Extensions of Mendelian Genetics Flashcards
Most genes have greater than 2 alleles in a population
Multiple Alleles
A single diploid can have up to _____ alleles in its genome.
2
Alleles arise through changes in the DNA sequence in a gene by________.
Mutation
T or F: Wild type occurs most often, but does not have to be dominant.
T
Calculating the number of possible genotypes in a population
-Based on number of alleles
n=number of alleles
Possible genotypes=n(n+1)/2
If there are 4 possible alleles, the number of genotypes in the population is?
4(4+1)/2 = 10
Hierarchy of dominance: Fly example
w^+ = wildtype (red)
w^e = eosin (reddish orange)
w = white allele
- Decreasing dominance
- fly eye color gene has more than 3 alleles
- has to do with gene expression and gene product function in depositing the color in the eyes.
Phenotype of heterozygote is intermediate to the homozygotes.
Incomplete Dominance
Molecular explanation of incomplete dominance
- Dependent upon gene dosage
- Homozygosity for functional allele causes 2 “doses” of a gene product
- Heterozygosity causes one “dose” of gene product
- Homozygosity for nonfunctional allele causes no dose of gene product
One dose of gene product supports life
- Threshold effect
- Trait classified as recessive autosomal
Haplosufficency
One dose of gene product is not enough to support life
Haploinsufficency
-Homozygous wild type= healthy
Haplosufficency/Haploinsufficency
-Homozygous mutant = unhealthy
Haplosufficency/Haploinsufficency
-Heterozygous = healthy
Haplosufficency
-Heterozygous = dead/severely sick
Haploinsufficency
Example of Haplosufficiency: Cystinosis
- is an autosomal recessive disorder
- caused by loss of fxn mutations in the CTNS gene
- Causes cells to store cystine
- patients have 100x more cystine than noncarrier controls
- carriers (patients) have 6-10x more cystine
Example of Haploinsufficiency: BRCA mutations
- autosomal dominant
- mutations cause increased risk for breast cancer
- gene products are involved in DNA repair
- Loss of fxn mutations increase risk for breast cancer
- heterozygosity causes increased risk of breast cancer
- individual that is homozygous for the mutation is embryonic lethal
Back up genes
Complementary genes
A gene that encodes a product required for life; when mutated, causes a lethal phenotype
-no back up gene
Essential gene
Presence results in death of individual
Lethal Allele
Need 2 copies of lethal allele to exhibit lethal phenotype
- most truly lethal in utero
examply: cystic fibrosis
Recessive lethal
Recessive lethal in C1 transport due to loss of fxn mutation
cystic fibrosis
both homozygotes for lethal allele and heterozygotes display the lethal phenotype
- typically from:
1) gain of fxn mutation
2) dominant negative mutation
ex. Huntingtons disease
Dominant lethal
Caused by a dominant negative mutation
Huntingtons disease
Loss of fxn mutation in mutant allele interferes with fxn of wild type allele
Dominant Negative Mutation
Mutate so it’s always on.
Onco gene
Heterozygote shows the phenotypes of both homozygotes simultaneously.
-ex: AB blood type
Codominance
Molecular explanation of Codominance
Equally strong, expressed gene products that don’t interfere with the cellular functions of each other.
Example of Codominance:
Coat color in some breeds of cattle
- RR= red hairs
- WW= white hairs
- RW= Roan (red and white hairs)
One gene is responsible for multiple phenotypes
ex. PKU (phenylketouria)
Pliotropy
Autosomal recessive; caused by loss of fxn mutation
-low IQ, seizures, light skin pigmentation (disease will change amino acid for melanin).
PKU (Phenylketouria)
When alleles are on the same chromosome, they tend to be inherited together unless separated by recombination.
Linked alleles
When 2 or more genes show strong linkage and one of the 2 genes has an allele that give a selective advantage, the other allele tends to be inherited with the advantagous allele
Genetic hitchhiking or Selective sweeps
ex. Crohn’s disease
Caused by delierious allele
-very close to other genes that give people an advantage.
Crohn’s disease
One trait is controlled by many gene pairs working together.
ex. eye color, skin color, height, personality, etc…
Polygenic trait
Form of gene interaction in which one gene interferes with the expression of another gene.
- polygenic phenomena
- one locus interferes with another locus
- one gene masks another gene
Epistasis
Gene doing the masking
epistatic gene
gene being masked
hypostatic gene
Alters the expression of a second gene.
ex. variable cystic fibrosis disease progression
Modifier gene
Homozygous recessive genotype at locus A masks phenotypic expression at locus B
- aa epistatic to BB, Bb, or bb.
- aaB_ and aabb have same phenotype
Recessive epistasis
Example of recessive epistasis:
Coat color in mice
- A_ agouti
- aa black
- C_ pigment made and deposited
- cc no pigment made and deposited
9: 3:4 phenotypic ratio
Presence of dominant allele at locus A masks phenotypic expression at locus B
- A_ is epistatic to BB, Bb, or bb
- A_B_ and A_bb will have same phenotypic outcome
Dominant epistasis
Example of dominant epistasis:
Summer squash color
- W white: pigment breaks down green pigments
- Y yellow: functioning by not phenotypically expressed
- y green
Wild type gene products are involved in complementary pathways.
ex. DNA repair enzymes, transcription factors, etc…
Synthetic lethal-negative epistasis
Mutation A- alive Mutation B- alive Mutation in both A and B- dead *A is masking mutation in b B is masking mutation in a
Synthetic Lethal-negative epistasis
Not all individuals with a particular genotype display the expected phenotype
Gene expression and the enviornment:
-Genetics cannot be separated from the enviornment
Age, internal signals, genetic factors, etc..
Internal enviornment
Temperature, chemicals, nurture, etc..
External enviornment
Things the environment has an effect on:
- Lung capacity
- Skin color
- IQ
- Metabolism
Enzymes lose catalytic function at higher temperature:
ex. siamese cats and Himalayan rabbits have darker fur on cooler areas of body (tail, nose, ears)
Example of environmental effects: temp sensitive genes
Variations in phenotype
- Norm of reaction
- Penetrance
- Expressivity
Range of potential phenotypes for a particular genotype
Norm of reaction
The percentage of individuals with a particular genotype of interest who show the expected phenotype
Penetrance
Degree to which a phenotype is expressed; severity of the phenotype
Expressivity
Variations in phenotype due to:
Enviornment, epigenetics, modifier genes
Physical location of a gene that can influence expression; genetic background of the individual
*nearby CpG island?
Position effect (Epigenetics)
Can suppress or enhance phenotypic expression
modifier genes
Neural growth is over activated
Incomplete penetrance (50-80% penetrance)
ex. Neurofibromatosis: human disease caused by dominant allele, not caused by gene dosage
- expressivity ranges from brown spotting to tumor like growths
Variable expressivity
Ex. Osteogenesis imperfecta (brittle bone disease)
- autosomal dominant
- 100% penetrance
- may have one or up to three of the following traits: blueness in sclerae of eyes, fragile bones, deafness
DNA found in mitochondria and chloroplasts:
- Circular
- mtDNA –encode proteins involved in energy
- CpDNA (chloroplast DNA) encode proteins involved in energy production
Extranuclear Genes
Mitochondria in egg cytoplasm are inherited in that offspring
Extranuclear inheritnace—typically maternal inheritance
Phenotype of offspring is determined by nuclear genotype of the mother
-mRNA and proteins are made in oocyte and deposited there before fertilization.
Maternal Effect
Example of Maternal effect
Snail Shell coiling:
- genes expressed in egg influence genotype during development
- Look at mother’s genotype, not phenotype!
In a plant species, two blue plants are mated and produce 303 blue plants and 98 white plants. These observations can best be explained by:
a. incomplete dominance
b. complete dominance
c. codominance
d. haploinsufficiency
b. complete dominance
A cross between two short-tailed mice results in offspring in the ratio of 67 short-tailed and 34 long-tailed. The best explaination for this result is that:
a. two alleles are codominant
b. there is a lethal allele
c. there are at least three alleles
d. there is simple dominance between two alleles
b. there is a lethal allele
