Blom van Assendelft, Margaretha van

English

The structure and regulation of the human β -like globin gene cluster has been studied extensively. Genetic disorders connected with this gene cluster are responsible for human diseases associated with high levels of morbidity and mortality, such as β-thalassaemia and sickle cell anaemia. The work described in this thesis is concerned with a novel tissue-specific regulatory element. ... Zie: Summar

Dissertations of the University of Groningen

   University of GroningenDominant control region of the human β- like globin gene clusterBlom van Assendelft, Margaretha vanIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1989Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Blom van Assendelft, M. V. (1989). Dominant control region of the human β- like globin gene cluster. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 04-06-2022SUMMARYThe  s t ruc tu re  and  regu la t i on  o f  t he  human  p -1 i ke  g lob in  gene  c lus te r  has  beens tud ied  ex tens i ve l y .  Gene t i c  d j so rde rs  connec ted  w i th  t h i s  gene  c lus te r  a rerespons ib le  f o r  human  d j seases  assoc ia ted  w i th  h igh  l eve1s  o f  morb id i t y  andmor ta l i t y ,  such  as  p - tha ïassaemia  and  s i ck le  ce l l  anaemia .  The  work  desc r i bedin  t h i s  t hes i s  j s  conce rned  w i th  a  nove ' l  t i s sue -spec i f i c  r egu la to ry  e lemen t .The  human  p -g lob in  Domjnan t  con t ro l  Reg ion  (DcR)  con fe rs  i n teg ra t i on -s i t ei ndependen t ,  copy -number  re la ted ,  h igh -1eve l  exp ress ion  to  a  l i nked  p -g lob ingene  i n  a  t i s sue -spec i f i c  manner  i n  t r ansgen i c  m ice  ( see  chap te r  2 )  and  mousee ry th ro leukemja  (MEL)  ce11s  ( chap te r  3 ) .  The  d i scove ry  o f  t he  human  p -g lob inDCR sequences j  s  an important  s tep towards somat i  c  gene therapy fortha lassaemja  nd  s i ck le -ce11  pa t i en t s  (Chap te r  5 ) .T h e  g l o b i n  D C R  a s  o r i g i n a l l y  c l o n e d  i n  t h e  " m i n j - l o c u s "  c o s m i d  c o n s t r u c tspans 33kb of  DNA sequences.  Delet ion constructs were made to determined j f f e ren t  f unc t j ona l  a reas  w j th jn  t he  DCR sequences  ( chap te r  3  and  4 ) .  I t  i snow though t  t ha t  t he  DCR func t i ona l  e l emen ts  a re  l oca ted  w i th in  de f i nedreg ions  (as  d i scussed  i n  chap te r  5 )  cha rac te r i zed  by  t he  p resence  o f  s t rongDNase  I hype rsens i t i ve  s j t es  (Chap te rs  2  and  3 ) .The  human  p -g lob in  DCR can  con fe r  h igh  l eve l  exp ress ion  to  o the r  e ry th ro idgenes '  name ly  t he  human  a -  and  1 -g lob in  genes  ( chap te r  5 ) ,  and  non -e ry th ro idgenes  such  as  Thy -1  and  t k -neo  (Chap te r  3 ) .The  recen t  d i scove ry  o f  a  reg ion  3 ' f l ank ing  to  t he  human  T -ce l1  spec i f i c  cD2gene  w i th  f unc t i ona l  p rope r t i es  s im i l a r  t o  t hose  o f  t he  human  p -g lob in  DCR(d i scussed  i n  Chap te r  5 )  sugges ts  t ha t  exp ress ion  o f  o the r  t i s sue -spec j f i cgenes  m igh t  a l so  be  regu la ted  by  DCR- l i ke  e lemen ts .9 1

Dominant control region of the human β- like globin gene cluster

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Dominant control region of the human β- like globin gene cluster

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