be complete or incomplete• Incomplete: heterozygous falls in the

range between two homozygous

• Not always a perfect ‘pink’

• Codominance: offspring express the phenotype of both parents equally• Phenotypic ratios are the same as

genotypic ratios (blood type)

Incomplete Dominance

• Often the dominance of one allele over the other is not complete,• allele designations such as A1, A2 or

B1, B2 are used instead of A, a or B, b

• Incomplete dominance, or partial dominance • heterozygous individuals display

intermediate phenotypes between either homozygous type

• Typically the heterozygote is more similar to one of the homozygous types than the other

Incomplete Dominance: Time to Flowering

Codominance

• Codominance leads to heterozygotes with a different phenotype than that of either homozygote

• In this case, there is detectable expression of both alleles in the heterozygotes

• More than one pattern of dominance may exist between different alleles of a gene, e.g. ABO blood type

Dominance Relationships of ABO Alleles

• The ABO blood type has 4 different types, resulting from different combinations of 3 alleles

• The alleles are: IA, IB and i; the IA and IB alleles are completely dominant over the i allele, but they are codominant with each other

• The A blood type involves the presence of one antigen on the blood cell surfaces; type B the presence of a different antigen

• Type AB people have both antigens and type O people have neither

Blood Types and Genotypes

• Type A: IAIA or IAi

• Type B: IBIB or IBi

• Type AB: IBIA

• Type O: ii

Antiserum

Allelic Series

• In populations the number of alleles is theoretically unlimited and some genes have many

• A locus with more than two alleles is said to have multiple alleles

• An order of dominance among the alleles may form a sequential series referred to as an allelic series

www.mun.ca

The C-Gene System for Mammalian Coat Color

• Many genes are required to produce and distribute pigment to the hair follicles or skin cells, where they give rise to skin or coat color

• The C gene is responsible for coat color in mammals like cats, rabbits and mice, etc.

• It produces an enzyme active in the production of melanin

• There are dozens of alleles of the gene, but four that form an allelic series

cnx.org

The Allelic Series of the C Gene

• The wild type allele, C, produces a functional enzyme and full coat color

• cch produces a “dilute” phenotype called chinchilla

• ch produces a phenotype called Himalayan with little pigment on the body but full color on the extremities

• c is a fully recessive null allele and produces an albino phenotype

Therefore, C is dominant over cch, ch, and c

Let’s test for dominance….

How do the rest interact with each other?….

Therefore, C > cch > ch > cChinchilla is partially dominant over Himalayan

Dominance relationship: C>cch>ch>c

The Allelic Series of the C Gene

The Molecular Basis of the C-Gene Allelic Series

• The C allele produces a tyrosinase enzyme that is 100% active, whereas that of the cch allele is less than 20% active

• The ch allele enzyme is temperature-sensitive; functional at lower temperatures (like the paws, ears and tail) and non-functional at higher temperatures (the trunk)

• The c allele produces no functional enzyme

Lethal Alleles

• Some single-gene mutations are so detrimental that they cause death in the organism

• These are caused by lethal mutations, which are inherited as recessive alleles (only the homozygotes die)

• Lethal alleles can be detected as distortions in segregation ratios caused by one or more missing classes of progeny

Molecular Basis of the AY Lethality

• The AY mutation is caused by a deletion that affects two genes, Agouti and Raly

• Raly produces a protein essential for mouse development; the deletion connects the Raly promoter to the Agouti gene

• In heterozygotes, the Raly promoter drives a high level of Agouti gene transcription, resulting in an excess of yellow pigment is produced (displaces black pigment), whereas homozygotes die due to lack of the Raly protein

LETHAL ALLELES MAY ALTER PHENOTYPIC RATIOS

• A lethal allele: causes death at an early stage of development, and so some genotypes may not appear among the progeny

• Alleles that affect viability often produce deviations from a 1:2:1 genoptypic and 3:1 phenotypic ratio predicted by Mendel’s Laws.

PLEIOTROPIC GENES

• Pleiotropy is the alteration of multiple distinct traits of an organism by a mutation in a single gene.

• Two main mechanisms:• Direct action of a mutant protein

• Ex. Mendel’s white flowers had mutated anthocyanin, which also produces gray seed coats & lack of color at leaf axils

• Secondary result of a cascade of problems stemming from the mutation

• Ex. Sickle cell disease

SICKLE CELL DISEASE (SCD)

• SCD is an autosomal recessive condition caused by mutation of the β-globin gene that, in turn, affects the structure and function of hemoglobin (the main oxygen-carrying molecule in red blood cells)

• Mutation in β-globin cause the red blood cells to take on a sickle shape

• Causes a wide range of physical complications

SICKLE-CELL SYNDROME

• Multiple alleles for β-globin gene of hemoglobin• Normal wild-type is HbbA

• More than 400 mutant alleles identified so far• HbbS allele specifies abnormal peptide causing sickling

among red blood cells

• Pleitropy• HbbS affects more than one trait

• Sickling

• Resistance to malaria

• Numerous disease symptoms

• Recessive lethality

• Different dominance relations

Hemoglobin:iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates-Beta subunit in blue-Alpha subunit in red

PLEITROPY OF SICKLE-CELL SYNDROME

COPYRIGHT © THE MCGRAW-HILL COMPANIES, INC. PERMISSION REQUIRED TO REPRODUCE OR DISPLAY

Malaria: parasitic protozoan that attacks red blood cells, transmitted by mosquitoes

Sex-Limited Traits

• The sex of an organism can influence gene expression

• Sex-limited gene expression is a pattern of expression limited to one sex or the other

• The traits involved are called sex-limited traits; both sexes carry the genes for such traits, but they are expressed in just one sex

Sex-Limited Traits: Examples

• Mammalian breast and ability to produce milk are female-specific traits

• Horn development is limited to males in some sheep, cows and other hoofed animals

• Behavioral traits, especially related to mating are strongly influenced by sex

• Sex hormones differentially influence expression of genes related to these and other sex-limited traits

Sex-Influenced Traits; Baldness

• Sex-influenced traits are those in which the phenotype corresponding to a particular genotype differs depending on the sex of the organism

• Male pattern baldness is an example:• In males and females, BB individuals have full hair• bb individuals experience hair loss but males have much more hair loss due to

the effect of male hormones• Bb males experience hair loss just like bb males, while females have full hair

Male hair loss: Bb or bb Female hair loss: bb

Sex-Influenced Traits• Bearded vs. beardless

Dominant Lethal Alleles & Delayed Age of Onset

• Dominant lethal alleles can sidestep natural selection if they have a delayed age of onset

• The abnormalities they produce are not expressed until after the affected individual has reproduced

• A prominent example is Huntington Disease (HD), a fatal neurodegenerative disorder which does not usually show symptoms until the late 30s or 40s• Neurodegenerative disorder causing cognitive

• decline & psychiatric issues

• Causes writhing movements call chorea,

• used to be called Huntington’s Chorea

http://learn.genetics.utah.edu

• So far, phenotypes can be distinguished with 100% certainty• All individuals with certain genotype express the

expected phenotype

• But… some individuals do not express the genotype

• Penetrance: percentage of individuals having a particular genotype that express the expected phenotype

Penetrance and Expressivity Describe How Genes Are Expressed as Phenotype

• Why not to express the corresponding genotype?• Influence of the environment: same genotype may

result in range of phenotypes.

• Influence of other interacting genes: more on this through the following lectures

Penetrance and Expressivity Describe How Genes Are Expressed as Phenotype

• Penetrance: percentage of individuals having a particular genotype that express the expected phenotype

• Measures how often the phenotype occurs

• Expressivity: the degree to which a character is expressed

• Measures the intensity of the phenotype

• Both examine how gene expression is affected by environment and genetic background.

Penetrance and Expressivity Describe How Genes Are Expressed as Phenotype

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Incomplete Penetrance

• An organism is penetrant for a trait when the phenotype is consistent with the genotype

• An organism which does not produce the phenotype generally associated with the genotype is nonpenetrant

• Traits for which nonpenetrant individuals routinely occur are said to display incomplete penetrance

www.cancer.gov

Incomplete Penetrance: Polydactyly

• Polydactyly is an autosomal dominant condition, in which affected individuals have more than 5 fingers and toes

• The dominant allele is nonpenetrant in about 25 – 30% of individuals carrying it

Polydactyly

Variable Expressivity

• In variable expressivity individuals who carry the alleles for a trait show a phenotype but to a varying degree of severity

• Waardenburg syndrome has four principle features• Premature graying, hearing loss, white

forelock, different colored eyes

• Each family member with Waardenburg syndrome has the same genotype but shows a different combination of symptoms

Variable Expressivity: Waardenburg syndrome

Gene-Environment Interactions

• Genes alone are not responsible for all the variation seen between organisms

• Gene-environment interaction is the result of the influence of the environment on the expression of genes and on the phenotype of the organism

• Ex: Drug use can change gene expression!

http://www.niehs.nih.gov

National Institute of Environmental Health Sciences-carcinogens, fetal alcohol syndrome, Autism risks and the environment, climate change & human health, respiratory disease and pollution, etc.

Environmental Modification to Prevent Hereditary Disease

• The human autosomal recessive condition, PKU (phenylketonuria) is caused by the absence of an enzyme involved in phenylalanine breakdown

• Infants with PKU are normal at birth, but over time, the inability to break down phenylalanine is toxic to developing neurons

• PKU is one of the hereditary disorders infants are routinely screened for

Preventing Symptoms of PKU

• The key to preventing PKU is restricting phenylalanine in the diet of infants found to have PKU

• Thousands of people with PKU are living normal lives due to the simple dietary modification that prevents the expression of the PKU phenotype

depts.washington.eduwww.pku.com

Questions?

Just allele uneven