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Preliminary synteny mapping for dog genome

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contiguous in dog and human. nearly coincident breaks in chicken, mouse and rat ... Dog reveals ancient duplication. A 4 Mb region on dog chr21 shows strong ... – PowerPoint PPT presentation

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Title: Preliminary synteny mapping for dog genome


1
Preliminary synteny mapping for dog genome
  • Bob Handsaker
  • Michael Kamal
  • Broad Institute

2
Topics
Methodology Preliminary synteny maps Future
directions Genome features and evolution
3
Topics
Methodology Preliminary synteny maps Future
directions Genome features and evolution
4
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)

5
Alignment Clusters
  • Example alignments surrounding OCTN gene family

D11
M2
M2
6
Topics
Methodology Preliminary synteny maps Future
directions Genome features and evolution
7
Doghuman - more conserved synteny than rodents
Key Dog Ref
H M R
8
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!
9
Celera vs Broad Dog chrom 1
Celera
Broad
Novel segments
Minimum segment size of 500K
10
Dog identifies human specific events
Human 17 vs Mouse11
Human
Mouse
Mouse
Rat
Human
Dog
11
Dog specific events Chicken as outgroup
Gap in chicken
Dog specific
Chicken, Human, Mouse, Rat vs Dog
12
Dog-centric synteny for 5 species
Chicken, Human, Mouse,Rat vs Dog
13
Topics
Methodology Preliminary synteny maps Future
directions Genome features and evolution
14
Possible breakpoint reuse?
  • contiguous in dog and human
  • nearly coincident breaks in chicken, mouse and
    rat

What sanity checks are needed?
15
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
16

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
17
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?
18
Topics
Methodology Preliminary synteny maps Future
directions Genome features and evolution
19
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
20
Genome features and evolution
Orthologous regions GC content CpG content
(human mouse) 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??
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