55,[994 Tmmuno- INNatUo cerlrNIC [ genetics Vet 4g Spnnger- 1994 PL and cosmid clones define the organization of 280 kb of the mouse H-2 complex containing the Cps-I and Hsp7o loci David Sternberg?, James  Pierce? Audrey Goldner-Sauvel, Gasser! , Nat Hongshu Fengl Asifa K. Haql Thomas Sples ' , Clay ton Huntt, Kenneth H. Buetows David D). Chapling Cieretics, University Deirnicn Schod Mcdicine, 422 Curie Boulevard Fcnuvvinin Fhiladelphiz, PA 1910:, USA DuPont Mcrck Phurmcculical Company; Gieuolden Lahontones. SUO South Ridcetdy Vrdloey: Divisicn Glcnolden, FA 19036 , USA Ayci: Tmo: Dana-Farbet Canccr Insttuce Echcol Hinvand Nedical Sucet, Winnar Bosiol, MA 02145. USA Radialogy; Washington MMallincrodi Institute Urversity School of Medicinc Forcl Pak Bailevard, SL. Louis, MO 63R08, USA Fox Chase Cancer Ccucd; Philad-Iphia, PA [911,USA Wui Rurkolnc Arenuc Horrud Fuebos Mcdical [nstitue and Department of Intemel Medicinc; Washingtor: Unitensity School Medizinc, 4939 Aud_t = AFIL? . St_ Louis 63110,USA Rereived Jutie 22, 1993 Abstract: 280 kilobase (kb) contig was isolated Fcou 11 19896}, [UInor (actor and B: (Spies JccrCS gCnoiie P[and cosmic   libraries, MICTSC using a. 1986), and _ number of additional genes designated prohes human cDNA and gcnomic DNA fragmients that BAT} through RAT9 (HLA-B associated MJP the interval betwecn the sccona transcripls: conpwncnt f Spics 989) Or GI-GlO (Sargent al. 1989 complement and Wmor necrosis Jactor genes of thc Although most Of Ile: mouse MHC has beet cloied b; HLA complex Thc cloue demonstrates config synteny chrumosoie walking USIC cosmid vectors (Steininct? eleven molSe homologous genes thai Je cal. 1982a, b; Gcodenow cal 1982; Chaplin genes mapped within the humar major histocompati ualiv "# 198}; Fisher ei al. 1985; Flavell Sepha ! al. 1986; bility compiex. Thesc include the mouse homologs of 1986) , much of thc region between H-2S ani H-2D) BATZ (KLA-B-associaled also three-AsSP atcclateasccipe through BAT9 Which is homologous t0 the HLA region cited abve; and Five genes- clones has "Ot yer been isolated in tnolecular clonas. of 240 TIi: TOr contig kb that spans frumn BATY through region partcular interest hecausc Ile geras CO1 - BAT3. Twelve cosmid clones trolling arranged iri three several phenotypic traits appear t0 Iap within EOn- lgs that contirmi mOst of the structure of tfe PL cortig genc thataflects the antibody resporse [0 TNP Fi- homoloz; and link: RAT} MOuSO t0 the BAT2 ho coll (Shapiro e al,. 1985}. the locus that contzols molog  epproxiiately 15 kb farlher  telomeric. Poly - hemalopoietic histocornpatibilily antigen, Hiv-} (Daley DKA morphic MafkCrs within the cloned region were [987). gcnc that affects susceptibility Io coti map the clcft palale  susceptibility- usC4 (Cps-!) sone-Induced cleft palate , Cps- (Gasset locus i988). the Interval between Hsp70 and BAT6 (valyl- AEd gene Lhz: aflects Susceplibility t0 expetimental tRNA syntherase). This   refines   thc [ocation   of  thc autoitnmunc   orchitis, Orch-} (Teuschcr ct a. Cps-= locus t0 990: 45 kb region contained in the H2-124 Snock = elal. 1993}, have all been localizcd t0 Ihis Mler PL insert. val The isolation ol this porlion of the [Ouse [-2 coriplex in molccular clones will facilitate the identli functionally defincd genes Clozing of eation of Ihcse thts region Ofthe MOusc will also pezmit compatison of Introducliun the slncture this portion of the human and mouse MHCs to defin? the exlent which pecn has evolu- The portion human of the tozarily conservcd. In this study, we havc cloned the major  histocompatibility complex (MHC) that extends fOm the MHC class Iil reglon sutrounding the Hsp70 loci and used po ymor- coinple Tent genes telomeric t0 the phisms in this rcgion to rcfitc Ile location of thz Cps-! class gcne HLA-B is nolable for its extremely high density of furctional locux gcnes (Trowsdale al. 1991). This region has heen using analyzed clones. ovetlapping cosmid and founa duplicated locus ercoding Hsp70 to comain (Sargent Halerials and mcthods Kroriar Txo cosmd Cosmi dlonet libraries wcre CorstUctcu Corr [NIAA Gieerr high relativ? molecular m2ss DNA Punfied fromt USIUE MOFC-321 50725010
55,[994 INNatUo cerlrNIC [ Tmmuno- genetics Spnnger- Vet 4g 1994 PL and cosmid clones define the organization of 280 kb of the mouse H-2 complex containing the Cps-I and Hsp7o loci David Gasser! , Nat Sternberg?, James  Pierce? Audrey Goldner-Sauvel, Asifa K. Haql Thomas Sples ' , Clay Hongshu Fengl ton Huntt, Kenneth H. Buetows David D). Chapling Deirnicn Cieretics, University Fcnuvvinin Schod Mcdicine, 422 Curie Boulevard DuPont Mcrck Phurmcculical Company; Gieuolden Lahontones. SUO South Fhiladelphiz, PA 1910:, USA Divisicn Tmo: Vrdloey: Ridcetdy Dana-Farbet Canccr Insttuce Ayci: Hinvand Nedical Glcnolden, FA 19036 , USA MMallincrodi Institute Echcol Radialogy; Washington Winnar Sucet, Urversity School of Medicinc Bosiol, MA 02145. USA Fox Chase Cancer Ccucd; Wui Rurkolnc Arenuc Philad-Iphia, PA [911,USA Forcl Pak Bailevard, SL. Louis, MO 63R08, USA Horrud Fuebos Mcdical [nstitue and Department of Intemel Medicinc; Washingtor: Unitensity School AFIL? . St_ Louis 63110,USA Medizinc, 4939 Aud_t = Rereived Jutie 22, 1993 Abstract: 280 kilobase (kb) contig was isolated Fcou MICTSC 11 19896}, [UInor JccrCS (actor gCnoiie P[and cosmic   libraries, and B: (Spies using a. 1986), and _ prohes human cDNA and number of additional genes designated gcnomic DNA fragmients that MJP the interval betwecn the sccona BAT} through RAT9 (HLA-B associated conpwncnt f transcripls: Spics complement and Wmor 989) Or GI-GlO (Sargent al. 1989 necrosis Jactor genes of thc Although HLA complex Thc cloue demonstrates most Of Ile: mouse MHC has beet cloied b; config synteny eleven molSe chrumosoie walking USIC genes thai Je cosmid vectors (Steininct? homologous genes ualiv cal. 1982a, b; Gcodenow cal 1982; Chaplin mapped within the humar major histocompati "# 198}; Fisher ei al. 1985; Flavell bility compiex. Thesc include the mouse al. 1986; homologs of Sepha ! 1986) , BATZ (KLA-B-associaled much of thc region between H-2S ani H-2D) and also three-AsSP atcclateasccipe through BAT9 Which is homologous t0 the HLA region cited abve; genes- Five TOr clones contig of 240 has "Ot yer been isolated in tnolecular clonas. kb that spans frumn BATY through TIi: BAT3. Twelve cosmid clones region three partcular interest hecausc Ile geras CO1 - arranged iri EOn- trolling lgs that contirmi mOst of the several phenotypic traits appear t0 Iap within structure of tfe PL cortig and link: MOuSO RAT} homoloz; genc thataflects the antibody resporse [0 TNP Fi- t0 the BAT2 ho coll (Shapiro e al,. 1985}. the locus that contzols molog  epproxiiately 15 kb farlher  telomeric. Poly - DKA hemalopoietic morphic histocornpatibilily antigen, Hiv-} (Daley MafkCrs within the cloned region were usC4 [987). map the clcft palale  susceptibility- gcnc that affects susceptibility Io coti (Cps-!) locus sone-Induced cleft palate , the Interval between Hsp70 Cps- (Gasset and BAT6 (valyl- i988). AEd tRNA syntherase). This   refines   thc gene Lhz: aflects Susceplibility t0 expetimental [ocation   of  thc Cps-= locus t0 autoitnmunc   orchitis, Orch-} 45 kb region contained in the H2-124 (Teuschcr ct a. 990: Snock = PL insert. elal. 1993}, have all been localizcd t0 Ihis Mler val The isolation ol this porlion of the [Ouse [-2 coriplex in molccular clones will facilitate the identli eation of Ihcse functionally defincd genes Clozing of thts region Ofthe MOusc will also pezmit compatison of Introducliun the slncture this portion of the human and mouse MHCs to defin? the exlent which The portion has pecn of the evolu- human major  histocompatibility tozarily conservcd. In this study, we havc cloned the complex (MHC) that extends fOm the MHC class Iil reglon sutrounding the Hsp70 loci and used po ymor- coinple Tent genes telomeric t0 the class gcne HLA-B phisms in this rcgion to rcfitc Ile location of thz Cps-! is nolable for its extremely high density of furctional locux gcnes (Trowsdale al. 1991). This region has heen analyzed using ovetlapping cosmid clones. and founa to comain duplicated locus ercoding Hsp70 (Sargent Halerials and mcthods Kroriar Cosmi dlonet Txo cosmd libraries wcre CorstUctcu USIUE high relativ? molecular m2ss DNA Punfied fromt MOFC-321 Corr [NIAA Gieerr 50725010