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Mapping of Monogenic Traits

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Mapping of Monogenic Traits Stellingen: Behorendebi j het proefschrift Analysiso fth echicke ngenome :mappin go fmonogeni ctrait s 1. Het ontwikkelen van microsatelietmerkers uit cDNA sequenties is een goede manier omtegelijkertij d een bijdrage te ieverenaa nzowe l de genetische koppelingskaart als devergelijkend e genenkaart. Ditproefschrift 2. Bulkedsegregan tanalys eme tbehul pva nfluorescerend e microsatelietmerkers, is een betrouwbare methodeo md egenetisch e locatie van enkelvoudige kenmerkenefficien t meet ebepalen . Ditproefschrift 3 Terwijl bulked segregant analyse metbehul p van fluorescerende microsatelietmerkers totee naanzienlijk ekostenbeparin g leidt invergelijkin g met eenstudi ewaarbi j nakomelingenindividuee lgetypeer dworden , gaat dit niette n kosteva nd egenetisch e afstandwaaro pgekoppeld e merkers gevonden zullen worden. Ditproefschrift 4. Doordatd egenome nva nmen se nki p ondanks hungrat e evolutionaire afstand zoveelgeconserveerd egebiede nvertonen ,kunne nvergelijkend e genenkaarten tussenki pe nmen sgebruik tworde n bijhe topspore nva n kandidaatgenen voor bepaalde genetische kenmerken bijd ekip . Ditproefschrift 5. Hoewel hetwaarschijnlij k isda tautosomal edwerggroe i (adw)bi jd eki p inplaat s van een recessief een incompleet recessief kenmerk is,za l dit,omda t gewichtsverschillen tussenheterozygot e(Adwadw) en homozygote(AdwAdw) dieren op een leeftijd van 6 weken nog gering zijn, niet van invloed op het eventuele gebruik vanhe t adwge n inslachtkippelijne n zijn. Ditproefschrift 6. Dezogenaamd e"positiona lcandidat egen eapproach "za l met hetvordere nva n het humane genoomprojec t inbelan gtoenemen . 7. Afsprakenove rhe tgebrui kva nnomenclatuu r isva nessentiee l belangvoo r het op een efficiente manier ontwikkelen vanee n betrouwbare vergelijkende genenkaart. 8. Hoewel het patentrecht oorspronkelijk bedoeld was om wetenschappelijke vooruitgangt e bevorderenwerk t heto p dit moment invee lgevalle naverechts . 9. Met de uitspraak van minister Borst om uitsluitend diagnostische DNA-tests voor behandelbare erfelijke ziekten op de marktto et e laten (VSN contactmagazine augustus 1998),houd t zij geen rekening met het feit dat vroegtijdige kennis omtrent het al dan niet hebben van eenQQbehandelbar e erfelijke ziekte vaak tot andere en beter overwogen keuzes kanleiden . 10. Ind egrondwe tva nee nwar edemocrati ebehoor td emogelijkhei dto t het houden van een referendum opgenoment e zijn. 11. Door het antivaccinatie beleid wat door de Europese Unie bij varkenspest gehanteerdwordt ,krijg the tbegri pvarkensstape l eengehee l andere betekenis. 12. Mensen metee n GSMtelefoo nzij n niet mobielmaa raangelijnd . 13. De uitdrukking "zinloos geweld"impliceer t ten onrechte datgewel doo k zinvol kan zijn. 14. Helaas wordt dewaard e van persoonlijke gezondheid pasjuis t ingeschat als deze niet geheel tot expressie komt. Carolien Ruyter-Spira Wageningen, 13oktobe r 1998 Analysis ofth e Chicken Genome: Mapping of Monogenic Traits. Promotor: dr. ir. E.W. Brascamp hoogleraar ind e veefokkerij Co-promotoren: dr. ir. M.A.M. Groenen universitair docent bij de leerstoelgroep Fokkerij en Genetica dr. M. Georges hoogleraar aan de Universite de Liege, Belgie \;(:C.l V-^ '.. -' UK* Analysis ofth e Chicken Genome: Mapping of Monogenic Traits. Carolien P. Ruyter-Spira Proefschrift ter verkrijging van degraa dva n doctor op gezagva nd e rector magnificus vand e LandbouwuniversiteitWageningen , dr.C.M. Karssen, inhe t openbaar te verdedigen op dinsdag 13oktobe r 1998 des namiddagst evie r uur ind eAula . UVY, CIP-GEGEVENS KONINKLIJKE BIBLIOTHEEK, DEN HAAG Ruyter-Spira, CarolienP . Analysis of thechicke n genome: mapping of monogenic traits / Carolien P. Ruyter- Spira Doctoral thesis, Wageningen Agricultural University. -Wit h ref. -Wit h summary in Dutch. ISBN: 90 - 5485 - 959- 8 Subject headings: genetic linkage map;comparativ e mapping;chicken ; monogenic traits Cover page:"Dominan t White" designed by Dirk Ruyter. Abstract Ruyter-Spira,C.P. , 1998.Analysi s ofth e chicken genome: mapping of monogenic traits. Doctoral thesis, Wageningen Agricultural University, P.O. Box338 ,670 0A H Wageningen,Th e Netherlands. The development of genetic linkage maps infar m animals is progressing rapidly. Linkage maps can be usedt oidentif ygeneti c lociresponsibl e for genetic variation intrait s of economic importance. The ultimate goal is to find the underlying genes involved in these traits. To achieve this, the so called positional candidate gene approach isgainin g inimportance .Thi s approach is based onth e genetic localization of a trait using genetic linkage analysis in livestock species. Subsequent comparative mapping of the trait locus with the gene-rich maps of the human and the mouse may reveal candidate genes for the trait in question. For the construction of comparative maps the genetic localization of many genes needs to be determined. Inthi sthesis, th e development of highly informative microsatellite markers from expressed sequences,whic hwil l contribute toth e (comparative) genetic linkage map ofth e chicken,i sdescribed .I n additiont othis ,th e genomic localization oftw o monogenic traits aredetermine d usinga techniqu e called bulked segregant analysis. Finally, candidate genes for bothtrait s areevaluated . BIBLIOTHEEK LANDBOUWUNIVERSITEn" WAGENINGEN Ter nagedachtenis aan tnijn moeder "Science is a match that man has just gotta light. He thought he was in a room-in moments of devotion, atemple-an dtha t his lightwoul d be reflectedfro m and display walls inscribed with wonderful secrets and pillars carved with philosophical systems wrought intoharmony . Iti sa curiou s sensation,no wtha t the preliminary sputter isove r andth eflam eburn s upclear ,t ose e his hands lit andjus t aglimps e of himself andth e patch he stands on visible, and around him, in place of all that human comfort and beauty he anticipated-darkness still." H.G.Wells, 1891 Voorwoord. In het boekje dat nu voor u ligt staat net onderzoek beschreven dat ik in de periode van September 1994 tot September 1997 bij de leerstoelgroep fokkerij en genetica nebuitgevoerd .Doo rdez eperiod echronologisc ht edoorlope n krijg ikd e kans omd evel e mensendi e mijgesteun d engeholpe n hebbent e bedanken. Allereerst mijn Dirk, die natuurlijk niet alleen in deze periode mijn steun en toeverlaat is,maa ro pwi e ikaltij dka nvertrouwen . Ikvin dhe tmoeilij k dejuist e woorden te vinden om mijn dankbaarheid in uit te drukken en geloof ook niet dat dat ooit mogelijk is.Ji jheb tzovee lvoo r megedaan ,al scolleg ao phe tlab ,al s mijnbest e vriend op het thuisfront en nu ook als grafisch vormgever van dit proefschrift. Fantastisch! Vervolgenswi l ikMartie nGroene nbedanke nvoo rhe tgeve nva nzowe ld emogelijkhei d als de begeleiding om dit onderzoek uit te kunnen voeren. Wat was ik in de wolken toenj e mijee n baan binnen het caserne onderzoek aanbood! Ook gaat mijndan k uit naar alle mensen die het onderzoek praktisch ondersteund hebben en als co-auteur opd e publikaties vermeldstaan . Dan nuwee r terug naar 1994. Het screenen van de cDNA bankword t gestart en leidt al snel tot een publikatie. Helaas gaat het met de GDRDA methode minder voorspoedig, maar door snel een alternatieve strategie te kiezen komt het Eureka moment, waar iedere onderzoeker zijn voldoening en motivatie uit haalt, toch nog, wanneerw eme tsucce she tkenmer k"dominan t wit"wete n te mappen. Ikwi l de leden van mijn begeleidingscommissie; Pirn Zabel, mijn promotor Pirn Brascamp en co- promotorenMiche lGeorge se nMartie nGoene nbedanke nvoo r hun steun en adviezen bijhe tneme nva ndergelijk e besluitene nhe tkritisc hleze nva nall econcep t publicaties. Vervolgens breekt in november 1995 mijn minder mobiele"kruk " periode aan. Inzo' n tijd leer je je collega's pas echt goed kennen. Richard, Maud, Rosilde, Tino, 2xJan , Frits, Tineke, Beja, Pieter, Saskia, Jos, Esther, Paul, Pirn, Antoine, Peter, Annelies, Jos, Martien, hartstikke bedankt voor het dragen van al die kopjes koffie en voor het zorgenvoo r eenfantastisch e sfeero phe t lab.Ja nva nde r Poel, hetwa s echt geweldig datje , samenme t Dirk-Jan enAd , het onderzoek tijdens mijnverlofperiod e voort hebt gezet. Eenmaalteruggekome n konden de krukken gelukkig snel de deurwee r uit, en was het weer een heerlijke "labtijd" waarin de nadruk op het kenmerk autosomale dwerggroei kwam te liggen. Aliene, kleine meid, het was weleens afzien als ik weer eens te laat thuis kwam voor een voeding doordat een experiment was uitgelopen. Bedanktvoo r hetwachten . Nienke, bedankt voor hetmerke ne ndraaie n vand e eitjes. Best leuko pmama' swer khe ?Hen kSchipper , bedankt voorj e technische adviezen bij het isoleren van de embryo's enTori kAyoub i voor de inspirerende samenwerkingo p afstand. Indez etij dwer doo khe tAB Ctea mgevormd .An t en Birgitte,julli e chocola en gevleugeldewoorde nwerkte nzee rstimulerend .Tenslott e zat het praktische werk erop en was het tijd om dit boekje te schrijven. Richard Spelman en Henk Bovenhuis, bedankt voorjulli e bruikbare suggesties bij het schrijven van dediscussie . Entoe n werdji j ernstig ziek Mam.W e deden beiden ons best omjanuar i te halen; ik zouda npromovere ne nji jzo umi jvanui td ezaa laanmoedigen . We hebben het beiden nietgered . Ikmi sj eelk edag ! Jijblijf t mijngrot evoorbeeld ,e n hebt mijto t het eind aan toe gestimuleerdo mdi t boekje toch aft e maken Enhie r ligt hetdan . Carolien Contents Chapter 1 General introduction 9 1.1 Genome analysis infar m animals 11 1.2Analysi s of the chicken genome 12 1.3Mappin g of monogenic traits infar m animals 14 1.4Comparativ e mapping inth e chicken 15 1.5 Scope of this thesis 21 Chapter 2 Development and mapping of polymorphic microsatellite markers derived from achicke n brain cDNA library. 29 Chapter 3 Developing microsatellite markers from cDNA: atoo l for adding expressed sequences to the genetic linkage map ofth echicken . 43 Chapter 4 Bulked segregant analysis using microsatellites: mapping of the dominant white locus inth echicken . 55 Chapter 5 The HMGI-Cgen e is a likely candidate for the autosomal dwarf locus inth echicken .
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