Whole genome scans to localise QTL

X

Likely position QTL

Chromosome with mapped markers

BAC ContigSpanning QTL

region

New Markers Candidate Genes

Fine Mapping Test by associationUse in MAS

QTL to gene

Sequencing

Identification of putative functional

variations

Zoo-FISH

Solinas-Toldo et al (1995) Genomics 27 489-596

Bovine Control

Hamster Control

Genotyping96 cells in Duplicate

BTA 9Linkage groups

LOD4 6

IBRP 97125.00 cM

USDA 97109.00 cM

RH17.58 Ray

= LOD 3 framework markerDifferent colours are different

frameworks

BTA 9Linkage groups

LOD4 6

IBRP 97125.00 cM

USDA 97109.00 cM

RH17.58 Ray

= LOD 3 framework markerDifferent colours are different

frameworks

Map construction using “CarthaGene”

www.inra.fr/bia/T/CarthaGene/

Comparison of maps using “Anubis”www.roslin.ac.uk/cgi-bin/anubis

BL1022 1001110111100000100001100100001100100000000110001000010000000010000000000001000000000000100000BM1827 1110110111110100000000000000000000100010000010000000010000000010000000010000000100000000000000BM2901 1110110111110100000010000000000000100000010010001000010000000010000001100000000100000000110000BM4028 0000010010001000000000100000000000000000000000001000010000000000000000000000000000000000000000BM6108 1101010111100100100001100001000000100001000000000000110000000000000000000001000000000100100000BM6116 1001010111100100100001100101001110100001000110001000010100000010000000000001000000000000110000BM6122 1101010111100100100101100101001100100001000010000000010100000010000000000001000000000000100000BM6404 1010110111110100000010000000000000100000010000001000010000000010000001100000000100000000010000

Current Roslin WGRH Map

BTA 3

MARC 1997 RH 2002 RH 2004

Lod 4 Lod 6

Roslin INRAUniversity of PaviaDanish Institute of Animal ScienceUniversity of OsloUniversity of PiacenzaUSDA- BARCUSDA- MARCSchool of Veterinary Medicine HanoverUniversity of Alberta

• 1256 Microsatellites• 1402 Genes / ESTs• 282 AFLPs• 3826 SNPs

TOTAL 6766 (June 2005)

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100

120

140

160

180

200

220

240

HSA1

RBAF600 (19)

EIF3S2 (32)

BTA 2

DKFZp547C228 (35)

RE2 (166)

PRKCZ (1)SHARP (16)

VAMP4 (167)

HNRPU (243)

RYR2 (232)LOC199907 (230)

BTA 3

BTA 16

BTA 28

BTA 16

BTA 16

CAPN2 (219)

FH (237)

ENO1 (8)

JAK1 (65)

SSC 6

CLCA1 (87)

HSD17B7 (159)

SSC 4

GLUL (178)

IRF6 (207)

SSC 9

SSC 10ESRG (213)

P5CR2 (223)

HSPA6(SSC9)

Mo 4

PRKCZ (1)

JAK1 (65)

Mo 3

KIAA1365 (70)

NTRK1 (155)

Mo 1

PFX (158)

HNRPU (243)

PRKCZ (1)

JAK1 (65)

Rat 5

KIAA1365 (70)

SH2D2A (155)

Rat 2

Rat 13

PFX(158)

HNRPU (243)

EIF3S2 (32)(Rat 2)

BTA SSC Mouse Rat

RSJW369 (194)(BTA3)

MGC2704 (194)(SSC 1)

GUK1 (224) (SSC 2)HNRPU (243) (SSC 16)RSJW894 (244)

(BTA 7)

Comparativemaps of HSA1 with cow, pig

mouse and rat

0

20

40

60

80

100

120

140

160

180

200

220

240

HSA1

RBAF600 (19)

EIF3S2 (32)

BTA 2

DKFZp547C228 (35)

RE2 (166)

PRKCZ (1)SHARP (16)

VAMP4 (167)

HNRPU (243)

RYR2 (232)LOC199907 (230)

BTA 3

BTA 16

BTA 28

BTA 16

BTA 16

CAPN2 (219)

FH (237)

ENO1 (8)

JAK1 (65)

SSC 6

CLCA1 (87)

HSD17B7 (159)

SSC 4

GLUL (178)

IRF6 (207)

SSC 9

SSC 10ESRG (213)

P5CR2 (223)

HSPA6(SSC9)

Mo 4

PRKCZ (1)

JAK1 (65)

Mo 3

KIAA1365 (70)

NTRK1 (155)

Mo 1

PFX (158)

HNRPU (243)

PRKCZ (1)

JAK1 (65)

Rat 5

KIAA1365 (70)

SH2D2A (155)

Rat 2

Rat 13

PFX(158)

HNRPU (243)

EIF3S2 (32)(Rat 2)

BTA SSC Mouse Rat

RSJW369 (194)(BTA3)

MGC2704 (194)(SSC 1)

GUK1 (224) (SSC 2)HNRPU (243) (SSC 16)RSJW894 (244)

(BTA 7)

In OMIM HSA 65-70MB:30 genes with known phenotypesSeveral with immune or reproductive function RPE65 – retinal pigment ARH1 - Ras proto-oncogene

In OMIM HSA 154-157MB:23 genes with Olfactory function

HSA1 vs Mouse HSA1 vs Rat

Chr 4 Chr 5

Chr 3

Chr 2

Chr 13Chr 1

Bovine genome sequence

Shotgun sequencing • Baylor College of Medicine Genome Centre• Inbred Hereford Bull

– 3x Coverage November 2004• 300,000+ plus sequence contigs

– 6x Coverage June 2005• Some assigned to chromosomes • 2.4 M SNPs

– 8X “Final” Assembly due Easter 2006

Assembling the sequence

} } }Sequence reads assembled into Contigs

Contigs assembled into Scaffolds

Scaffolds assigned and aligned on Chromosomes

Scaffolds containing marker sequences can be aligned with the Map

Sequence assembly

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9

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6

5

4

3

2

1

13

12

11

10

9

8

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6

5

4

3

2

1

Marker Map

Unassigned

Contributions to the Composite map

17,254 distinct markers

ILTX SIAG9190 513 1351 1476 2564

ILTX 3434 520 402 51SIAG 5513 3218 48SIAG-MARC 4881 41

2564

BovGenSIAG-MARC Mizzou

BovGen

Mizzou

• Comparative Alignment of Genomes – Genome Evolution – Explore gene content– Function

• Annotation – in process…