a novel fine-scale human recombination map reveals sex ...€¦ · map reveals sex differences...
TRANSCRIPT
![Page 1: A novel fine-scale human recombination map reveals sex ...€¦ · map reveals sex differences Chenling Antelope, Graham Coop University of California, Davis. Recombination is an](https://reader030.vdocuments.net/reader030/viewer/2022040619/5f2c510ae0352f408311a7f5/html5/thumbnails/1.jpg)
A novel f ine-scale human recombinat ion map reveals sex dif ferences
Chenling Antelope, Graham Coop
University of California, Davis
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Recombinat ion is an Important Process
Recombinat ion is a fundamental cel lular and molecular process
- Chromosomal segregation
- Hotspots (PRDM9)
Recombinat ion is a fundamental genet ic process
- Increase Genetic Variance
- Breaks up epistatic interactions
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Sexual Dimorphism in Human Meiosis
MaleFemale
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Sexual Dimorphism in Human Recombinat ion Rate
Number of crossovers per individual in the AGRE (Aut ism Genet ic Resource Exchange) pedigree
Fledel-Alon, A. et al. Variation in human recombination rates and its genetic determinants. PloS one 6, e20321 (2011).Fledel-Alon, A. et al. Variation in human recombination rates and its genetic determinants. PloS one 6, e20321 (2011).
Chromosomal Position Mb
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Fine Scale Recombinat ion Rate
Sequence Specif icity -> Similar
Fine Scale Chromatin State -> Dif ferent
1. New method for inferring sex-specif ic f ine scale recombination rate
2. Amount of f ine scale recombination rate sharing
3. Fine-scale recombination rate around genes (as a proxy for chromatin state)
4. Interaction between large scale and f ine scale recombination variation
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3774 Females, 3781 Males
Fledel-Alon, A. et al. Variation in human recombination rates and its genetic determinants. PloS one 6, e20321 (2011).Fledel-Alon, A. et al. Variation in human recombination rates and its genetic determinants. PloS one 6, e20321 (2011).
41745 Females, 30184 Males
Kong, A, Thorleifsson, G, Frigge, ML & Masson, G. Common and low-frequency variants associated with genome-wide recombination rate. Nature ? (2014).
Data & Method
Kong, A, Thorleifsson, G, Gudbjartsson, DF & Masson, G. Nature (2010).
We apply a Gibbs Sampler Method i terat ively in order to estimate the posit ion of of a recombinat ion event and recombinat ion rates in genomic windows simul taneously.
Male rate and female rate estimated using the same method independently.
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Hotspot Sharing
Mal
e C
ateg
ory
Female Category
Hotspots are defined by the fold increase of a 10kb window compared to the 1Mb window (not including target window) around it.
Mal
e R
ecom
bin
atio
n In
tens
ity
Female Recombination Intensity
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Hotspot Sharing
Mal
e C
ateg
ory
Female Recombination Intensity
Mal
e R
ecom
bin
atio
n In
tens
ity
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Hotspot Sharing
Mal
e C
ateg
ory
Female CategoryFemale Recombination EnrichmentFemale Recombination EnrichmentMale Recombination Intensity
Fem
ale
Rec
omb
inat
ion
Inte
nsi
ty
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Recombinat ion Rate Along Transcript
Female Male
Rec
omb
inat
ion
Rat
e cM
/Mb
5'U
TR1
st E
xon
1st
Intr
on2
nd E
xon
2nd
Intr
on3
rd E
xon
3rd
Intr
on4
th E
xon
4th
Intr
on5
th E
xon
5th
Intr
on6
th E
xon
6th
Intr
on7
th E
xon
7th
Intr
on8
th E
xon
8th
Intr
on9
th E
xon
9th
Intr
on1
0th
Exo
n1
0th
Intr
on3
'UTR
5'U
TR1
st E
xon
1st
Intr
on2
nd E
xon
2nd
Intr
on3
rd E
xon
3rd
Intr
on4
th E
xon
4th
Intr
on5
th E
xon
5th
Intr
on6
th E
xon
6th
Intr
on7
th E
xon
7th
Intr
on8
th E
xon
8th
Intr
on9
th E
xon
9th
Intr
on1
0th
Exo
n1
0th
Intr
on3
'UTR
Gold: Exon
Green: Int ron
Red: 5'UTR
Blue: 3'UTR
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Distance (bp) from Transcription Start Site
Rec
omb
inat
ion
Rat
e cM
/Mb
Recombinat ion Rate Near Transcript ion Start Site
0.5
21
1.5
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Variat ion Along Chromosome Arm
Distance (bp) from Transcription Start Site
Female 1/5 of Chromosome
Closest to Centromere
Rec
omb
inat
ion
Rat
e cM
/Mb
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Variat ion Along Chromosome Arm0
.3-2
.0 c
M/M
b0
.7-2
.4 c
M/M
b
TelomericCentromeric
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Conclusions:
- ~50% of recombination hotspots are shared.
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Conclusions:
- ~50% of recombination hotspots are shared.
- Male and female rate are correlated in shared hotspots.
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Conclusions:
- ~50% of recombination hotspots are shared.
- Male and female rate are correlated in shared hotspots.
- Recombination rate covaries with sequence function.
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Conclusions:
- ~50% of recombination hotspots are shared.
- Male and female rate are correlated in shared hotspots.
- Recombination rate covaries with sequence function.
- Fine scale and broad scale recombination rate variation interact with each
other.
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Conclusions:
- ~50% of recombination hotspots are shared.
- Male and female rate are correlated in shared hotspots.
- Recombination rate covaries with sequence function.
- Fine scale and broad scale recombination rate variation interact with each
other.
Further quest ions:
- What mechanisms are causing the recombination patterns we are seeing?
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Thanks to
Coop Lab
Mol ly Przeworski
I will be moving to UC Berkeley next year to start my phD in the Computational Biology Graduate Group!
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Hotspot Sharing%
Shar
ed
>1
>2
>3
>4
>6
>8
>1
2
>1
9
>2
6
>3
9
>5
8
>1
>2
>3
>4
>6
>8
>1
2
>1
9
>2
6
>3
9
>5
8
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Simulat ion Using HapMap
Chromosomal Position Kb (Starting Chr1 99981 Kb)
Rec
omb
inat
ion
Rat
e cM
/Mb
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Recombinat ion Rate in Annotat ion Categories R
ecom
bin
atio
n R
ate
cM/M
b
10 K rate / 1M background (Male)
Female Male
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Hotspot Counts
187K 9998 4906 2867 2929 1492 1350 646 268 104 29 9 6
14K 2382 1335 826 776 404 344 52 14 1 0 0166
6243 1211 837 542 618 332 305 136 51 17 3 1 0
3207 677 491 400 552 317 278 55 21 2 0 0148
3261 625 582 484 756 449 525 265 85 25 7 0 0
1472 260 278 256 386 306 343 102 33 5 0 0244
1240 188 217 226 399 344 482 411 192 59 6 0 0
521 72 85 88 168 179 285 214 95 15 0 0349
183 13 15 14 37 48 100 130 115 20 1 0152
71 8 3 5 10 8 21 31 50 53 29 1 0
25 1 0 0 0 1 3 7 10 11 1 04
5 0 0 0 2 0 0 0 0 0 3 1 0
2 0 0 0 0 0 0 0 0 0 0 00
10
K r
ate
/ 1
M b
ackg
roun
d (F
emal
e)
10 K rate / 1M background (Male)
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Correlat ion Between Expression and Recombinat ionTr
ansc
rip
t R
ecom
bin
atio
n R
ate
cM/M
b
Rank in Expression
Slope -5.15e-3
P value 2.58e-2
Slope -1.087e-2
P value 2.53e-06