MAGIC	
  
	
  
An	
  innova(ve	
  approach	
  to	
  
dissec(ng	
  the	
  gene(c	
  control	
  
of	
  complex	
  traits	
  ...
Mapping	
  in	
  mul(-­‐founder	
  experimental	
  popula(ons	
  
MAGIC	
  
Mul(-­‐parent	
  Advanced	
  Gene(c	
  InterCr...
Variety	
   Reason	
  for	
  inclusion	
  
Alchemy	
   Yield,	
  disease	
  resistance,	
  so[	
  feed	
  type,	
  breedin...
The	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
28à210à315	
  complete	
  pedigree	
  
@NIABTAG	
  
#bgri2014	
  
The	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
28à210à315	
  
descendants	
  of	
  Founder	
  1	
  
@NIABTAG	
  
#bgri20...
MAGIC	
  F2	
  derived	
  	
  
F2	
  &	
  self	
   Elite	
  MAGIC	
  &	
  self	
  
P	
  (no	
  recomb)	
   0.241	
   0.036...
26512	
  SNPs	
  
AM	
  panel	
  
allele freqs in lines
(AAm * 2 + ABm)/((AAm + ABm + BBm) * 2)
Frequency
0.2 0.4 0.6 0.8 ...
90K	
  genotypes	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  AM	
  panel	
  
MAGIC	
  
@NIABTAG	
  
#bgri2014	
  
YR	
  resistance	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
22nd	
  August	
  2011	
  ‘Warrior’	
  Pst	
  race	
  
...
YR	
  resistance	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
0	
   1
	
  
2	
   3-­‐4	
   9	
  5-­‐6	
   7-­‐8	
  
Y...
MAGIC line means
BLUP (log2)
Frequency
0.0 0.5 1.0 1.5 2.0 2.5 3.0
050100150200250300
Parent	
  1	
  
Hereward	
  
Parent	...
YR	
  resistance	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
YR	
  field	
  assessment	
  –	
  natural	
  infec(on	
 ...
YR	
  resistance	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
Mapping	
  hits	
  -­‐	
  YR	
  glasshouse	
  seedling	...
YR	
  resistance	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
Mapping	
  hits	
  -­‐	
  YR	
  seedling	
  and	
  field...
YR	
  resistance	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
3	
  large	
  effects	
  observed	
  	
  
0 2
0.00.51.01...
Favourable	
  alleles	
  are	
  dispersed	
  
YR	
  resistance	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
@NIABTAG	...
YR	
  resistance	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
Marco	
  Scutari,	
  UCL	
  
@NIABTAG	
  
#bgri2014	
  
YR	
  resistance	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
@NIABTAG	
  
#bgri2014	
  
TGW	
  QTL	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
Kukri_c22361_2477 Kukri_c3075_391
Kukri_c7794_1247 Kukri_c959...
Adap(ve	
  traits	
  -­‐	
  NIAB	
  Elite	
  MAGIC	
  popula(on	
  
@NIABTAG	
  
#bgri2014	
  
4
6
8
10
1947 1957 1967 1977 1987 1997 2007
NIAB	
  Diverse	
  MAGIC	
  popula(on	
  
@NIABTAG	
  
#bgri2014	
  
The	
  future	
  is	
  MAGIC	
  	
  
Acknowledgements	
  
• 	
  NIAB	
  Trust	
  &	
  pre-­‐breeding	
  
team	
  
• 	
  Le...
Methods	
  of	
  analysis	
  must	
  account	
  for	
  family	
  structure	
  
•  One-­‐way	
  ANOVA	
  and	
  linear	
  r...
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2014 bgri bentley presentation

  1. 1. MAGIC     An  innova(ve  approach  to   dissec(ng  the  gene(c  control   of  complex  traits  in  wheat         Alison  Bentley,  P  Howell,  J  Cockram,  G  Rose,  T   Barber,  R  Horsnell,  N  Gosman,  P  Bansept,  M   Scutari,  A  Greenland  and  I  Mackay     @NIABTAG   BGRI  Technical  Workshop  March  2014  #bgri2014  
  2. 2. Mapping  in  mul(-­‐founder  experimental  popula(ons   MAGIC   Mul(-­‐parent  Advanced  Gene(c  InterCross     • An  extension  of  the  Advanced  Intercross  (Darvasi  &   Soller,  1995)   • Diverse  popula(on:  good  for  mul(ple  interac(ng   traits  and  loci   • QTL  detec(on  in  early  genera(ons   • Fine  mapping  in  later  genera(ons   • Increased  diversity  means  more  QTL  can  be  mapped   • Increased  mapping  precision   @NIABTAG   #bgri2014  
  3. 3. Variety   Reason  for  inclusion   Alchemy   Yield,  disease  resistance,  so[  feed  type,  breeding   parent   Brompton   1BL/1RS,  hard  feed  type,  OWBM  resistance   Claire   Slow  apical  development,  so[  biscuit/dis(lling   type   Hereward   High  quality  benchmark  Gp1  bread  making  type   Rialto   1BL/1RS,  Gp2  moderate  bread  making  type   Robigus   High  yielding,  so[  biscuit/dis(lling  type,  OWBM   resistance   Soissons   Early  flowering  French  Gp2  bread  making  type   Xi19   Faculta(ve,  high  quality  Gp1  bread  making  type   The  NIAB  Elite  MAGIC  popula(on   Designed  with  a  focus  on  mapping  QTL  segrega(ng  in   current  elite  UK  germplasm   @NIABTAG   #bgri2014  
  4. 4. The  NIAB  Elite  MAGIC  popula(on   28à210à315  complete  pedigree   @NIABTAG   #bgri2014  
  5. 5. The  NIAB  Elite  MAGIC  popula(on   28à210à315   descendants  of  Founder  1   @NIABTAG   #bgri2014  
  6. 6. MAGIC  F2  derived     F2  &  self   Elite  MAGIC  &  self   P  (no  recomb)   0.241   0.036   #  tracts     2.6   4.7   #  founders   2   3.5   The  NIAB  Elite  MAGIC  popula(on   @NIABTAG   #bgri2014  
  7. 7. 26512  SNPs   AM  panel   allele freqs in lines (AAm * 2 + ABm)/((AAm + ABm + BBm) * 2) Frequency 0.2 0.4 0.6 0.8 1.0 020406080100 15968  SNPs   MAGIC   90K  genotypes  -­‐  NIAB  Elite  MAGIC  popula(on   @NIABTAG   #bgri2014  
  8. 8. 90K  genotypes  -­‐  NIAB  Elite  MAGIC  popula(on  AM  panel   MAGIC   @NIABTAG   #bgri2014  
  9. 9. YR  resistance  -­‐  NIAB  Elite  MAGIC  popula(on   22nd  August  2011  ‘Warrior’  Pst  race   @NIABTAG   #bgri2014  
  10. 10. YR  resistance  -­‐  NIAB  Elite  MAGIC  popula(on   0   1   2   3-­‐4   9  5-­‐6   7-­‐8   YR  glasshouse  seedling  test  –  ‘Warrior’  inocula(on   @NIABTAG   #bgri2014  
  11. 11. MAGIC line means BLUP (log2) Frequency 0.0 0.5 1.0 1.5 2.0 2.5 3.0 050100150200250300 Parent  1   Hereward   Parent  2   Robigus   Resistant   progeny   YR  resistance  -­‐  NIAB  Elite  MAGIC  popula(on   YR  glasshouse  –  distribu(on  of  disease  scores   BLUP  (log2  adjusted  scores)   Frequency   @NIABTAG   #bgri2014  
  12. 12. YR  resistance  -­‐  NIAB  Elite  MAGIC  popula(on   YR  field  assessment  –  natural  infec(on     1 2 3 4 5 6 7 0.00.51.01.52.02.53.0 Glasshouse and field (yellow rust) disease scores field yellow rust yellowrustseedlingtest Field  YR  scores   Seedling  YR  scores   @NIABTAG   #bgri2014  
  13. 13. YR  resistance  -­‐  NIAB  Elite  MAGIC  popula(on   Mapping  hits  -­‐  YR  glasshouse  seedling  test     @NIABTAG   #bgri2014  χ2    adjusted   χ2    not  adjusted  
  14. 14. YR  resistance  -­‐  NIAB  Elite  MAGIC  popula(on   Mapping  hits  -­‐  YR  seedling  and  field  tests     @NIABTAG   #bgri2014    Gp  1      Gp  2        Gp  3    Gp  4      Gp  5    Gp  6      Gp  7                unlinked   -­‐log10(P)   Gp  1      Gp  2    Gp  3    Gp  4    Gp  5      Gp  6      Gp  7                unlinked     -­‐log10(P)   Seedling  resistance   Field  resistance  
  15. 15. YR  resistance  -­‐  NIAB  Elite  MAGIC  popula(on   3  large  effects  observed     0 2 0.00.51.01.52.02.53.0 RAC875_c50347_258 genotype class log2yellowrust 0 1 2 0.00.51.01.52.02.53.0 BobWhite_c5756_516 genotype class log2yellowrust @NIABTAG   #bgri2014  
  16. 16. Favourable  alleles  are  dispersed   YR  resistance  -­‐  NIAB  Elite  MAGIC  popula(on   @NIABTAG   #bgri2014  
  17. 17. YR  resistance  -­‐  NIAB  Elite  MAGIC  popula(on   Marco  Scutari,  UCL   @NIABTAG   #bgri2014  
  18. 18. YR  resistance  -­‐  NIAB  Elite  MAGIC  popula(on   @NIABTAG   #bgri2014  
  19. 19. TGW  QTL  -­‐  NIAB  Elite  MAGIC  popula(on   Kukri_c22361_2477 Kukri_c3075_391 Kukri_c7794_1247 Kukri_c9595_242 RAC875_c767_4007 RFL_Contig2605_672 RFL_Contig2605_693 RFL_Contig4441_505 RFL_Contig4441_627 wsnp_Ex_rep_c67878_66584488 Excalibur_c37240_609 70.9 BS00003881_51 BS00004377_51 Kukri_c50910_86671.5 BS00065309_51 BS00072945_51 Excalibur_c47557_418 wsnp_Ex_c19454_28409258 IACX8469 BS00011122_51 BS00023089_51 BS00041481_51 BS00064632_51 BS00078715_51 BS00086046_51 BS00087178_51 BS00089169_51 Ex_c50864_326 Excalibur_c1492_1282 Excalibur_c61509_69 Excalibur_rep_c66355_301 Excalibur_s105534_234 IAAV1263 IAAV1346 IAAV1385 IAAV5967 IAAV6535 IAAV894 JD_c6195_347 Ku_c13637_545 Ku_c71238_1537 Kukri_c1281_515 Kukri_c16868_1062 Kukri_c25562_1826 Kukri_c30819_246 RAC875_c49166_240 RAC875_c5819_1450 RAC875_c58848_60 TA003858-0637 TA004097-0977 tplb0047k12_1370 wsnp_Ex_c12288_19625413 wsnp_Ex_c35545_43677576 wsnp_Ex_c43887_50077773 wsnp_Ex_c590_1176609 wsnp_Ex_rep_c102173_87395725 wsnp_Ex_rep_c105612_89983181 wsnp_Ex_rep_c67218_65729639 wsnp_Ex_rep_c67692_66357763 wsnp_Ku_rep_c68351_67302372 IAAV6992 IACX422 BS00013851_51 BS00099290_51 Excalibur_c49239_97 TA004032-0298 BS00022412_51 BS00024191_51 BS00033795_51 BS00036211_51 BS00065079_51 BS00072146_51 BS00088375_51 Ex_c8482_488 Excalibur_c16840_3454 Excalibur_c37358_676 Excalibur_c60816_99 IAAV2245 IAAV3994 IACX8190 Ku_c104762_377 Kukri_c33967_97 Kukri_c38882_391 Kukri_rep_c70185_854 Ra_c4452_3073 RAC875_c13778_650 RAC875_c29487_369 RAC875_rep_c76107_118 TA001414-0867 TA002574-0890 Tdurum_contig78006_158 wsnp_BE403421A_Ta_2_1 wsnp_Ex_c1104_2118684 wsnp_Ex_c11446_18468102 wsnp_Ex_c18965_27868480 wsnp_Ex_c19476_28434084 wsnp_Ex_c29350_38393488 wsnp_Ex_c31711_40468407 wsnp_Ex_c41551_48349585 wsnp_Ex_c590_1176006 wsnp_Ex_rep_c67605_66248628 wsnp_Ex_rep_c69901_68864080 wsnp_JD_c5028_6151168 wsnp_Ku_rep_c71238_70957970 wsnp_Ra_rep_c100410_86374467 BobWhite_c20706_135 BobWhite_c7156_643 BS00064203_51 BS00068469_51 Ex_c66635_550 wsnp_Ku_c27273_37219950 BS00064873_51 72.6 BS00009985_51 BS00043716_51 Kukri_c14901_114 BS00011034_51 BS00022120_51 Excalibur_c34574_452 73.2 wsnp_Ku_c2329_4474766 wsnp_Ku_c8394_14267750 wsnp_Ra_c44015_50539749 BS00022605_51 wsnp_Ku_c3354_6228393 wsnp_Ku_c3354_6228863 wsnp_Ku_c9388_15743434 wsnp_Ra_c31062_40243185 73.8 BS00038646_51 Ku_c9262_902 BS00084250_51 Kukri_c2700_1137 Kukri_c44260_577 TA004297-0876 wsnp_Ex_c2350_4403690 wsnp_Ex_c341_667884 wsnp_Ku_c2700_5121331 wsnp_Ku_c2700_5121383 Kukri_c18260_345 Kukri_c9262_401 BS00072903_51 BS00082211_51 Excalibur_rep_c69275_346 GENE-3945_245 RAC875_c62614_191 TA012395-0819 Tdurum_contig42125_5692 wsnp_Ex_c30264_39202224 wsnp_Ku_c3450_6387847 Ku_c69999_111 74.4 TGRWT 0 5 10 15 TGRWT Avalon  x  Cadenza   5  chromosomes   7  QTL     MAGIC   24  linkage  groups     124  SNPs   Harriet  Benbow   University  of  Bristol   @NIABTAG   #bgri2014  
  20. 20. Adap(ve  traits  -­‐  NIAB  Elite  MAGIC  popula(on   @NIABTAG   #bgri2014  
  21. 21. 4 6 8 10 1947 1957 1967 1977 1987 1997 2007 NIAB  Diverse  MAGIC  popula(on   @NIABTAG   #bgri2014  
  22. 22. The  future  is  MAGIC     Acknowledgements   •   NIAB  Trust  &  pre-­‐breeding   team   •   Lesley  Boyd   •   Wayne  Powell   •   Colin  Cavanagh  &  Emma  Huang   •   Harriet  Benbow   •   Keith  Edwards/Sacha  Allen   •   Donal  O’Sullivan   •   RAGT,  KWS  and  Limagrain   @NIABTAG   #bgri2014  
  23. 23. Methods  of  analysis  must  account  for  family  structure   •  One-­‐way  ANOVA  and  linear  regression  fail  to   account  for  family  structure   •  Exploit  hierarchical  pedigree  structure:   extremely  easy     Although  MAGIC  is  very  uniform,  lines  are  s(ll     clustered  within  funnel  crosses  so  there  is  s(ll  a   need  to  correct  for  structure.       Because  the  NIAB  popula(on  has  followed  a   very  specific  crossing  scheme,  this  adjustment  is   very  simple.         Checked  with  gene  drop  simula(ons:   hrp://www.niab.com/pages/id/376/GeneDrop     false positives from simple regression: 10,000 sets p value Frequency 0.0 0.2 0.4 0.6 0.8 1.0 02004006008001000 Dist  of  p-­‐values  under  the  null  hypothesis   with  no  correc(on  –  simulated.   false positives from adjusted regression: 10,000 sets p value Frequency 0.0 0.2 0.4 0.6 0.8 1.0 02004006008001000 Dist  of  p-­‐values  under  the  null   hypothesis  with  correc(on  –  simulated.   Perfect  correc(on.  

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