MPL

2. 301 350 Schizo-cDNA ---------- --------t- ----gg--t- ---------a --a------- HS307 ----t----- ---------- ---------- ---------- ---------- HS408 ---------- ---------- --------c- -----t---- ---------- SINE-RC2 ---------- ---------- ---------- ---------- ---------- SINE-R11 ---------- ---------- ---------- ---------- ---------- SINE-R14 -----a---- ---------- -------t-- ---------- ---------- SINE-R19 ---------- ---------- ---------- --------c- ---------- FMR-1 --------at ---------- --------t- ---------- ---------- Consensus CTCAAGTACC CAGGGACACA AACACTGCGG AAGGCCGCAG GGTCCTCTGC 351 400 Schizo-cDNA ---------- ---------- ------tg-- ---------- ------tt-- HS307 ---------- ------t--- ---------- ---------- ----c----- HS408 ---------- ---------- ---------- ---------- --t------- SINE-RC2 ---------- ---------- ---------- ---------- ---------- SINE-R11 ---------- ---------- ---------- ---------- ---------- SINE-R14 ---------- ---------- -------a-- ---------- ---------- SINE-R19 ---------- ---------g ---------- ---------- ---t------ FMR-1 ---------- ---------- ---------- ---------- ---------- Consensus CTAGGAAAAC CAGAGACCTT TGTTCACTTG TTTATCTGCT GACCTTCCCT 401 439 Schizo-cDNA --------a- ---------- -----c---- ------cc- HS307 ---t------ ---------- ---------- -------c- HS408 ---------- ---------- ---------- -------c- SINE-RC2 ---------- ---g------ ---------- -------t- SINE-R11 ---------- ---------- ---------- -------t- SINE-R14 ---------- ---------- ---------- ------ct- SINE-R19 ----g----- --------a- -a-------- -------c- FMR-1 ---------- --c------- ---------- -------t- Consensus CCACTATTGT CCTATGACCC TGCCAAATCC CCCTCTG-G HERV-K10 456 151 200 Schizo-cDNA a------a-- ---------- ----cc---- ---------- ---------- HS307 -----g---- ---------- ---------- ---------- ---------- HS408 a------a-- ---------- ---------- ---------- a--------- SINE-RC2 ----gg---- ---------- ---------- ---------- --------a- SINE-R11 ---------- ---------- ---------- ---------- ---------- SINE-R14 a------a-- ---------- ----c----- ---------- ---------- SINE-R19 ---------- ---------- ----g----- g--------- ---------- FMR-1 -----g---- ---g------ ---------- ---------- ---------- Consensus GATCTATGAC CTTACCCCCA ACCCTGTGCT CTCTGAAACA TGTGCTGTGT 201 250 Schizo-cDNA -a-------- ---------- ---------- ---------- ---------- HS307 ---------- ---------- ---------- ---------- ---------- HS408 ---------- ---------- ---------- ---------- ---------- SINE-RC2 ---------- --g------- ----a----- ---------- ---------- SINE-R11 ---------- ---------- ---------- ---------- ---------- SINE-R14 ---------- -----at--- ---------- ---------- ---------- SINE-R19 ---------- ---------- ---------- ---------- ---------- FMR-1 ---------- ---------- ---------- ---------- ---------- Consensus CCACTCAGGG TTAAATGGAT TAAGGGCGGT GCAAGATGTG CTTTGTTAAA 251 300 Schizo-cDNA ---------- ---a------ ----c----- ---------- ---------- HS307 ---------- ---------- ----c----- ---------- ---------- HS408 ---------- ---------- ----a----- ---------- ---------- SINE-RC2 ---------- ---------- ----c----- ---------- ---------- SINE-R11 ---------- ---------- ----g----- ---------- ---------- SINE-R14 ---------- ---------- ----g----- ---------- ---------- SINE-R19 ---------- ---------- --a-t----- ----c----- ---------- FMR-1 ---------- ---------- ----g----- ---------- -a-------- Consensus CAGATGCTTG AAGGCAGCAT GCTC-TTAAG AGTCATCACC ACTCCCTAAT 1 50 Schizo-cDNA ---------- ---c---a-- ---a------ --t------- -----aa--- HS307 ------t--- ---g----g- ---------- --g------- ---------- HS408 -----a---- ---c--g--- -g-------- --t------- ggg---g--- SINE-RC2 ---------- ---g------ ---------- --g------- ---------- SINE-R11 ---------- ---g------ ---a------ --g------- ---------- SINE-R14 ---------- ---c------ ---------- --t------- g----gg--- SINE-R19 ---------- ---c------ ---a--t--- --t------- ------ac-- FMR-1 -----a-c-- ---g--g--- -----c---- --g------- -gg------- Consensus ATGGCGGTTT TGT-GAATAG AAAGGGGGGA AA-GTGGGGA AAAGATTGAG 51 100 Schizo-cDNA -g---a---t ---a---c-- ---------- ---------- --a------. HS307 ---a-g---g -----c---- ---------- ---------- -------t-- HS408 -gg--a---t ---------- ---------g g--------- --a---t--. SINE-RC2 -----g---g -----c---- ---------- ---g------ c--------- SINE-R11 -----g---g ---------- ---------- ---------- ---------- SINE-R14 -g---g-t-t ---a------ ------g--- g--g------ --ta-----. SINE-R19 -----a---a ---------- ---------- ---------- --a--g--t. FMR-1 --g--a---a -----c---- ------g--- g--------- ---------- Consensus AAATC-GAT- GTTGCTGTGT CTGTGTAGAA AGAAGTAGAC ATGGGAGACT 101 150 Schizo-cDNA .-c------- ---------- ---------- ---------- ----g----- HS307 --t------- ---------- ---------- -------g-- ----c----g HS408 .-c------- ---------- ---------- ---------- ----g----- SINE-RC2 --t------- ---------- ---------- ---------- ----c----- SINE-R11 --t------- ---------- ---------- ----t----- ----c----- SINE-R14 .-c------- ---------- g--------- ---------- ----g----- SINE-R19 .-c------- ---------- ---------- ---------- ----g----- FMR-1 --t------- -----c---g g--g------ c--------- ----c----- Consensus TT-CATTTTG TTCTGTACTA AGAAAAATTC TTCTGCCTTG GGAT-CTGTT XY7-sY26 sY34A-XY4 1000 HERV-K18 IDDMK1,2-22 HS307 SINE-R14 HS408 439 HS408 FMR-1 217 SINE-R11 992 779 SINE-R.C2 635 HS307 948 SINE-R19 Schizo cDNA REFERENCES CONCLUSION 1 2 3 4 5 6 7 8 1. Schizo-cDNA - 2. HS307 89.7 - 3. HS408 91.5 91.3 - 4. SINE-R.C2 90.2 95.9 91.8 - 5. SINE-R11 92.0 96.4 93.4 97.3 - 6. SINE-R14 92.0 90.8 93.1 92.2 93.6 - 7. SINE-R19 91.1 92.0 92.0 92.4 94.5 91.1 - 8. FMR-1 87.6 92.3 92.0 93.2 94.1 90.2 89.9 - Fig. 6. Sequence alignments of the SINE-R retroposon family with HS307, HS408, and schizophrenic brain cDNA Fig. 5. PCR analysis of YAC clones in human Xq21.3 region Table 1. Percentage similarity of SINE-R elements Fig. 7. Phylogenetic tree of the SINE-R retroposon family and HERV-K family by neighbour-joining method • Crow TJ. 1984. A re-evaluation of the viral hypothesis: is psychosis the result of retroviral integration at a site close to the cerebral dominance gene. Br J Psychiatry 145:243-253 • Laval SH, Dann J, Burtler RJ, Loftus J, Rue J, Leask SJ, Bass N, Comazzi M, Vita A, Nanko S, Shaw S, Peterson P, Shields G, Smith AB, Stewart J, DeLisi LE, Crow TJ. 1998. Evidence for linkage to psychosis and cerebral asymmetry (relative hand skill) on the X chromosome. Am J Med Genet (Neuropsychiatr Genet) 81:420-427 • Kobayashi K, Nakahori Y, Miyaki M, et al. 1998. An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Nature 394:388-392 • Within the Xq21.3 region, we found two retroposons,HS307and HS408, with a high degree of sequence homology to but not identity with the schizophrenic brain cDNA. • The phylogeny suggests that the HS307sequence could be very closely related to SINE-R.C2 that is human specific retroposon in human genome. • TheHS307and SINE-R.C2 showed similar sequences that caused Fukuyama-type muscular dystrophy. • Therefore, this class of retroposons, as agents of change in the human genome, has potential relevance to pathology. MPL MPL