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Genetic Maps - with a Presentation of the Differences between Sheep and Goats

Genetic Maps - with a Presentation of the Differences between Sheep and Goats. Jill Maddox. Family Bovidae. 9 sub-families ~140 species in 45 genera ungulates, ruminants found in a wide variety of habitats sheep and goats belong to Caprinae sub-family

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Genetic Maps - with a Presentation of the Differences between Sheep and Goats

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  1. Genetic Maps -with a Presentation of the Differences between Sheep and Goats Jill Maddox

  2. Family Bovidae • 9 sub-families • ~140 species in 45 genera • ungulates, ruminants • found in a wide variety of habitats • sheep and goats belong to Caprinae sub-family • cattle, buffalo, bison belong to Bovinae sub-family • Caprinae and Bovinae diverged ~17 - 20 million years ago • Robertsonian translocations common in many bovid lineages  different chromosome numbers

  3. Sub-family Caprinae • Sheep • Goats • Chamois • Musk Ox • Ibex • Tahr • etc

  4. “Sheep” • All Ovis “species” can interbreed • Domestic Sheep (Ovis aries), 2n=54 • > 200 breeds • European Mouflon sheep (Ovis musimon), 2n=54 • Asiatic Mouflon sheep (Ovis orientalis), 2n=54 • Bighorn sheep (Ovis canadensis), 2n=54 • Dall’s sheep (Ovis (montana) dalli), 2n=54 • Siberian bighorn or Snow sheep (Ovis nivicola), 2n=52 • Giant wild sheep (Ovis ammon), 2n=56 • Oriental steppe or Urial sheep (Ovis vignei), 2n=58 • Barbary sheep or Aoudad (Ammotragus lervia), 2n=? • Blue sheep or Bharals (Pseudois nayaur), 2n=?

  5. “Goats” • Domestic goat (Capra hircus), 2n=60 • ~100 breeds • Mountain goat (Oreamnos americanus), 2n=?

  6. Sheep, Goat and Cattle Karyotypes • Sheep • 2n = 54 • Goat, Cattle • 2n = 60 • 3 centric fusion events account for the differences in chromosome number between sheep vs goats and cattle OAR1 = CHI/BTA 3 + 1, OAR2 = CHI/BTA 8 + 2, OAR3 = CHI/BTA 11 + 5 • Goat resembles sheep chromosomal morphology for OAR 8, 9 and X (CHI 9, 14 and X) rather than cattle

  7. Sheep - Goat Hybrids and Chimaeras Chimaera - Geep Fehilly et al., (1984) Nature307: 634-6. Photo from G.Anderson (Pozin et al., (1987) J Anim Sci65: 325-30. Interspecies Hybrid - Geep Sire - ram, dam - doe Male - 2n = 57 - Botswana Letshwenyo & Kedikilwe (2000) Vet Rec146:732-4. Female - 2n = 57 - NZThis animal was fertile when backcrossed to sheep. (Stewart-Scott et al., (1990) NZ Vet J38: 7-9. Tucker et al., (1989) Animal Genetics20: 179-186.)

  8. Principles of Linkage Analysis A B a b A b a B • Recombination occurs between homologous chromosomes during meiosis • Alleles of loci close together on a chromosome tend to be transmitted together from parent to offspring • Linked loci - recombination fraction is less than 50% • Unlinked loci - recombination fraction equal to 50% • 1 cM (1% recombination) approximates 1 Mb DNA • LOD scores of greater than 3 indicate loci are linked

  9. Linkage Mapping Needs • sufficient animals from suitable pedigrees • an ideal pedigree consists of large 3-generation full-sibling families • when mapping a trait the cross should be between phenotypically divergent animals • a panel of polymorphic markers that span the genome • ideally all markers are highly polymorphic

  10. GATC Linkage Map Marker Types - Microsatellites • markers of choice for gene mapping • tandem repeats of di-, tri-, tetra- or penta- nucleotide sequences • 50,000 - 100,000 / mammalian genome, randomly distributed • most common form is (CA)n • highly polymorphic • PCR based typing • score by size differences

  11. Ovine CD5 microsatellite A C D F G H FH AD • direct incorporation of 33P-dATP, denaturing gel electrophoresis

  12. Linkage Map Marker Types - Other • SSCP • RFLP • protein polymorphism • VNTR • SNP • phenotype for Mendelian (single gene) trait

  13. Mapping Populations for Sheep and Goats • 3 sheep flocks used for genetic map development • CSIRO has also developed a flock • many QTL flocks • 1 goat herd used for genetic map development • mapping also done in other goat populations

  14. Goat Mapping Herd • Developed by INRA France • 12, 2-generation families • 575 goats • Founding goats derived from the Suffolk, Romanov and Rambouillet breeds • Primarily developed to map the Polled Intersex Syndrome (PIS) • Vaiman et al., 1996 Genetics144: 279-305.

  15. Goat Linkage Map • Male map • Cri-MAP • 219 markers 2,300 cM • Vaiman et al., 1996 Genetics144: 279-305. • sufficient to enable localisation of (PIS) to CHI 1 • 307 markers 2,737 cM • Schibler et al., 1998 Genome Research8: 901-915. • 41 goat markers, 49 sheep markers, 217 cattle markers • incomplete coverage - lots of gaps, no X chromosome

  16. International Mapping Flock (IMF) • Developed by AgResearch, New Zealand • Nine, 3-generation, full-sibling families • produced by MOET • 127 sheep including 98 F2 offspring • Maximum of 222 informative meioses • All F2 progeny share a paternal grandsire • Founding sheep derived from the Texel, Coopworth, Perendale, Romney and Merino breeds • Crawford et al., 1995 Genetics140: 703-724.

  17. Pedigree A Pedigree C 1 2 1 128 4 5 4 32 3 33 34 6 44 7 8 9 10 11 12 13 14 15 45 40 35 36 37 38 39 41 42 43 46 Pedigree H 47 108 1 128 Pedigree E 1 2 47 ? 109 33 3 61 110 111 112 113 114 115 116 117 62 63 64 65 66 67 68 70 71 Pedigree I 1 128 18 ? Pedigree B 1 17 18 19 33 119 20 21 120 121 122 124 125 126 127 131 22 23 24 25 26 123 27 28 29 31 130 Pedigree D 1 17 47 48 20 Pedigree G 49 1 91 47 93 92 95 132 50 51 52 53 54 55 56 57 58 59 60 Pedigree F 1 17 4 72 96 97 98 99 100 101 102 103 104 105 106 107 20 73 74 133 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 IMF

  18. X Chromosome Mapping Flock (XMF) • Developed by AgResearch, New Zealand • 14, 3-generation, half-sibling families • 480 sheep • Maximum of 912 informative meioses • Founding sheep derived from the Romney breed • Initially developed to map the Inverdale (FecI) gene • Galloway et al., 1996 Genome Research6: 667-677.

  19. MARC Sheep Mapping Flock • Developed by Meat Animal Research Centre (MARC), USA • 4, 2-generation, half-sibling families • 295 sheep • Maximum of 538 informative meioses • Founding sheep derived from the Suffolk, Romanov and Rambouillet breeds • de Gortari et al., 1998 Mammal Genome9: 204-209.

  20. CSIRO Sheep Mapping Flock • Romney x Merino (Booroola) • 2 Romney rams with translocations:t1 (rob 6;24), t2 (rob 9;10) • all F1 rams and ewes had one of the translocations • the translocations affect the distribution of crossovers in heterozygotes but do not affect the map length of the chromosome (pers comm Ian Franklin) • MOET - full-sibling F2 families - 172 offspring • from 2 sires and 15 dams • also produced back-cross families - 231 offspring

  21. Development of Sheep Linkage Map

  22. Numbers of markers typed by groups • Many of the markers mapped by CAB were developed or provided by other groups (mainly CSIRO, INRA, USDA, AgResearch and Noelle Cockett).

  23. Status of Sheep Linkage Map • the ovine genome spans approximately 3660 cM • autosomes - 3537 cM (sex av), X chromosome - 132 cM (female) • 1231 loci (1277 markers) on the IMF linkage map • additional 20 markers/loci mapped by USDA on MARC flock but not on IMF • 932 anonymous, 287 genes, 12 unidentified ESTs • 1129 microsatellites, 49 RAPDs, 7 proteins, 30 SSCPs, 57 RFLPs, 5 VNTRs • 700 (55%) cattle markers, 531 (42%) sheep markers, 50 (4%) goat markers • 643 markers on the framework map • 627 - autosomes; 16 - X

  24. Distribution and informativeness of markers on SheepMap v4.2 (sex averaged)

  25. Sheep genetic map - framework v 4.2

  26. Comparison of male and female chromosome lengths (SheepMap v4.2)

  27. Comparing the sheep and goat maps • 218 loci in common • generally there is good agreement in placement of markers on equivalent chromosomes • exceptions • OarCP9 OAR 9 CHI 16 sequence >90% identity • OarHH2 OAR 21 CHI 16 cattle agrees with sheep • BM723 OAR 23 CHI 3 cattle agrees with goat • MAF48 OAR X CHI 19 • however lots of inversions in order and relative expansions/contractions of map regions

  28. Relative sizes of chromosomes

  29. Relative numbers of loci on linkage maps

  30. Sheep Goat Oxford grids - sheep linkage vs goat linkage From http://oxgrid.angis.org.au/

  31. Oxford grids - sheep linkage vs goat linkage Sheep chr 4 Goat chr 4 From http://oxgrid.angis.org.au/

  32. Comparing sheep and goat linkage maps pdf files sheep-goat comparisons at rubens.its.unimelb.edu.au/~jillm/jill.htm

  33. Sheep and goat mapping data web sites • Sheep • rubens.its.unimelb.edu.au/~jillm/jill.htm • www.thearkdb.org/browser?species=sheep and mirrors • oxgrid.angis.org.au • www.livestockgenomics.csiro.au/sheep.shtml • www.marc.usda.gov/genome/sheep/sheep.html • Goats • locus.jouy.inra.fr/cgi-bin/lgbc/mapping/common/main.pl?BASE=goat • oxgrid.angis.org.au

  34. Comparing the sheep and cattle linkage maps • 31 sheep-cattle chromosomal combinations • generally there is good agreement in order between the sheep and cattle • some markers map to non-homologous chromosomes • 598 loci have been positioned on both the sheep linkage and cattle linkage maps • Sheep chromosome 9 equivalent to cattle chromosome 14 plus the top of cattle chromosome 9

  35. Sheep Linkage vs Cattle Linkage

  36. Comparing the sheep and human maps • 603 loci have been mapped in both sheep and humans • (includes loci physically mapped in sheep) • > 60 sheep human chromosomal combinations • many of the regions contain rearrangements in order between the sheep and human maps • 11 sheep human chromosomal combinations where loci have been mapped to the sheep physical map but not to the linkage map • 301 loci positioned on both the human sequence map and the sheep linkage map v 4.2 • some sheep genes not present in humans • DYA, DYB, GLYCAM1, GALECTIN-14 etc

  37. Sheep genetic vs human sequence map Clickable pdf files sheep-human comparisons at rubens.its.unimelb.edu.au/~jillm/jill.htm

  38. Sheep Linkage vs Human Sequence

  39. Summary • Sheep and goat genetic maps are highly similar and share many markers • Sheep genetic map better developed than goat genetic map

  40. Meat and Livestock Australia Australian Wool Innovation AgResearch IMF Allan Crawford Ken Dodds and many others CSIRO Ian Franklin Ken Beh Dennis Hulme and many others University of Adelaide Cindy Bottema INRA Daniel Vaiman Edmond Cribiu Laurent Schibler Noelle Cockett Brad Freking Plus all those other people who have contributed to the development of the Sheep Genetic Map Acknowledgments

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