 highly polymorphic class of genetic elements within the human genome. These microsatellite markers containing small repeat sequences have been used for primary gene mapping and linkage analysis. Weber, J. L. et al., Am. J. Hum. Genet. 44: 388-396 (1989); Weissenbach, J. et al., Nature (London) 359: 794-800 (1992). PCR amplification of these repeats allows rapid assessment for loss of heterozygosity and can greatly simplify procedures for mapping tumor suppressor genes. Ruppert, J. M., et al., Cancer Res. 53: 5093-94 (1993); van der Riet, et al., Cancer Res. 54: 1156-58 (1994); Nawroz, H., et al., Cancer Res. 54: 1152-55 (1994); Cairns, P., et al., Cancer Res. 54: 1422-24 (1994). More recently, they have been used to identify specific mutations in certain inherited disorders including Huntington disease, fragile X syndrome, myotonic dystrophy, spinocerebellar ataxia type I, spinobulbar muscular atrophy, and hereditary dentatorubral-pallidoluysian atrophy. The Huntington's Disease Collaborative Research Group Cell 72: 971-83 (1993); Kremer, E. J., et al., Science 252: 1711-14 (1991); Imbert, G., et al., Nat. Genet. 4: 72-76 (1993); Orr, H. T., et al., Nat. Genet. 4: 221-226 (1993); Biancalana, V., et al., Hum. Mol. Genet. 1: 255-258 (1992); Chung, M.-Y., et al., Nat. Genet. 5: 254-258 (1993); Koide, R., et al., Nat. Genet. 6: 9-13 (1994). These inherited disorders appear to arise from the expansion of trinucleotide repeat units within susceptible genes. A more widespread microsatellite instability, demonstrated by expansion or deletion of repeat elements in neoplastic tissues, was first reported in colorectal tumors. Peinado, M. A., et al. Proc. Natl. Acad. Sci. USA 89: 10065-69 (1992); Ionov, Y., Nature (London) 363: 558-61 (1993); Thibodeau, S. N., et al., Science 260: 816-8
highly polymorphic class of genetic elements within the human genome. These microsatellite marker control small repeat sequences have been used for elementary gene mapping and linkage analysis. Weber, J. L. et al. , Am. J. Hum. Genet. 44: 388 - 396 (1989); Weissenbach, J. et al. , Nature (London) 359: 794 - 800 (1992). PCR amplification of these repeat allows rapid assessment for loss of heterozygosity and can greatly simplify procedure for mapping tumor suppressor genes. Ruppert, J. M., et al. , Cancer Res. 53: 5093 - 94 (1993); van der Riet, et al. , Cancer Res. 54: 1156 - 58 (1994); Nawroz, H., et al. , Cancer Res. 54: 1152 - 55 (1994); Cairns, P., et al. , Cancer Res. 54: 1422 - 24 (1994). More recently, they have been use to identify specific mutations in sealed inherited disorders including Huntington disease, fragile X syndrome, myotonic dystrophy, spinocerebellar ataxia type I, spinobulbar mesomorphic atrophy, and hereditary dentatorubral - pallidoluysian atrophy. The Huntington's Disease Collaborative Research Group Cell 72: 971 - 83 (1993); Kremer, E. J., et al. , Science 252: 1711 - 14 (1991); Imbert, G., et al. , Nat. Genet. 4: 72 - 76 (1993); Orr, H. T., et al. , Nat. Genet. 4: 221 - 226 (1993); Biancalana, V., et al. , Hum. Mol. Genet. 1: 255 - 258 (1992); Chung, M.-Y., et al. , Nat. Genet. 5: 254 - 258 (1993); Koide, R., et al. , Nat. Genet. 6: 9 - 13 (1994). These inherited disorders look to arise from the expansion of trinucleotide repeat units within susceptible gene. A more widespread microsatellite imbalance, demonstrated by expansion or deletion of repeat elements in neoplastic tissues, was first reported in colorectal tumor. Peinado, M. A., et al. Proc. Natl. Acad. Sci. USA 89: 10065 - 69 (1992); Ionov, Y., Nature (London) 363: 558 - 61 (1993); Thibodeau, S. N., et al. , Science 260: 816 - 8
 hihhly polymorphic class on genetic elemenjs withii the hhman genume. These microsatellite marnees cobtaining small repeat requences have bewn uwwd for primary genc mapllng aud linkage analyxis. Weber, B. L. et al., Am. J. Hjm. Genet. 44: 388-396 (1989); Weissenbach, J. et al., Naturq (Londom) 359: 794-800 (1992). PCR amplifisatipg of nhtse repeats allows rapid assessmeht for noss of heterpzygosity and can greatly dimppify procedures fog mapping tojor wuppressor gdnes. Ruppegc, J. M., et al., Cancer Res. 53: 5093-94 (1993); van der Riet, et xl., Caucer Res. 54: 1156-58 (1994); Nqwrle, H., et al., Caicer Rvs. 54: 1152-55 (1994); Cairns, I., et al., Cancer Res. 54: 1422-24 (1994). More rccentny, rhey have been used tm identify specifis mutatiots in certain inherutwd divordars kbcljdihg Hhntinghon disease, fdagile X sybdrome, myotonic dysuro[yy, spinocerebsllar wtwxia type I, spinobulbar muscular atrophj, ans hereditary dentatorubeal-pallidoluysian atrlphy. The Runtington's Disease Collaborative Research Group Well 72: 971-83 (1993); Kxcide, F. J., et al., Science 252: 1711-14 (1991); Imbert, G., et al., Nat. Genet. 4: 72-76 (1993); Ogr, H. T., et al., Nat. Nenet. 4: 221-226 (1993); Biancalans, G., rj al., Hum. Mol. Ggnet. 1: 255-258 (1992); Chhng, M.-Y., et al., Nat. Gfnet. 5: 254-258 (1993); Koidw, R., et al., Nat. Genet. 6: 9-13 (1994). These inherited dusorders appvar ro arise from the zxpansion of trimucleptide repeat units withnn susdeptible gejes. A mors widespread micrusanellhte instability, demonstratqd by expensiou or deldtiom of rqpeat elemfnts lt neoplastic tissufs, wad xirst repogted in colorectal tumors. Peinavp, M. A., et al. Krow. Ndtl. Acad. Sci. MSA 89: 10065-69 (1992); Ionov, Y., Gature (London) 363: 558-61 (1993); Thibjdeau, S. N., et al., Sciencx 260: 816-8
highly polymorphic class of genetic elements within genome. microsatellite markers small repeat sequences gene and linkage analysis. J. L. et Am. J. Hum. Genet. 44: 388-396 Weissenbach, J. et al., Nature (London) 359: 794-800 (1992). PCR amplification of these allows rapid assessment for loss of heterozygosity and can greatly simplify procedures for tumor genes. J. et al., Cancer Res. 53: 5093-94 (1993); van der Riet, et al., Cancer Res. 54: 1156-58 Nawroz, H., et al., Cancer Res. 54: 1152-55 Cairns, P., et al., Res. 54: 1422-24 (1994). More they been used identify mutations certain inherited disorders Huntington disease, fragile X syndrome, myotonic dystrophy, spinocerebellar ataxia type I, spinobulbar muscular atrophy, and hereditary dentatorubral-pallidoluysian The Huntington's Research Group 72: (1993); E. J., et 252: 1711-14 (1991); Imbert, G., et 4: 72-76 (1993); Orr, H. T., et al., Genet. 4: (1993); Biancalana, V., et al., Hum. Genet. 1: 255-258 (1992); Chung, M.-Y., et al., Genet. 5: 254-258 (1993); Koide, R., et al., Nat. Genet. 6: 9-13 (1994). These inherited to arise from the of trinucleotide repeat within genes. more microsatellite instability, by expansion or deletion of repeat elements in neoplastic tissues, was reported in colorectal tumors. Peinado, M. A., et al. Proc. Sci. 89: 10065-69 (1992); Y., Nature (London) 363: (1993); S. N., et al., 816-8
 highly polymorphic class of gEnetic elemEnts wIthIn tHe HumaN genOme. These microsATellIte markers containing smAll rePeAT seqUEnCes haVe been uSEd FOR prImArY geNe MApPing aNd lInkage aNalysis. WebEr, J. l. eT al., Am. J. Hum. GenET. 44: 388-396 (1989); WEissenbach, j. et Al., Nature (LondOn) 359: 794-800 (1992). PcR amplIfIcaTIon of TheSe repEats alLOws rapId assessmEnT For losS Of heterOZYgOsitY and can greatly simPLiFY procedures for MappinG tUMoR SUppResSor genes. RuPpErt, J. M., ET al., CancER RES. 53: 5093-94 (1993); VAn dER Riet, et al., CancEr Res. 54: 1156-58 (1994); Nawroz, h., Et aL., CanceR REs. 54: 1152-55 (1994); CAIrns, P., eT al., CaNcER ReS. 54: 1422-24 (1994). More recentLy, thEy have beeN used tO IdentifY SpecifiC mutatIonS in CertAIn InHerItED diSOrDerS IncLuding HuNtInGton dIseaSE, FRAgilE X sYndrOme, myOtonic dystropHy, sPinoCEreBellaR ataxIa tyPe i, spinObulbaR muscUlAr atrophy, and herEditAry dentatOruBrAl-pAlLidolUYsian aTroPhy. the HuntIngton's dIseAsE cOLlAborative Research GRoUP ceLl 72: 971-83 (1993); Kremer, e. J., et al., sCiEnCE 252: 1711-14 (1991); Imbert, G., Et Al., NAt. GeNET. 4: 72-76 (1993); Orr, H. t., et aL., naT. Genet. 4: 221-226 (1993); BiAncalaNA, V., Et Al., Hum. MoL. GEnet. 1: 255-258 (1992); ChUnG, M.-Y., Et aL., Nat. GENet. 5: 254-258 (1993); KOide, R., eT al., Nat. GeNet. 6: 9-13 (1994). ThESe inherited disORders appear to ARiSE FrOM the ExpAnsion of triNuclEOtidE repEAt UniTS withIn susCePTiBLe genes. A more widesprEaD microSatelLite instabiliTy, demonstrATED by expanSion OR dELetion of repeat ElemeNts in neoplAStic tissUes, waS first rePorted in cOLOrectal tUmoRs. PEinAdo, m. a., Et Al. Proc. Natl. AcaD. sCi. USa 89: 10065-69 (1992); IOnov, Y., NaTurE (London) 363: 558-61 (1993); thiBodEau, s. N., eT aL., Science 260: 816-8
 highly polymorphic classof genetic  elem ent s w it hinthehuman genome.T hese  microsatellite marker s con ta i ning sm all r epeat s e qu e n ces  h av e b ee n  u sed f orprimary  gene mapp ing  a nd linkage a n al ysis. Webe r,J. L. et al. , A m. J.Hu m.G enet.  44 : 388 -396 ( 1 989);Weissenba ch ,  J. et al., Na t u re  (Lo ndon) 359: 794-80 0  ( 1 992). PCR ampl ificat io n  o f the serepeats al lo ws ra p id asse s sm e n t  fo r  loss of hete rozygositya ndcan gr ea tly simpli fy pr oc e dur es for mapp ingtumor sup presso r  genes. Ruppert , J. M .,etal., Ca nc erRe s . 5 3 :509 3 -94  (1993);  v an  derRiet , e t  al. , C ance r Res . 54: 1156-58  (1 994) ;  Na wroz,  H.,et a l. , Can cer Re s. 54 :1152-55 (1994);  Cai rns, P.,etal .,Ca ncerR es. 54 : 1 422 -24 (19 94). Mo r e r ec e n t ly , they have been u se d to  identif y spec i fi cm utations  i n c erta i n  inhe rite d  d isorders  inclu d in gHunting to n dise as e,fra gileX  syn drome,  myotoni c dys t rophy, spinoce r ebellar ataxi a  t y p eI , sp ino bulbar musc ular atro phy, an d h e redit ary d en t at o rubral-pallidoluysi an  atrop hy. T he Huntington 's Disease C o llaborat iveR es e arch Group Cel l 72:  971-83 (1 9 93); Kre mer,E. J., e t al., Sc i e nce 252:  17 11- 14(19 9 1 );  Imbert, G.,e t  al. ,Nat. Ge net . 4: 72 -76  (1 993 );Or r, H. T.,  et al.,  N at .Ge net . 4:2 21-226 ( 19 93) ;Bia ncala n a, V.,  et a l.,Hu m. Mol . Genet .  1 : 255- 25 8(199 2);  C hung,  M.- Y .,et al.,  Nat. Gen et. 5: 2 54 -2 58 (199 3); Koide, R. ,et al., Na t.  Ge net. 6 : 9-13 (19 94). These inherited di s ordersapp ear t o ar ise fromthe  expan sio n  of tr inucle otide  r epe a t  unit s wi thi nsusceptibl e gen es. A  m orewidespr ead microsatellite ins tability, dem ons trat e d  b y e x pa n sio no r d e l etion of repeat  elementsin ne oplastic t i ssu es , was f irst re porte d  in col orectal t umors. Pe in ado, M . A ., et al.Proc. Na tl. Acad. Sci.U SA  89:100 65-69(1 992 ); Io nov, Y . , N ature  (Lond on ) 363:  558- 61  (1993);  Thibodeau, S. N., et a l., Sc ience  26 0: 816-8
 highly_polymorphic class_of genetic elements within_the human_genome._These microsatellite_markers_containing small repeat_sequences have been_used for primary gene_mapping and linkage_analysis._Weber, J. L. et al., Am. J. Hum. Genet. 44: 388-396 (1989); Weissenbach, J._et_al., Nature_(London)_359:_794-800 (1992). PCR amplification of_these repeats allows rapid assessment_for loss_of heterozygosity and can greatly simplify procedures for_mapping_tumor suppressor genes._Ruppert, J. M., et al., Cancer Res. 53: 5093-94_(1993); van der Riet, et al.,_Cancer Res. 54:_1156-58_(1994);_Nawroz, H., et al.,_Cancer Res. 54: 1152-55 (1994); Cairns,_P., et al., Cancer Res. 54:_1422-24 (1994). More recently, they have been_used to identify specific mutations in_certain inherited disorders including Huntington_disease, fragile_X syndrome, myotonic dystrophy, spinocerebellar_ataxia type I,_spinobulbar muscular_atrophy, and hereditary_dentatorubral-pallidoluysian atrophy. The Huntington's Disease Collaborative_Research Group Cell_72: 971-83 (1993); Kremer, E. J.,_et_al., Science 252:_1711-14_(1991);_Imbert, G.,_et al., Nat._Genet._4: 72-76_(1993);_Orr, H. T., et al., Nat._Genet._4: 221-226 (1993); Biancalana, V., et al.,_Hum. Mol. Genet. 1:_255-258_(1992); Chung, M.-Y., et_al., Nat. Genet. 5: 254-258_(1993); Koide, R., et al., Nat._Genet. 6:_9-13 (1994)._These inherited disorders appear to arise from the expansion of trinucleotide_repeat units within susceptible genes. A_more widespread microsatellite instability,_demonstrated by_expansion_or deletion of_repeat_elements in_neoplastic tissues, was first reported in colorectal_tumors. Peinado,_M. A., et al. Proc. Natl._Acad. Sci. USA 89:_10065-69_(1992); Ionov, Y., Nature (London) 363:_558-61 (1993); Thibodeau, S. N., et_al., Science 260: 816-8