Coat Color Genetics

Question 1

melanocytes

Answer 1

pigment producing cells in mammals

Question 2

what are melanocytes derived from

Answer 2

melanoblasts (neural crest cells)

Question 3

how do genes affect melanocyte distribution in the body

Answer 3

controls the number, migration, and survival of melanocytes

Question 4

where is the first area that white spots will appear

Answer 4

periphery
- farthest distance from the neural crest

Question 5

what are pigments derived from

Answer 5

tyrosine

Question 6

how do pigments get distributed to hair

Answer 6

pigments get deposited in granules (melanosomes) that get distributed along the hair shaft

Question 7

what are the two main pigments

Answer 7

pheomelanin
eumelanin

Question 8

pheomelanin

Answer 8

yellow, red, white pigments

Question 9

eumelanin

Answer 9

black pigment

Question 10

what causes banding pattern of hair

Answer 10

timing of pigment distribution during hair growth

banding:
black (eu) –> yellow (pheo) –> black (eu)

Question 11

what are the two main genetic controllers of pigment

Answer 11

MC1R
ASIP

Question 12

MC1R

Answer 12

melanocortin receptor-1

G protein coupled receptor

1. MSH binds MC1R
2. MC1R triggers increase in cAMP
3. signals eumelanin production

Question 13

ASIP

Answer 13

agouti signaling protein

1. ASIP binds to MC1R and blocks MSH binding
2. decreases cAMP
3. signals pheomelanin production

Question 14

what are the two ASIP transcription promoters

Answer 14

ventral promoter
hair cycle promoter

Question 15

ventral promoter

Answer 15

if transcription of ASIP begins at the ventral promoter –> pheomelanin will expressed on ventrum

medium expression: pheomelanin on ventral muzzle, distal limbs, and chest

high expression: pheomelanin everywhere except dorsum

Question 16

hair cycle promoter

Answer 16

if transcription of ASIP begins at the HCP –> pheomelanin will be expressed in a banding pattern across the body

medium expression: banded, dark

high expression: banded, light

Question 17

what are the two ways of getting yellow coat color

Answer 17

1. MC1R loss of function
2. ASIP gain of function

Question 18

MC1R loss of function

Answer 18

yellow

common but recessive

1. decreased expression of MC1R
2. no cAMP increase
3. pheomelanin

Question 19

ASIP gain of function

Answer 19

yellow

less common but dominant
(requires increased expression from both promoters)

1. overexpession of ASIP over entire body
2. blocks MSH at all MC1R
3. pheomelanin

Question 20

what are the 3 ways of getting black coat color

Answer 20

1. ASIP loss of function
2. MC1R gain of function
3. K locus

Question 21

ASIP loss of function

Answer 21

black

more common but recessive

1. decreased expression of ASIP
2. no MC1R blockage
3. eumelanin

Question 22

MC1R gain of function

Answer 22

black

least common

1. MC1R blocks ASIP binding
2. no MSH block
3. eumelanin

Question 23

K locus

Answer 23

black

MOST common in dogs - dominant

beta defensin mutation (CBD103) prevents ASIP from binding to MCR1
- independent of MC1R and ASIP status

Question 24

how does MC1R status compare to ASIP and K locus status

Answer 24

epistatic

if no MC1R present –> will always get PHEOMELANIN because no cAMP signaling

Question 25

what causes albinism

Answer 25

tyrosinase mutation leading to absent pigment production recessive (rare) pleiotropic - affects eyesight

Question 26

OCA type 1

Answer 26

oculocutaneous albinism caused by tyrosinase mutations ex. temperature sensitive mutations in siamese cats (white + diluted black areas in cold regions)

Question 27

what causes brown coat color

Answer 27

TRP-1 mutation leading to inability to catalyze final step of eumelanin production --> "less intense" black pigment no pleiotropic effects

Question 28

what causes cream coat color

Answer 28

OCA type 4 mutations at MATP or SLC45A2 that disrupts tyrosinase trafficking and proton transport to melanosomes

Question 29

what causes dilute coat color

Answer 29

melanophillin mutation that disrupts melanosome transport in melanocytes --> causes clumping of pigment granules leading to dilute color recessive bad pleiotropic effects - lavender foals --> neurologic - collies --> cyclic neutropenia

Question 30

pleiotropy

Answer 30

the production of two or more apparently unrelated effects by a single gene

Question 31

how does white spotting occur

Answer 31

mutations that cause failure of melanocytes to reach certain areas/decreased survival

Question 32

dominant white spotting

Answer 32

tobiano in horses

Question 33

recessive white spotting

Answer 33

white spots in cats, dogs

Question 34

pleiotropic effects of white spotting

Answer 34

deafness - inner ear (stria vascularis) requires melanocytes - no melanocytes migrating to ear (white ears) --> prone to deafness

Question 35

lethal white foal syndrome

Answer 35

overo x overo --> offspring: - solid - overo - overo - lethal white foals have ganglionic megacolon leading to colic immediately after birth (inappropriately innervated gut) concurrent deafness