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Direct and correlated responses to selection.  1.  EGR ,[object Object],[object Object]
Correlated responses to selection 2.  Body Weight ,[object Object],[object Object],[object Object]
14L and 14H Lines at 14 and 42 Days (S 14 ) 14L 14H 38 g 319 g 172 g 861 g
Life Cycle of Selection Lines
QTL Analysis  F 2  segregating generations Substantial heterosis or dominance for early growth
QTL Analysis  F 2  segregating generations  Substantial additive variation for late growth
Types of Molecular Markers ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
RFLP A a AA  Aa  aa Resulting gel
RAPD A a AA  Aa  aa Resulting gel No PCR product
Microsatellite A a AA  Aa  aa Resulting gel GCC GCC GCC GCC GCC GCC GCC GCC
Molecular marker loci properties Rafalski and Tingey, 1993
Molecular mechanism for crossing-over (Robin Holliday, 1960s): ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Holliday model of chromosome recombination
Experimental designs for  QTL detection ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Backcross design Parental strains X X F 1  strains Backcross Progeny Non-recombinants Recombinants Frequency =  1 - r Frequency =  r m q  m q M Q  M Q m q  M Q M Q  M Q m  q  M Q M Q  M Q m Q  M Q M q  M Q
Bulked segregant analysis 14L 14H F 1 F 2 Bulk 1 Mostly  qq ; enriched for  m , depleted for  M Bulk 2 Mostly  QQ ; enriched for  M , depleted for  m m q  m q M Q  M Q M Q  m  q
Recombinant inbred lines (by selfing)
Recombinant inbred lines (by sibling mating)
Advantages of RI lines ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Grand-daughter design X Grandsire & Grandam(s) X X Sons x random dams (genotyped) Son Son Grand-daughters M 1  Q 1   M 2  Q 2 M x  Q x   M x  Q x M x  Q x   M x  Q x M 1  Q 1   M x  Q x M 2  Q 2   M x  Q x M x  Q x   M x  Q x M 1  Q 1   M x  Q x M x  Q x   M x  Q x M x  Q x   M x  Q x M 2  Q 2   M x  Q x
Determining the  genome sequence  Sequence assembly  Partial digest  Library of bacterial artificial  chromosomes (BACs) with genomic fragments  Alignment of BAC clones > contigs and anchoring On the molecular gene map Sequencing of overlapping  BAC clone fragments  “ Tiling path” > selection of  BAC clones to be sequenced Annotation of genome sequence > prediction of genes
Genomes of human and mouse compared  human: 22 chromosomes + X or Y  mouse: 19 chromosomes + X or Y  homologous segments are color-coded (total >300)  human chromosomes correspond to segments of different mouse chromosomes  e.g.. Segments of chr. 10, 11, 15, 16 and 19 correspond to mouse chromosome 7
Historical perspective: from genetic map to genome sequence
Chicken Chromosome 4 25 cM LEI122  * LEI76 LEI81 ** 270 cM SPP1 Murine SPP1  56.0 cM Chicken  Chromosome 4 Murine  Chromosome 5 (Late Growth QTL) (Cluster 1) (Cluster 2) Cluster 1  - Protein kinase II, glucokinase, VDR,  galactosyltransferase, Ubiquitin C and FGF5 Cluster 2  - Acads, Phkg and Asl Cluster 3  -  ZP3, Zonadhesin , Epo and Actin (Cluster 3)
Different markers corresonding to the same genes in prior slide.

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Genomic Analyses: QTLs, etc.

  • 1.
  • 2.
  • 3. 14L and 14H Lines at 14 and 42 Days (S 14 ) 14L 14H 38 g 319 g 172 g 861 g
  • 4. Life Cycle of Selection Lines
  • 5. QTL Analysis F 2 segregating generations Substantial heterosis or dominance for early growth
  • 6. QTL Analysis F 2 segregating generations Substantial additive variation for late growth
  • 7.
  • 8. RFLP A a AA Aa aa Resulting gel
  • 9. RAPD A a AA Aa aa Resulting gel No PCR product
  • 10. Microsatellite A a AA Aa aa Resulting gel GCC GCC GCC GCC GCC GCC GCC GCC
  • 11. Molecular marker loci properties Rafalski and Tingey, 1993
  • 12.
  • 13. Holliday model of chromosome recombination
  • 14.
  • 15. Backcross design Parental strains X X F 1 strains Backcross Progeny Non-recombinants Recombinants Frequency = 1 - r Frequency = r m q m q M Q M Q m q M Q M Q M Q m q M Q M Q M Q m Q M Q M q M Q
  • 16. Bulked segregant analysis 14L 14H F 1 F 2 Bulk 1 Mostly qq ; enriched for m , depleted for M Bulk 2 Mostly QQ ; enriched for M , depleted for m m q m q M Q M Q M Q m q
  • 17. Recombinant inbred lines (by selfing)
  • 18. Recombinant inbred lines (by sibling mating)
  • 19.
  • 20. Grand-daughter design X Grandsire & Grandam(s) X X Sons x random dams (genotyped) Son Son Grand-daughters M 1 Q 1 M 2 Q 2 M x Q x M x Q x M x Q x M x Q x M 1 Q 1 M x Q x M 2 Q 2 M x Q x M x Q x M x Q x M 1 Q 1 M x Q x M x Q x M x Q x M x Q x M x Q x M 2 Q 2 M x Q x
  • 21. Determining the genome sequence Sequence assembly Partial digest Library of bacterial artificial chromosomes (BACs) with genomic fragments Alignment of BAC clones > contigs and anchoring On the molecular gene map Sequencing of overlapping BAC clone fragments “ Tiling path” > selection of BAC clones to be sequenced Annotation of genome sequence > prediction of genes
  • 22. Genomes of human and mouse compared human: 22 chromosomes + X or Y mouse: 19 chromosomes + X or Y homologous segments are color-coded (total >300) human chromosomes correspond to segments of different mouse chromosomes e.g.. Segments of chr. 10, 11, 15, 16 and 19 correspond to mouse chromosome 7
  • 23. Historical perspective: from genetic map to genome sequence
  • 24. Chicken Chromosome 4 25 cM LEI122 * LEI76 LEI81 ** 270 cM SPP1 Murine SPP1 56.0 cM Chicken Chromosome 4 Murine Chromosome 5 (Late Growth QTL) (Cluster 1) (Cluster 2) Cluster 1 - Protein kinase II, glucokinase, VDR, galactosyltransferase, Ubiquitin C and FGF5 Cluster 2 - Acads, Phkg and Asl Cluster 3 - ZP3, Zonadhesin , Epo and Actin (Cluster 3)
  • 25. Different markers corresonding to the same genes in prior slide.