Genetics and genomics of mammalian pigmentary variation
This presentation is the property of its rightful owner.
Sponsored Links
1 / 29

Genetics and genomics of mammalian pigmentary variation PowerPoint PPT Presentation


  • 57 Views
  • Uploaded on
  • Presentation posted in: General

Genetics and genomics of mammalian pigmentary variation. Human Genome Meeting June 3, 2006. Greg Barsh Department of Genetics Stanford University School of Medicine. pleiotropic effects of lethal yellow ( A y ). Biology of Pigmentation and its Applications to disease….

Download Presentation

Genetics and genomics of mammalian pigmentary variation

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Genetics and genomics of mammalian pigmentary variation

Genetics and genomics of mammalian pigmentary variation

Human Genome Meeting

June 3, 2006

Greg BarshDepartment of Genetics

Stanford University School of Medicine


Biology of pigmentation and its applications to disease

pleiotropic effects of lethal yellow (Ay)

Biology of Pigmentation and its Applicationsto disease…

MC4R:+/-(siblings)+/+

~4% of individuals with severe childhood-onset obesity (Farooqi et al.)


Genetics and genomics of mammalian pigmentary variation

Melanocyte development and biochemistry

Pigment type switching and genetics


Genetics and genomics of mammalian pigmentary variation

Molecular causes of Mc1r loss-of-function

DG104

red cow

(Klungland, 1995)

DC183

yellow mouse

(Robbins, 1993)

R306ter

Irish Setter

(Newton, 2000)

C33T

red chicken

(Takeuchi, 1996)

S83F

chestnut horse

(Marklunk, 1996)

A240T

red pig

(Kijas, 1998)

R151C

red hair

(Rees, 1997)


Genetics and genomics of mammalian pigmentary variation

What causes pigmentation patterns?

Arctic Lemming


Control of pigment distribution by agouti alleles in time and space

Control of pigment distribution by Agouti allelesin timeand space

dorsum

1-34-67-9

days of post-natal hair growth

ventrum

light-bellied Agouti (AW)

Agouti (A)

black-and-tan (at)


Genetics and genomics of mammalian pigmentary variation

Regional promoters give rise to pigment patterns


Genetics and genomics of mammalian pigmentary variation

Reversal of an inverted duplication in the AW to A mutation


Genetics and genomics of mammalian pigmentary variation

Adaptive coloration in Peromyscus (H. Hoekstra)

Sand Hills of Nebraska:"Wide band" Agouti(P. maniculatus)

Santa Rosa Beach Mouse

Perdido Key Beach Mouse

Alabama Beach Mouse

St. Andrew Beach Mouse

Choctawhatchee Beach Mouse

open sand dunes,

lighter sand

increased cover,

darker sand

Coastal dunes and barrier islands (P. polionotus)


Genetics and genomics of mammalian pigmentary variation

Pigment type-switching in other animals


Genetics and genomics of mammalian pigmentary variation

Dominance of Agouti alleles in Mice and Dogs (Little, 1969)

Mice

Dogs


Genetics and genomics of mammalian pigmentary variation

X

Black-and-tan

Finnish Lapphund

Black

Finnish Lapphund

(Fawn-colored

Greyhound;

Fawn-colored

Boxer)

(Newfoundland;

Black Labrador;

Dalmation)


Genetics and genomics of mammalian pigmentary variation

The Cornell cross (Lust, Todhunter)

40

16 non-black

16 black


Genetics and genomics of mammalian pigmentary variation

Genome scan: a new black locus (K) in dogs

(Cornell cross)18 animals,155 markers:LOD 8.6 attheta = 0


Genetics and genomics of mammalian pigmentary variation

Epistasis instead of dominance

Mice

Dogs


Genetics and genomics of mammalian pigmentary variation

Genetics of domestic dogs as a model system

Domestication from wolves about 15,000 years ago

Patterns of linkage disequilibrium

(Linblad-Tohet al., 2005)

Large Ne; short LD(like humans)

Establishment of modern breeds about 250 years ago

Small Ne; long LD(like lab mice)

(1) Establish rough subchromosomal position by association within breeds

(2) Fine-map by association across breeds (assuming ancestral allele)


Genetics and genomics of mammalian pigmentary variation

Single dogs for association study


Genetics and genomics of mammalian pigmentary variation

K maps to a gene cluster encoding secreted cysteine-rich proteins

Dog 16 (356 kb)

25kb

Reversion mapping interval (200 kb)

LD mapping interval (9 kb)

widely expressed

expressed in skin

signal peptide

mature peptide

mutated in fawn vs. black


Genetics and genomics of mammalian pigmentary variation

How does the K locus work?

AgoutiMc1rKPhenotype

ay+fawn (k)Pheomelanic

ay+black (K)Eumelanic

a (lof)+K or kEumelanic

aye (lof)K or kPheomelanic

K

?

?

K


Genetics and genomics of mammalian pigmentary variation

brindled (kbr) is an allele of the K locus

fawn or red (k)

brindle (kbr)

Black (K)

k < kbr < K


Genetics and genomics of mammalian pigmentary variation

Brindled (kbr) is a segmental duplication

fawn (k): ancestral allele (wolves, coyotes

Black (K): derivative allele

(~10,000 years ago)

Brindled (kbr):

segmental duplication

(~1000 years ago)


Genetics and genomics of mammalian pigmentary variation

Epigenetic control of brindled stripes

black stripe

yellow stripe


Genetics and genomics of mammalian pigmentary variation

Building blocks for pigment patterns

Agouti

Black (K)


Genetics and genomics of mammalian pigmentary variation

Acknowledgements

Cornell

George LustRory TodhunterMichael Olivier

Saskatchewan

Sheila Schmutz

Harwell

Bruce Cattanach

Chris Kaelin

Sophie Candille

Julie Kerns


  • Login