M1 L4: Modification of Mendelian Ratios

Question 1

how do we get modifications of mendelian ratios?

Answer 1

gene/gene interaction, gene/enviro interaction

Question 2

Where do dominance relationships come from?

Answer 2

Interactions between alleles, threshold amt of activity required to exhibit phenotype

Question 3

what are haplosufficiency and haploinsufficiency?

Answer 3

haplosufficiency: one WT allele is enough to exhibit the WT phenotype

haploinsufficiency: one WT allele is not enough to exhibit the WT phenotype

Question 4

What are the two main types of mutations in terms of function?

Answer 4

1) loss of function

2) gain of function

Question 5

2 types of loss of function mutations? Characteristics?

Answer 5

1) null/apomorphic: complete loss of function (can be from pt, nonsense, frameshift, deletions)

2) leaky/hypomorphic: decreased function (usually from pt)

typically recessive

Question 6

2 types of gain of function mutations? Characteristics?

Answer 6

1) hypermorphic: same function but increased expression (can be pt but usually duplications)

2) neomorphic: new function acquired (usually pt)

typically dominant

Question 7

what are dom neg mutations? what’s an example?

Answer 7

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

Question 8

What are the types of dominance? Phenotype ratios of F1 (het) crosses?

Answer 8

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

Question 9

Example of a gene with multiple alleles?

Answer 9

Gene for ABO blood cell antigens has IA, IB, i

IA, IB co-dom, i recessive to both

Question 10

What is the bombay phenotype? What type of interaction is it?

Answer 10

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)

Question 11

what is epistasis? examples?

Answer 11

gene/gene interaction

Bombay phenotype and labrador coloring

Question 12

example of allelic series (alleles have hierarchy relationship)

Answer 12

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)

Question 13

What are lethal alleles? Usually recessive or dominant? Why?

Answer 13

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

Question 14

what are the 2 types of lethal alleles in plants?

Answer 14

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)

Question 15

What’s an example of a lethal allele in animals? Typical phenotype ratio in animals?

Answer 15

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)

Question 16

Lethal allele example in humans? Why is it unique? Why can’t NS weed it out?

Answer 16

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

Question 17

What is sex linkage? What’s an example?

Answer 17

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)

Question 18

what are heterogametic and homogametic sexes

Answer 18

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

Question 19

what does hemizygous mean?

Answer 19

individual only has 1 copy of the gene (males are hemizygous for X chromosome, they only have 1)

Question 20

What are the 4 types of variable phenotypes

Answer 20

1) sex limited traits
2) sex influenced traits
3) variable penetrance
4) variable expressivity

Question 21

What are sex limited traits? Example?

Answer 21

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)

Question 22

what are sex influenced traits? example?

Answer 22

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)

Question 23

what is incomplete penetrance? example?

Answer 23

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)

Question 24

what is variable expressivity? example?

Answer 24

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

Question 25

what are the 3 ways incomplete penetrance and variable expressivity arise?

Answer 25

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

Question 26

gene environment interactions vs GxE (gene by environment interactions)? examples?

Answer 26

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)

Question 27

what are pleiotropic genes? example?

Answer 27

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

Question 28

How is labrador coloring determined? What type of interaction is it?

Answer 28

B black dom over b brown, expression of Bb locus is contingent on genotype at Ee locus (ee –> yellow, Ee/EE –> black/brown)

Question 29

who proposed that gene expression in pathways?

Answer 29

Archibald Garrod

Question 30

What did the Beadle and Tatum experiment do and show? How do you determine where the mutated enzyme acts in a pathway?

Answer 30

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

Question 31

What’s a prototroph

Answer 31

organism that can grow on minimal media (glucose and nitrogen source)

Question 32

what’s an auxotroph/auxotrophy?

Answer 32

auxotroph: organism unable to complete pathway, req supplementation

auxotrophy: inability to synthesize a compound in a pathway

Question 33

purpose of complementation analysis? how to perform? what do results mean?

Answer 33

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)

Question 34

what’s heterogeneity

Answer 34

mutations in dif genes resulting in same phenotype

Question 35

How to tell if mutations are in the same complementation group

Answer 35

if they DO NOT complement each other (-) sign on chart, they are in the same group

Question 36

how to tell min. # of genes from complementation analysis

Answer 36

different complementation groups = min # of genes

Question 37

explain threshold model of dominance

Answer 37

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