Preliminary synteny mapping for dog genome

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Preliminary synteny mapping for dog genome

• Bob Handsaker
• Michael Kamal
• Broad Institute

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Topics
Methodology Preliminary synteny maps Future
directions Genome features and evolution
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Topics
Methodology Preliminary synteny maps Future
directions Genome features and evolution
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Methodology

• Full pairwise genomic alignments (masked)
• Clustering of well-behaved runs of alignments

• Pairwise syntenic maps--key parameters
• minimum allowed segment size,
• maximum alignment-free gap allowed within segment
• Does not rely on feature annotations (genes)

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Alignment Clusters

• Example alignments surrounding OCTN gene family
  

D11
M2
M2
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Topics
Methodology Preliminary synteny maps Future
directions Genome features and evolution
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Doghuman - more conserved synteny than rodents
Key Dog Ref
H M R
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Broadly consistent with Celera 1.5X map
Celera
Broad
D vs H 78
D vs M 130
D vs H 151
D vs M 257
Interchromosomal rearrangements
Different color scheme!
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Celera vs Broad Dog chrom 1
Celera
Broad
Novel segments
Minimum segment size of 500K
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Dog identifies human specific events
Human 17 vs Mouse11
Human
Mouse
Mouse
Rat
Human
Dog
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Dog specific events Chicken as outgroup
Gap in chicken
Dog specific
Chicken, Human, Mouse, Rat vs Dog
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Dog-centric synteny for 5 species
Chicken, Human, Mouse,Rat vs Dog
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Topics
Methodology Preliminary synteny maps Future
directions Genome features and evolution
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Possible breakpoint reuse?

• contiguous in dog and human
• nearly coincident breaks in chicken, mouse and
  rat

What sanity checks are needed?
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Dog reveals ancient duplication

• A 4 Mb region on dog chr21 shows strong
  similarity to two regions on mouse chr2, and two
  regions on human chr11, chr20.

D21
M2
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Non-transitive synteny?

• Not surprising, except
• In human/mouse alignments, the (a) and (b) show
  pair-wise similarity, but not 4-way.

M2(b)
M2(a)
D21
?
H20
H11
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Fine-scale alignments
Estimation of rate of neutral evolution
from alignments of non-functional DNA
Ancient repeats
Lineage specific
4-species syntenic multiple alignments
More generally are features conserved?
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Topics
Methodology Preliminary synteny maps Future
directions Genome features and evolution
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Dog genome smaller than mouse and human
Orthologous 100K windows.
Human/dog 1.17 Mouse/dog 1.05 Rat/dog
1.09 Dog 2.5Gb
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Genome features and evolution
Orthologous regions GC content CpG content
(human gtgtmouse) Recombination rate Repeats Evol
ution rate Dog slow like human? Regional
variation? Correlation to regional variation in
primates/ rodents Correlation to chromosomal
position (dogs chromosomes acrocentric/short)
Functional conservation Identification of
regulatory elements??