M1 L4: Modification of Mendelian Ratios Flashcards
how do we get modifications of mendelian ratios?
gene/gene interaction, gene/enviro interaction
Where do dominance relationships come from?
Interactions between alleles, threshold amt of activity required to exhibit phenotype
what are haplosufficiency and haploinsufficiency?
haplosufficiency: one WT allele is enough to exhibit the WT phenotype
haploinsufficiency: one WT allele is not enough to exhibit the WT phenotype
What are the two main types of mutations in terms of function?
1) loss of function
2) gain of function
2 types of loss of function mutations? Characteristics?
1) null/apomorphic: complete loss of function (can be from pt, nonsense, frameshift, deletions)
2) leaky/hypomorphic: decreased function (usually from pt)
typically recessive
2 types of gain of function mutations? Characteristics?
1) hypermorphic: same function but increased expression (can be pt but usually duplications)
2) neomorphic: new function acquired (usually pt)
typically dominant
what are dom neg mutations? what’s an example?
when a loss of function mutation is dominant
ex) osteogenesis imperfecta is bone deformities caused by collagen mutation. collagen is usually 2 A1 proteins, 1 A2 protein. Hets have 3:1 broken:normal A1 proteins –> 3:1 broken:normal collagen fibers
What are the types of dominance? Phenotype ratios of F1 (het) crosses?
1) complete dominance: one trait fully dominant over the other, no mixing of phenotypes 3:1
2) incomplete dominance: some offspring are intermediates of parents 1:2:1
3) co-dominance: some offspring are mix of parents (show both distinct parental phenotypes at one time) 1:2:1
Example of a gene with multiple alleles?
Gene for ABO blood cell antigens has IA, IB, i
IA, IB co-dom, i recessive to both
What is the bombay phenotype? What type of interaction is it?
Person cannot make A or B antigens for blood, will test as type O but cannot receive O (“H substance” = foreign)
mutation in FUT1 gene prevents production of “H substance” –> individual can’t turn “H substance” into A/B antigens
Example of gene/gene interaction (epistasis)
what is epistasis? examples?
gene/gene interaction
Bombay phenotype and labrador coloring
example of allelic series (alleles have hierarchy relationship)
rabbit fur color
C (normal) > Cch (chinchilla) = Ch (himalayan) > c (albino)
Cch Ch results in intermediate between co and incomplete dom (lighter chinchilla with himalayan markings)
What are lethal alleles? Usually recessive or dominant? Why?
Mutations that result in death if the individual is homozygous for them
usually recessive
If they were dominant, those individuals would die and not reproduce
what are the 2 types of lethal alleles in plants?
embryo lethal: kills fertilized embryo (occurs in 3:1 ratio if parents were hets)
gametophyte lethal: egg is inviable after meiosis (occurs in 1:1 ratio bc of segregation)
What’s an example of a lethal allele in animals? Typical phenotype ratio in animals?
AY allele in mice
AY allele is deletion of RALY gene and agouti promotor –> agouti gene controlled by strong RALY promoter –> produce more yellow pigment
RALY is necessary for life and haplosufficient, mice can live with 1 RALY gene (AY het) but not 0 RALY genes (AY homo)
usually 2:1 het:homo non lethal bc homo lethal individuals are not observed (dead)
Lethal allele example in humans? Why is it unique? Why can’t NS weed it out?
Huntington’s (causes neuromuscular degeneration)
Unique bc it’s caused by a dominant lethal allele
NS can’t weed it out bc symptoms usually appear after repro age, individual already reproduces before dying
What is sex linkage? What’s an example?
M/F have dif patterns of inheritance
allele for white-eyed flies is on X chromosome
heterogametic sex only needs one copy of recessive allele to have recessive phenotype (usually male)
homogametic sex needs two copies of recessive allele to have recessive phenotype (usually female)
what are heterogametic and homogametic sexes
hetergametic sex: will show rec phenotype even if they only have 1 copy of rec allele
homogametic: will show rec phenotype only if they have 2 recessive alleles
what does hemizygous mean?
individual only has 1 copy of the gene (males are hemizygous for X chromosome, they only have 1)
What are the 4 types of variable phenotypes
1) sex limited traits
2) sex influenced traits
3) variable penetrance
4) variable expressivity
What are sex limited traits? Example?
genotype can be present in both sexes, phenotype limited to one sex (usually due to m/f hormones)
male canary songs: male hormones change throat muscles and neurons to produce vocalizations that females do not
(also breast development/milk in female mammals, horn growth in certain types of male sheep/cows)
what are sex influenced traits? example?
phenotype can occur in both sexes but w/ different inheritance patterns
(goat beards and male pattern baldness; different alleles are dominant in m/f; one allele can cause a male to be bald whereas female would need two)
what is incomplete penetrance? example?
individuals might have the same genotype, but only some express the phenotype
polydactyly is caused by a single dominant allele but not everyone with a dominant allele has polydactyly (nonpenetrant individuals)
what is variable expressivity? example?
individuals with the same genotype express the phenotype but to different degrees
waardenburg syndrome (autosomal dominant) has 4 phenotypes; affected individuals can express any combo of them
what are the 3 ways incomplete penetrance and variable expressivity arise?
1) enviro can affect if/how much the trait is expressed
2) other genes can affect if/how much the trait is expressed (pleiotropic genes)
3) both genes and enviro can affect if/how trait is expressed
gene environment interactions vs GxE (gene by environment interactions)? examples?
Gene enviro: environment affects gene expression
PKU (Phenylketonuria): can’t break down phenylalanine, intellectual disability and/or microcephaly if you eat it, no abnormal expression if enviro controlled and phenylalanine not ingested
GxE: do the genes have same or dif relationship to enviro? (same = no GxE, dif = yes GxE)
what are pleiotropic genes? example?
genes that affect multiple traits
1) agouti gene (AY allele affects color and viability)
2) genes that result in antibiotic resistance can decrease viability in other environments
3) sickle cell allele gives malaria resistance but can cause other complications
How is labrador coloring determined? What type of interaction is it?
B black dom over b brown, expression of Bb locus is contingent on genotype at Ee locus (ee –> yellow, Ee/EE –> black/brown)
who proposed that gene expression in pathways?
Archibald Garrod
What did the Beadle and Tatum experiment do and show? How do you determine where the mutated enzyme acts in a pathway?
Mutated different genes in each cell, placed all cells in complete media (should all grow), test each mutant in media w/ 1 supplement (supplement where they grow corresponds to their auxotrophy)
Showed single mutations cause defects in single enzymes
Tell where the pathway was disrupted w/ genetic dissection, place each mutant in each type of supplemented medium, see what supplement is necessary for pathway completion and what intermediates accumulate
What’s a prototroph
organism that can grow on minimal media (glucose and nitrogen source)
what’s an auxotroph/auxotrophy?
auxotroph: organism unable to complete pathway, req supplementation
auxotrophy: inability to synthesize a compound in a pathway
purpose of complementation analysis? how to perform? what do results mean?
purpose: see if mutants have same phenotype bc of mutations in dif (heterogeneity) or same genes
how: cross mutants with same phenotype
result interpretation:
1) offspring has same mutant phenotype as both parents –> mutation in same gene (same complementation group; no complementation) (offspring must have gotten 2 rec alleles)
2) offspring has WT phenotype –> mutations are in dif genes (dif complementation groups; yes complementation) (offspring het for both genes)
what’s heterogeneity
mutations in dif genes resulting in same phenotype
How to tell if mutations are in the same complementation group
if they DO NOT complement each other (-) sign on chart, they are in the same group
how to tell min. # of genes from complementation analysis
different complementation groups = min # of genes
explain threshold model of dominance
min. (threshold) amt protein activity req for trait to be expressed. If one copy of an allele is enough to reach the threshold, that allele is dominant
