Lecture 3: Relating Genotype to Phenotype
Mutant allele
- allele whose frequency is less than 1%
Wild-type
- by convention—any allele whose frequency is more than 1%
Expressivity
- degree or intensity with which a particular genotype is expressed in a phenotype Expressivity can be variable or unvarying. retinoblastoma again, 1 or 2 eyes with effect.
Polymorphic
- gene with more than one wild-type allele
Monomorphic
- gene with only one wild-type allele (fairly common in lab genetics- why?)
Penetrance
- percentage of a population with a particular genotype that show the expected phenotype -Penetrance can be complete (100%) or incomplete (e.g., retinoblastoma penetrance is 75%-only 75% of homozygous recessives show disease). intraocular cancer of childhood, 1st cancer to be defined as a genetic disease.
Pleiotropy
- single gene determines more than one distinct and seemingly unrelated characteristic.
Multifactorial inheritance- phenotype arises from the
--interaction of one or more genes with each other --interaction of one or more genes with the environment.
Do variations in dominance relations negate Mendel's law of segregation?
-Dominance relations affect phenotype and have no bearing on the segregation of alleles. -Alleles still segregate (separate) in gametes. -Gene products control expression of phenotypes differently. -Mendel's law of segregation still applies. Interpretation of phenotype/genotype relation is more complex.
Incomplete dominance (mixing paints)
-F1 hybrids that differ from both parents express an intermediate phenotype; Neither allele is dominant or recessive to the other. -Phenotypic ratios are the same as genotypic ratios.
Codominance (mixing water and oil)
-F1hybrids express phenotype of both parents equally. -Phenotypic ratios are same as genotypic ratios.
Sickle Cell anemia
-Multiple alleles -Normal wild-type is HbbA (Hemoglobin b-globin chain, A allele). -More than 400 mutant alleles identified so far -HbbS allele specifies abnormal peptide causing sickling among red blood cells
Single-gene inheritance exceptions to Mendel
-Pairs of alleles show deviations from complete dominance and recessiveness -Different forms of the gene are not limited to two alleles -Where one gene may determine more than one trait
complementary gene action
-Two genes work together to produce a phenotype. -9:7 ratio is a phenotypic signature where dominant alleles of two genes act together to produce a trait while the other three genotypic classes do not. (the other three classes are homozygous recessive for one or the other, or for both genes)
epistasis
-an allele at one locus hides the alleles at another gene. - can be recessive or dominant -9:3:4 is a telltale ratio of recessive epistasis.
3 allele example (ABO blood group)
6 possible ABO genotypes: IAIA, IBIB, IAIB, IAi, IBi, or ii -Dominance or recessiveness is always relative to a second allele. -IA is completely dominant to i but codominant to IB. -6 genotypes generate 4 phenotypes.
mutant
<1%
wild type
>1%
Complementation testing can determine if mutations arise from the same or different genes- for heterogeneous traits
A way to test if identical recessive phenotypes are result of the same mutatio-It is not always possible to determine which of many genes is mutated in an individual with a heterogeneous mutant phenotype.
Blood types
A/ B- corresponds to sugars that the blood matches with. (A can't have B-sugars, B can't have A sugars, O doesn't have any sugars so will react to A, or B, or AB) AA and BB people will have an AB child. codominance.
Which can receive blood from any?
AB
example of multiple alleles and multifactorial traits
Agouti gene has multiple alleles -Wild-type A allele specifies bands of yellow and black. -AY gets rid of black and produces solid yellow. a gets rid of yellow band and produces solid black or br. -at specifies br or bl pigment on the back and yellow on the stomach -Dominance series is AY > A > at > a. -AY is however, recessive to all others for lethality. -AYAY die. All other AY - combinations survive. Gene 2 - black or brown -Second gene specifies whether dark hair from gene one is black or brown. b is recessive and generates brown. B is dominant and generates black. AY alleles completely eliminates dark hair, and thus acts in a dominant epistatic manner to the B gene. A_B_ produces wild-type agouti with black and yellow hairs. A_bb generates cinnamon (agouti hairs with brown and yellow) aabb is all brown. atatbb is brown on the back and yellow on the stomach. AYaBb X AYaBb would produce a ratio of 8 yellow (AY_,__), 3 black (aa, B_), 1 brown (aa, bb). The AYAY class of 4 would be missing because of lethality. -Gene 3 is albino or pigmented cc= all white Cc or CC is any of the other colors
epistasis in labs
Coat color can be black, chocolate brown, or golden yellow -B allele is dominant and determines black. -b allele is recessive and determines brown if homozygous. -E allele at second gene has no affect on coat color. -e allele is recessive and if homozygous hides effects of black or brown alleles. -e allele is epistatic to B locus.
where do new alleles come from?
Multiple alleles arise spontaneously in nature due to chance alterations in genetic material - mutations.
two genes can interact to form one trait
Novel phenotypes can emerge from the combination of alleles of two genes.
Which can give blood to any?
O
two gene vs one gene testing hypothesis
One gene= 3:1 in T2 generation two gene= 9:3:3:1 i.e. 9:3:4
Dominant epistasis
Presence of dominant allele at second gene hides effects of alleles at a gene. 12:3:1 and 13:3 are telltale ratios for dominance epistasis.
Pleiotropy with HbbS
Sickling Resistance to malaria Recessive lethality Different dominance relations for different traits
Some alleles may cause lethality.
Type of pleiotropy where alleles produce a visible phenotype and affect viability Alleles that affect viability often produce deviations from a 1:2:1 genoptypic and 3:1 phenotypic ratio predicted by Mendel's Laws.
heterogeneous trait and alleles
With heterogeneous trait, mutant alleles at any one of two or more genes are sufficient to elicit a phenotype.
pleiotropy in Agouti mice
a. Inbred agouti X yellow yields 1:1 agouti:yellow Yellow must be AYA and AY is dominant to A B. Yellow x yellow mice do not breed true. AY is a recessive lethal. AYAY die in utero and do not show up as progeny, which gives you a 2:1 phenotypic and genotypic ratio
enviornment
affect the phenotypic expression of a genotype. "conditional phenotype" -Temperature is a common element of the environment that affects phenotype. --Coat color in Siamese cats is darker in its extremities (legs, tails, ears, etc.) because of a mutation that renders an enzyme involved in melanin synthesis temperature sensitive. --Conditional lethals- permissive condition. shibire gene in Drosophila melanogaster is lethal at temperatures above 29oC.
continuous traits, quantitative. (usually polygenic)
are determined by segregating alleles of many genes interacting with one another and the environment. -The more genes that contribute to a trait, the greater the number of possible phenotypic classes and the greater the similarity to continuous variation
ABO epistasis
bombay phenotype homozygous recessive at H (hh) H substance is required to put A and B sugars on cell surface. hh means that it cannot do that, so it glutinates the sugars. ABO can only receive bloom from ABO
Complementation tests
can reveal whether a particular phenotype arises from mutations in the same or separate genes.
Phenocopy
change in phenotype arising from environmental agents that mimics the effect of a mutation at a gene genetic deafness vs. high noise induced mutant nutrient uptake vs. poor nutrition
Test cross for epistasis in yellow lab
cross pure breeding brown lab with brown lab (so bbEE not bbEe because a fourth of the progeny would be yellow labs)
How can you tell the genotype of type A?
cross with an O type. Do a test cross.
Mutation rate varies from 1 in 10,000 to 1 in 1,000,000 per gamete per generation.
depends on number of nucleotides (longer genes, more nucleotides, more room for error), environmental factors, transposons
Modifier genes
genes are under the same rules as any gene but their phenotypic effect is often so minor that they are very difficult to follow in crosses, etc.
Heterogeneous traits
have multiple genes underlying their expression- mutations in 2 or more genes can give the same phenotype
complementation testing
if you have an unknown mutant, and you cross it to a known mutant- - if they complement, it is at a different gene -if they do not, then it is a new mutation at that gene
Complementary gene action
is when dominant alleles of two or more genes are required to generate a trait.
Epistasis
is when the action of an allele at one gene hides traits normally caused by alleles at another gene.Can be dom. or rec.
polymorphic
more than one wild type allele in a population
Momomorphic
only one allele in a population
example of complementary gene action
pea plants: Purple flowers are any combination where AABB has at least one dominant allele for each gene. If A or B does not (i.e. aa or bb), then the result is a white flower
how to establish dominance relationships between all alleles?
perform crosses between pure breeding lines
OAC1 tyrosinase in siamese cats
protein gets denatured at warmer temperatures, so darker hair color in extremities
How you cross pea plants
remove stamen from one plant. Use stamen from another plant to transfer
Allele frequency
the percentage of the total number of gene copies represented by one allele.
complementation test showing they did not
two deaf people have a deaf child ( aaBB*aaBB=aaBB)
complementation test- showing they did complement
two deaf people have a non deaf child (so likely aaBB*AAbb= AaBb)
consanguineous
when an individual comes from the same genetic background as another individual
heterogeneus
when there are two or more genes that complement to form a phenotype
can a gene have more than two alleles?
yes, there can be more than two in a population, but individuals will typically only have two
