It   any seer”/ worth noting that eae Ma ease”linkage | ee NEED A A AEdisequilibrium | ‘seexists between the HUMTHO1 micro- satellite ; and ;  NEEDED IDLE EE| minisatellite | 6(cid:24):(cid:1)(cid:4),:(cid:20)(7& which « controls | INS | } gene ¢ - expression | . (Lucassen et (cid:17)(cid:10)!& (cid:31)33/1 - McGinnis sand “Ee a| Spielman, (cid:31)33 7& as ; well ¢ Las | ee &*; between | (cid:24):(cid:1)(cid:4),:(cid:20)( enn MAand t es| the | » Fokl- ((cid:29)%9 “ano> analyzed i in t | the | eeepresent : study | weep DA Aa OO(McGinnis ¢ sand | Spielman, (cid:31)33 7! <(cid:12) \ the « other | r hand, i it    ; been | Oh EEE| proposed t   6(cid:20).>(cid:20)7 _ alleles, \ , Which Lact ¢ |Last a. is regulatory CF EE LIMES: transcription | 1 factors « (cid:11)*   Mn THs — Tt[ gene i © PS>in eee1 vitro, 1 , May « ee LARS/ exert s kA SHO{ some ¢ whe eeng NNO> activity « (on 1 nearby § meio/ genes ee; such ¢ 1 as t ; the | we’ bpee”> INS | ) gene ( » (Meloni « i et (cid:17)(cid:10)!& (cid:31)3327! >(cid:12) Se EEE OOintriguing speculation | FEsuggested | ee eg the above | EEN ELE Oeconsiderations | ~Yeeewand in line “aeog awith | aM| OUF | Ee ERED DEEN' findings meiis | on Sthat 1 o “re./ more | - than « -one | moo”gene | ——— Fee- enclosed : | in | | the 11pls ! region | ) may | exert |  concerted | ee OOaction | on | _ the longevity trait | coeby: _means | (cid:11)*  _ shared | SAP eww ASSregulator, for | ELA YERexample the HUMTHO1 1 microsatellite. | Int yee\ this « feecase, | athe 1 - functional ; EES IE EI EES| interaction | oe| between : 1 stress-response genes and metabolic-pathway “eescontrol genes may have evolved into  Oe EE OEE OEphysically rertight oe EEErelationship, putting ~ pees eh Sy Neemaster-genes  seeas TH, (cid:24):(cid:1)& IGF2 in  small a“ peasepiece (cid:11)* ae 2 Eeegenome where CEESthey « p> peescontrol | i — in =functions | om Ke; which | are | vital | | for a_————oere roe‘development and eae aes| survival, | and | er —| possibly play  my ™role in determining longevity in humans. The knowledge (cid:11)* sy eeeythe — Peentire $:> rey “eMsequence offered by the oO NOHuman pe PREGenome Project will enable us >to check many more ee eeemarkers -  , In | the 1 mw MOMregion | (cid:11)* " interest, | _ possibly | in “MINfull linkage | disequilibrium with - DONE DODD DI IN_ functional variants. | In: | any Tocase, | the 1 results | (cid:11)* pee* the | ee yee: present | | pivotal “orem| study « oe DE EINESencourage | further  investiga- tion | | in | | this | OREN Rs ™intriguing | ‘region | (cid:11)* the | Ma ponhuman | mene eee| genome.

Acknowledgements

-(cid:2) thank . 4(cid:2)**  Leips ; ; and ' | Trudy | (cid:29)!.! . Mackay | for ‘critical « | comments « on | | this 1 ; Manuscript. This | | study» Was | pe eee; supported |  #E((cid:1)(cid:20) NEN DO(Ministry | for | University | and | | Scientific | and ’ fee eee| Tech- EDnological 2 eee reResearch, Italy) Foe”Project o~mMe sa aes‘Genetic EEEDeterminants (cid:11)* ry —~—~Human Longevity’ (cid:30)000(cid:23) (cid:30)00(cid:30)& by. (cid:24):(.> ED IDES(Italian | pp eR AMIN| National | | Research | | Center | “on. | Aging), | by | NIH | Ne| Grant | (cid:26)# D /DD and | — ™| by 3 ~ ayoean | er AN| Ellison | \esseseaseee| Medical | | Foundation | | Grant, | by | Grants - *(cid:21)(cid:11)" fo SI ONE| Italian | | Ministry « (cid:11)* ’ Health, EPProgetti | | Finalizzati | .:( and |  =!.! OE OID OS“Genage” | y,~-_to | .!(cid:29)!

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