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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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family bovidae
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
sub family caprinae
Sub-family Caprinae
  • Sheep
  • Goats
  • Chamois
  • Musk Ox
  • Ibex
  • Tahr
  • etc
sheep
“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=?
goats
“Goats”
  • Domestic goat (Capra hircus), 2n=60
    • ~100 breeds
  • Mountain goat (Oreamnos americanus), 2n=?
sheep goat and cattle karyotypes
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
sheep goat hybrids and chimaeras
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.)

principles of linkage analysis
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
linkage mapping needs
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
slide10

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
slide11

Ovine CD5 microsatellite

A

C

D

F

G

H

FH

AD

  • direct incorporation of 33P-dATP, denaturing gel electrophoresis
linkage map marker types other
Linkage Map Marker Types - Other
  • SSCP
  • RFLP
  • protein polymorphism
  • VNTR
  • SNP
  • phenotype for Mendelian (single gene) trait
mapping populations for sheep and goats
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
goat mapping herd
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.
goat linkage map
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
international mapping flock imf
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.
slide17

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

x chromosome mapping flock xmf
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.
marc sheep mapping flock
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.
csiro sheep mapping flock
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
numbers of markers typed by groups
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).
status of sheep linkage map
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
comparing the sheep and goat maps
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
slide30

Sheep

Goat

Oxford grids - sheep linkage vs goat linkage

From http://oxgrid.angis.org.au/

slide31

Oxford grids - sheep linkage vs goat linkage

Sheep chr 4

Goat chr 4

From http://oxgrid.angis.org.au/

comparing sheep and goat linkage maps
Comparing sheep and goat linkage maps

pdf files sheep-goat comparisons at rubens.its.unimelb.edu.au/~jillm/jill.htm

sheep and goat mapping data web sites
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
comparing the sheep and cattle linkage maps
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
comparing the sheep and human maps
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
sheep genetic vs human sequence map
Sheep genetic vs human sequence map

Clickable pdf files sheep-human comparisons at rubens.its.unimelb.edu.au/~jillm/jill.htm

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