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2 RIKEN Symposium MHC Dynamics and functions of the MHC genes of animals from fish to human- Friday, Apl. 15, :00-17:10 Okochi Hall, RIKEN (The Institute of Physical and Chemical Research) Contact: Retrovirus Research Unit (Tel ) ******************************************************************************** MHC MHC MHC HLA HLA HLA 1, MHC MHC MHC ********************************************************************************

3 1 - (30 ) (20 ) (20 ) Genomic Organizations of the Major Histocompatibility Complex in Cat and Dog (30 ) Naoya Yuhki (National Cancer Institute USA) ( 2 ) MHC ( ) 2 - (15 ) (15 ) (15 ) 3 MHC (25 ) (25 ) (25 ) (25 ) 2

4 4 (20 ) (15 ) 5 (30 ) 1,

5 4

6 Major Histocompatibility Complex MHC HLA Human Leukocyte Antigen T HLA 6 6p Mb HLA HLA-A -B -C I HLA-DR -DQ -DP II HLA I II TNF III HLA HLA 100 MHC HLA HLA paralogous 1q Mb HLA 3.6 Mb HLA 45 ( HLA 70 TNF ) kb HLA 6 HLA 1,400 HLA MHC 1q p13 9q33-34 HLA 1q p13 9q33-34 paralogous HLA 30 kb HLA HLA HLA 100 HLA 5

7 100 kb 30, kb MHC 10 Mb MHC HLA MHC MHC MHC MHC MHC 4 5 MHC 6p21.3 1q p13 9q paralogous 6p21.3 MHC MHC T MHC MHC MHC T adaptive immunity 6

8 MHC (Artiodactyla) MHC MHC Bovine Leukocyte Antigen BoLA 23 BoLA DO DY DM TAP LMP II IIb DR, DQ MHC IIa MHC (OLA) MHC (GoLA) II BoLA II (BLV) BLV T (HTLV) B (EBL) BLV (PL) EBL BoLA-DRB3 BLV BLV BoLA II II EBL 7

9 - - MHC (SLA) SLA SLA SLA SLA DNA SLA SLA INRA Sanger Inst. 2.4 Mb SLA - MHC MHC MHC SLA I SLA I I HLA I MHC SLA SBT PCR-RFLP PCR-SSP SLA I II I α1, α2 SLA I HLA I DNA SLA 5 2 SLA SLA 8

10 Genomic Organizations of the Major Histocompatibility Complex in Cat and Dog NAOYA YUHKI Laboratory of Genomic Diversity, National Cancer Institute at Frederick Abstract: We have established gene organization and a draft sequence of domestic cat MHC, using methods of RH mapping, FISH, BAC/PAC mapping and shotgun sequencing. This study showed that unlike a majority of mammalian MHCs so far studied, the domestic cat MHC has a split genomic structure, one including extended class II, classical class II, class III and proximal class I regions which localize on peri-centromeric region of a long arm of chromosome B2 and other including a distal class I and extended class I regions which localize on a telomeric region of a short arm of the same chromosome B2. Previous comparative study indicated that the cat chromosome B2 was rearranged from the syntenic human chromosome 6 by two chromosome inversions, one including the entire short arm and other including a distal portion of the long arm. Our results support this study and further suggest that a breakpoint of the short arm inversion resides on the MHC. Based on recently established two supercontig sequences for canine MHC assembled in the canine WGS sequencing project, we concluded that canine MHC also has the split gene organization as seen in the domestic cat MHC, however, one segment -extended class II, classical class II, class III and proximal class I regions localizes on chromosome 12 and other -distal class I and extended class I localizes on chromosome 35. Since the split in both feline and canine MHCs were found between TRIM39 and TRIM26 genes, we concluded that this MHC structure occurred as a single event before the split of feline and canine species, was maintained through species evolution and influenced unique gene organization of class I genes in both MHCs. 9

11 Procyon lotor mtdna km MHC PrLA-DRB1 10

12 MHC 9,000 15,500 13,500 5,000 (Major Histocompatibility Complex ; MHC) T MHC MHC MHC DNA MHC II

13 MHC MHC MHC I Ia (Onmy-UBA) Ia α3 α1 α2 18 kbp Ia Ia α1 6 α2 3 α3 3 α1 UBA 5 Ib Onmy-UCA UDA UEA UFA UGA UBA Ia 18 Ib 14 MHC Ι (Ia Ib) Ia MHC I Ia IHN Ia Ia Ib IPN 12

14 MHC MHC T Tcr (Ig) MHC Tcr Ig Tcr Ig MHC MHC Tcr MHC MHC MHC MHC MHC 13

15 MHC genome paralogy MHC MHC MHC MHC MHC VLR (variable lymphocyte receptor) Max Cooper, Zeev Pancer, Chris Amemiya VLR 14

16 β α 15

17 MHC MHC MHC MHC Mb MHC MHC birth and death MHC 16

18 M-integra MHC MHC M-integra MHC ortholog M-integra M-integra web G-compass G-compass H-InvDB G-compass G-compass MHC MHC 17 MHC MHC 17

19 18

20 MHC MHC MHC II MHC MHC FeLV FIV FIP MHC MHC FLA- DRB 2 DNA MHC MHC 19

21

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