title: ASH1L (a histone methyltransferase protein) is a novel candidate globin gene regulator revealed by genetic study of an English family with beta-thalassaemia unlinked to the beta-globin locus.
abstract: In 1993, we described an English family with beta-thalassaemia that was not linked to the beta-globin locus. Whole genome sequence analyses revealed potential causative mutations in 15 different genes, of which 4 were consistently and uniquely associated with the phenotype in all 7 affected family members, also confirmed by genetic linkage analysis. Of the 4 genes, which are present in a centromeric region of chromosome 1, ASH1L was proposed as causative through functional mRNA knock-down and chromatin-immunoprecipitation studies in human erythroid progenitor cells. Our data suggest a putative role for ASH1L (Trithorax protein) in the regulation of globin genes.
authors.affiliation: Molecular Haematology, Division of Cancer Studies, King's College London Faculty of Life Sciences and Medicine, London, SE5 9NU, UK.
authors.forename: Amandine
authors.initials: A
authors.lastname: Breton
authors.affiliation: Molecular Haematology, Division of Cancer Studies, King's College London Faculty of Life Sciences and Medicine, London, SE5 9NU, UK.
authors.forename: Andria
authors.initials: A
authors.lastname: Theodorou
authors.affiliation: Molecular Haematology, Division of Cancer Studies, King's College London Faculty of Life Sciences and Medicine, London, SE5 9NU, UK.
authors.forename: Suleyman
authors.initials: S
authors.lastname: Aktuna
authors.affiliation: Molecular Haematology, Division of Cancer Studies, King's College London Faculty of Life Sciences and Medicine, London, SE5 9NU, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Sonzogni
authors.affiliation: Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, SE5 9RS, UK.
authors.forename: David
authors.initials: D
authors.lastname: Darling
authors.affiliation: Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, SE5 9RS, UK.
authors.forename: Lucas
authors.initials: L
authors.lastname: Chan
authors.affiliation: Molecular Haematology, Division of Cancer Studies, King's College London Faculty of Life Sciences and Medicine, London, SE5 9NU, UK.
authors.forename: Stephan
authors.initials: S
authors.lastname: Menzel
authors.affiliation: Department of Bioinformatics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van der Spek
authors.affiliation: Department of Bioinformatics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Sigrid M A
authors.initials: SM
authors.lastname: Swagemakers
authors.affiliation: Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.|Netherlands Consortium for Systems Biology, Erasmus MC, Rotterdam, The Netherlands.|Centre for Biomedical Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.affiliation: Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.|Netherlands Consortium for Systems Biology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Sjaak
authors.identifier: http://orcid.org/0000-0002-3690-1201
authors.initials: S
authors.lastname: Philipsen
authors.affiliation: Molecular Haematology, Division of Cancer Studies, King's College London Faculty of Life Sciences and Medicine, London, SE5 9NU, UK. sl.thein@nih.gov.|Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, SE5 9RS, UK. sl.thein@nih.gov.
authors.forename: Swee Lay
authors.initials: SL
authors.lastname: Thein
mesh_terms: D002460:Cell Line; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D008040:Genetic Linkage; D014644:Genetic Variation; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D006801:Humans; D010641:Phenotype; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism*; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D014157:Transcription Factors; D055544:beta-Globins; C490911:ASH1L protein, human; D011495:Histone-Lysine N-Methyltransferase
keywords: 
  ASH1L
  ; Trithorax protein; beta-thalassaemia