Evolution in dogs

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Evolution in dogs

• CS-374
• Abhinay Nagpal
• abhinay_at_stanford.edu

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Papers that are discussed

• Evolution in dogs
• A single IGF1 allele is a major determinant of
  small size in dogs
• Genome-wide SNP and haplotype analyses reveal a
  rich history underlying dog domestication

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Why are we interested in evolution of dogs?

• Dogs show greatest variation in size in
  vertebrates.
• It has been attributed to domestication
• Dogs have high similarity of multi locus
  haplotypes present in wolves in middle east

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A Single IGF1 Allele Is a Major Determinant of
Small Size in Dogs
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The Experiment
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Identifying QTL

• Quantitative trait loci (QTLs)-gt stretches of DNA
  linked to the genes that tie to a phentoype trait
• 2 radiographic skeletal measurements for size and
  shape-gt two QTL (FH2017 at 37.9 Mb and FH2295 at
  43.5 Mb) strongly associated with body size

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Relationships of skeletal size, SNP markers, IGF1
haplotype, and serum levels of the IGF1 protein
in PWDs
A Single IGF1 Allele Is a Major Determinant of
Small Size in Dogs
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Mixed model for Portuguese water dog fine-mapping

• Y is the vector of the skeletal size trait
• a is a vector of fixed effect, the SNP effect we
  are testing
• u is a vector of random effect reflecting the
  polygenetic background
• X and Z are known incidence matrices relating the
  observations to fixed and random effects,
  respectively.
• The variance in the model can be expressed as

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IGF1 Influences Size of dogs

• Average heterozygosity in small dogs near IGF1 is
  only 25 of that in large dogs
• A narrow precise genomic region holds the variant
  responsible for small size.

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Evidence of Association
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FISHERS EXACT TEST

• Computes directly the probability of observing a
  particular set of frequencies in a 2 x 2 table
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• Returns inflated p values
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Mann Whitney
Consider a hare and tortoise race in which the
outcomes are as follows H H H H H H H H H T T T
T T T T T T T H H H H H H H H H H T T T T T T T T
T Median tortoise here comes in at position
19 Median hare comes in at position
20. However, the value of U (for hares) is
100 Value of U(for tortoises) is 261
http//en.wikipedia.org/wiki/MannE28093Whitney_
U
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Mann Whitney V.S Fishers Test
Cumulative distribution function for Fishers
exact test and Mann-Whitney U statistic
calculated from 83 genomic control SNPs genotyped
in small and giant dogs
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Association of body size and frequency of the SNP
5 A allele
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Fixation index

• Measure of the diversity of randomly chosen
  alleles within the same sub-population relative
  to that found in the entire population.

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Findings

• IGF1 haplotype substantially contributes to size
• Size diversity was present early in the history
  of domestication
• Ancestral small dog IGF1 haplotype was spread
  over a large geographic area by trade and human
  migration

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Genome-wide SNP and haplotype analyses reveal a
rich history underlying dog domestication
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Highlights

• The dog is a striking example of variation
  under domestication
• Evolutionary processes poorly understood
• Did dogs first evolve in East Asia?

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Data

• Survey of 48000 SNPs in dogs and wolves(grey
  wolf)
• Typed from 912 dogs - 85 breeds 225 grey wolves
• 11 globally distributed population

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Dog Evolution
http//www.sciencemag.org/content/276/5319/1687.fu
ll
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Bayesian clustering Neighbor joining trees
An example tree with 4 data points. The
clusterings (1 2 3)(4) and (1 2)(3)(4) are
tree-consistent partitions The clustering (1)(2
3)(4) is not a treeconsistent partition http//ww
w.gatsby.ucl.ac.uk/heller/bhcnew.pdf
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Bayesian Hierarchical Clustering Algorithm
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Neighbor Joining Trees
distance matrix
http//www.icp.ucl.ac.be/opperd/private/neighbor.
html
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We have in total 6 elements (N6).
Step 1 We calculate the net divergence r (i) for
each element from all other elements r(A)
5476830 r(B) 42 r(C) 32 r(D) 38 r(E)
34 r(F) 44
Step 2 Now we calculate a new distance matrix
using for each pair M(ij)d(ij) - r(i)
r(j)/(N-2) or in the case of the pair
A,B M(AB)d(AB) -(r(A) r(B)/(N-2) -13
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Step 3 Choose as neighbors pairs for which Mij
is the smallest. gt A and B and D and E. Let's
take A and B as neighbors and we form a new node
called U. Calculate the branch length from the
internal node U to A and B.
S(AU) d(AB) / 2 r(A)-r(B) / 2(N-2) 1
S(BU) d(AB) -S(AU) 4
Step 4 Now we define new distances from U to
each other terminal node d(CU) d(AC) d(BC)
- d(AB) / 2 3 d(DU) d(AD) d(BD) - d(AB) /
2 6 d(EU) d(AE) d(BE) - d(AB) / 2 5
d(FU) d(AF) d(BF) - d(AB) / 2 7
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Neighbour-joining trees of domestic dogs and
grey wolves.
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Analysis of molecular variance (AMOVA)
Variation within breed 65 of total
variation/diversity Variation within breed
grouping 31 of total variation/diversity Variat
ion between breed groupings 3.8 of total
variation/diversity
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Principal component analysis (PCA) of 48,036 SNPs
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Observations
For 5-SNP haplotype windows haplotype sharing
higher between modern dog breeds and Middle
Eastern wolves For 15-SNP windows the
majority of breeds show the most sharing with
Middle Eastern wolves This has dog breeds of
diverse geographic origins Only two east Asian
breeds (Akita and chow chow) had higher sharing
with Chinese wolves
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Findings

• Haplotype sharing higher in modern dog breeds
  and
• Middle Eastern wolves
• Eg basenji, chihuahua, basset hound and borzoi
• Neighbour-joining trees excellent for breed
  history diversity
• Breed groupings mirror breed classification
  based on form and function

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References
http//pritch.bsd.uchicago.edu/publications/struct
ure.pdf
http//www.nature.com/nature/journal/v464/n7290/ex
tref/nature08837-s1.pdf
A Single IGF1 Allele Is a Major Determinant of
Small Size in Dogs Sutter et al.
Science,2007 Genome-wide SNP and haplotype
analyses reveal a rich history underlying dog
domestication. vonHoldt et al. nature,2010. http
//en.wikipedia.org/wiki/Fisher's_exact_test
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Backup slide mann whitney
Consider another hare and tortoise race, with 19
participants of each species in which the
outcomes are as follows H H H H H H H H H T T T
T T T T T T T H H H H H H H H H H T T T T T T T T
T The median tortoise here comes in at position
19, and thus actually beats the median hare
which comes in at position 20. However, the
value of U (for hares) is 100 (9 Hares
beaten by (x) 0 tortoises) (10 hares beaten by
(x) 10 tortoises) 0 100 100 Value of U(for
tortoises) is 261 (10 tortoises beaten by 9
hares) (9 tortoises beaten by 19 hares) 90
171 261 Consulting tables, or using the
approximation below shows that this U value
gives significant evidence that hares tend to do
better than tortoises (p lt 0.05, two-tailed).
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