1
Mammals with genomes sequenced
Comparative
genomics
15.2. - 16.2.
2001
and few
others (rhesus
macaque, dog, cat,
opossum, armadillo,
platypus, …
5.12.2002
1.4.2004
1.9.2005
2
2
Rat and mouse are relevant models for
human genetics
3
LINDBLAD-TOH K., Nature 428, 475 - 476
RNO20
HSA6
MMU17
Human
(HLA)
Rat
(RT1)
Mouse
(H-2)
4
5
Hurt et al., Genome Research 14:631-639, 2004
Congenic rat strain for MHC (RT1)
Segment of Chr.20
(incl. MHC)
SHR.BN20
6
BN
SHR.BN20
1
2
3
4
5
6 7
8 9 10 11 12 13 14 15 16 17 18 19 20 X Y
SHR
1
2
3
4
5
6 7
8 9 10 11 12 13 14 15 16 17 18 19 20 X Y
SHR.BN20
7
1
2
3
4
5
6 7
8 9 10 11 12 13 14 15 16 17 18 19 20 X Y
TRANSPLANTATION OF THE SKIN
RESULT: permanent graft take
+
Inbred STRAIN A
Inbred STRAIN A
Genotype aa
Genotype aa
SYNGENIC TRANSPLANTATION
8
TRANSPLANTATION OF THE SKIN
RESULT: permanent graft take
+
Inbred STRAIN B
Inbred STRAIN B
Genotype bb
Genotype bb
SYNGENIC TRANSPLANTATION
9
TRANSPLANTATION OF THE SKIN
RESULT: graft rejection
-
Inbred STRAIN A
Inbred STRAIN B
Genotype aa
Genotype bb
ALOGENIC TRANSPLANTATION
10
TRANSPLANTATION OF THE SKIN
RESULT: graft rejection
-
Inbred STRAIN B
Inbred STRAIN A
Genotype bb
Genotype aa
ALOGENIC TRANSPLANTATION
11
TRANSPLANTATION RULES
Inbred
STRAIN A
Inbred
STRAIN B
-
Genotype aa
-
Genotype bb
+
+
F1
Genotype ab
ab x ab
+
+
+
F2
+
+
aa
ab
ab
Genotypes
+
bb
+
+
aa
ab
ab
Genotypes
bb
12
TRANSPLANTATION RULES
Inbred
STRAIN A
Inbred
STRAIN B
-
Genotype aa
-
Genotype bb
+
+
F1
Genotype ab
3
4
+
ab x ab
F2
+
aa
+
ab
-
-
+
ab
Genotypes
bb
3
4
+
aa
+
ab
+
ab
Genotypes
+
bb
13
EXCEPTIONS FROM TRANSPLANTATION RULES I.
Unsuccessful transplantation of the skin from male to female rats within one
inbred strain.
aa
XY
aa
XX
+
aa
XY
+
+
aa
XX
Expression of the male transplantation antigen coded by H-locus on
chromosome Y (immune response anti-H-Y).
14
EXCEPTIONS FROM TRANSPLANTATION RULES II.
Unsuccessful transplantation of the skin from parental strain male to F1 female.
-
P
a a
X Y
F1
a b
X X
Reaction against H-Y antigen
15
EXCEPTIONS FROM TRANSPLANTATION RULES III.
Unsuccessful transplantation of the skin from paternal strain rats to F1 male.
a a
X Y
a a
X X
-
b a
X Y
Response against H-X antigen of strain A
16
EXCEPTIONS FROM TRANSPLANTATION RULES III.
Unsuccessful transplantation of the skin from paternal strain rats to F1 male.
b b
X Y
b b
X X
-
a b
X Y
Response against H-X antigen of strain B
17
HOST vs. GRAFT REACTION
Transplantation of skin, kidney or other organ without lymphoid cells capable
of immune reaction
Graft-take
Graft
genotype
Host
genotype
aa
aa
aa
bb
aa
ab
ab
aa
newborn
+
+
+
+
- graft rejected
adult
+
+
-
Lethally
irradiated
+
+
+
+
+ graft-take
18
GRAFT vs. HOST REACTION
Transplantation of BONE MARROW, LYMPHOCYTES
LETHAL EFFECT (GvHR)
Graft
genotype
Host
genotype
aa
aa
aa
bb
aa
ab
ab
aa
newborn
+
+
- HOST SURVIVES
adult
+
-
Lethally
irradiated
+
+
+ HOST DIES
19
GRAFT vs. HOST REACTION
Transplantation of BONE MARROW, LYMPHOCYTES
LETHAL EFFECT (GvHR)
Graft
genotype
A
B
A
B
aa
bb
aa
bb
Host
genotype
A
B
B
A
aa
bb
bb
aa
newborn
+
+
- HOST SURVIVES
adult
-
Lethally
irradiated
+
+
+ HOST DIES
20
GRAFT vs. HOST REACTION
Transplantation of BONE MARROW, LYMPHOCYTES
LETHAL EFFECT (GvHR)
Graft
genotype
Host
genotype
F1(AxB)
A
F1(AxB)
B
A
ab
ab
B
aa
bb
newborn
adult
Lethally
irradiated
-
-
-
F1(AxB)
+
+
+
F1(AxB)
+
+
+
aa
bb
ab
ab
- HOST SURVIVES
+ HOST DIES
21
GRAFT vs. HOST REACTION
Transplantation of BONE MARROW, LYMPHOCYTES
LETHAL EFFECT (GvHR)
Graft
genotype
F2(AxB)
Host
genotype
F1(AxB)
newborn
adult
Lethally
irradiated
ab
ab
+
-
ba
ab
-
-
-
bb
ab
+
+
+
aa
ab
- HOST SURVIVES
+
-
+
-
+ HOST DIES
22
GRAFT vs. HOST REACTION
Transplantation of BONE MARROW, LYMPHOCYTES
LETHAL EFFECT (GvHR)
Graft
genotype
A
Host
genotype
F2(AxB)
newborn
adult
Lethally
irradiated
aa
-
-
-
aa
ab
+
+
+
aa
ba
+
+
+
aa
bb
+
-
+
aa
- HOST SURVIVES
+ HOST DIES
23
GRAFT vs. HOST REACTION
Transplantation of BONE MARROW, LYMPHOCYTES
LETHAL EFFECT (GvHR)
Graft
genotype
B
Host
genotype
F2(AxB)
newborn
adult
Lethally
irradiated
bb
ab
+
+
bb
ba
+
+
+
bb
bb
-
-
-
bb
aa
- HOST SURVIVES
+
+
+
+ HOST DIES
24