File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression
  • Basic View
  • Metadata View
  • XML View
TitleA 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression
 
AuthorsFarrell, JJ7
Sherva, RM7
Chen, ZY7
Luo, HY7
Chu, BF7
Ha, SY1
Li, CK6
Lee, ACW3
Li, RCH3
Li, CK2
Yuen, HL4
So, JCC1
Ma, ESK1
Chan, LC1
Chan, V1
Sebastiani, P5
Farrer, LA7
Baldwin, CT7
Steinberg, MH7
Chui, DHK7
 
Issue Date2011
 
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
 
CitationBlood, 2011, v. 117 n. 18, p. 4935-4945 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2010-11-317081
 
AbstractFetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations. © 2011 by The American Society of Hematology.
 
ISSN0006-4971
2012 Impact Factor: 9.06
2012 SCImago Journal Rankings: 4.553
 
DOIhttp://dx.doi.org/10.1182/blood-2010-11-317081
 
PubMed Central IDPMC3100700
 
ISI Accession Number IDWOS:000290275700038
Funding AgencyGrant Number
National Institute of Diabetes and Digestive and Kidney DiseasesRO1 DK069646
National Heart, Lung, and Blood InstituteRO1 HL068970
Funding Information:

This investigation was supported by National Institute of Diabetes and Digestive and Kidney Diseases (grant RO1 DK069646; D.H.K.C.) and National Heart, Lung, and Blood Institute (grant RO1 HL068970; M.H.S.).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorFarrell, JJ
 
dc.contributor.authorSherva, RM
 
dc.contributor.authorChen, ZY
 
dc.contributor.authorLuo, HY
 
dc.contributor.authorChu, BF
 
dc.contributor.authorHa, SY
 
dc.contributor.authorLi, CK
 
dc.contributor.authorLee, ACW
 
dc.contributor.authorLi, RCH
 
dc.contributor.authorLi, CK
 
dc.contributor.authorYuen, HL
 
dc.contributor.authorSo, JCC
 
dc.contributor.authorMa, ESK
 
dc.contributor.authorChan, LC
 
dc.contributor.authorChan, V
 
dc.contributor.authorSebastiani, P
 
dc.contributor.authorFarrer, LA
 
dc.contributor.authorBaldwin, CT
 
dc.contributor.authorSteinberg, MH
 
dc.contributor.authorChui, DHK
 
dc.date.accessioned2011-09-23T06:02:15Z
 
dc.date.available2011-09-23T06:02:15Z
 
dc.date.issued2011
 
dc.description.abstractFetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations. © 2011 by The American Society of Hematology.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationBlood, 2011, v. 117 n. 18, p. 4935-4945 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2010-11-317081
 
dc.identifier.citeulike8976138
 
dc.identifier.doihttp://dx.doi.org/10.1182/blood-2010-11-317081
 
dc.identifier.epage4945
 
dc.identifier.hkuros192825
 
dc.identifier.isiWOS:000290275700038
Funding AgencyGrant Number
National Institute of Diabetes and Digestive and Kidney DiseasesRO1 DK069646
National Heart, Lung, and Blood InstituteRO1 HL068970
Funding Information:

This investigation was supported by National Institute of Diabetes and Digestive and Kidney Diseases (grant RO1 DK069646; D.H.K.C.) and National Heart, Lung, and Blood Institute (grant RO1 HL068970; M.H.S.).

 
dc.identifier.issn0006-4971
2012 Impact Factor: 9.06
2012 SCImago Journal Rankings: 4.553
 
dc.identifier.issue18
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC3100700
 
dc.identifier.pmid21385855
 
dc.identifier.scopuseid_2-s2.0-79955977896
 
dc.identifier.spage4935
 
dc.identifier.urihttp://hdl.handle.net/10722/139942
 
dc.identifier.volume117
 
dc.languageeng
 
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofBlood
 
dc.relation.referencesReferences in Scopus
 
dc.rightsThis research was originally published in The Hematologist: ASH News and Reports. Author(s). Title. The Hematologist: ASH News and Reports. Year;Vol,Issue:pp-pp. © the American Society of Hematology.
 
dc.subject.meshAsian Continental Ancestry Group - genetics
 
dc.subject.meshChromosomes, Human, Pair 6 - genetics
 
dc.subject.meshFetal Hemoglobin - genetics
 
dc.subject.meshGenes, myb
 
dc.subject.meshSequence Deletion
 
dc.titleA 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Farrell, JJ</contributor.author>
<contributor.author>Sherva, RM</contributor.author>
<contributor.author>Chen, ZY</contributor.author>
<contributor.author>Luo, HY</contributor.author>
<contributor.author>Chu, BF</contributor.author>
<contributor.author>Ha, SY</contributor.author>
<contributor.author>Li, CK</contributor.author>
<contributor.author>Lee, ACW</contributor.author>
<contributor.author>Li, RCH</contributor.author>
<contributor.author>Li, CK</contributor.author>
<contributor.author>Yuen, HL</contributor.author>
<contributor.author>So, JCC</contributor.author>
<contributor.author>Ma, ESK</contributor.author>
<contributor.author>Chan, LC</contributor.author>
<contributor.author>Chan, V</contributor.author>
<contributor.author>Sebastiani, P</contributor.author>
<contributor.author>Farrer, LA</contributor.author>
<contributor.author>Baldwin, CT</contributor.author>
<contributor.author>Steinberg, MH</contributor.author>
<contributor.author>Chui, DHK</contributor.author>
<date.accessioned>2011-09-23T06:02:15Z</date.accessioned>
<date.available>2011-09-23T06:02:15Z</date.available>
<date.issued>2011</date.issued>
<identifier.citation>Blood, 2011, v. 117 n. 18, p. 4935-4945</identifier.citation>
<identifier.issn>0006-4971</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/139942</identifier.uri>
<description.abstract>Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese &#946;-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations. &#169; 2011 by The American Society of Hematology.</description.abstract>
<language>eng</language>
<publisher>American Society of Hematology. The Journal&apos;s web site is located at http://bloodjournal.hematologylibrary.org/</publisher>
<relation.ispartof>Blood</relation.ispartof>
<rights>This research was originally published in The Hematologist: ASH News and Reports. Author(s). Title. The Hematologist: ASH News and Reports. Year;Vol,Issue:pp-pp. &#169; the American Society of Hematology.</rights>
<subject.mesh>Asian Continental Ancestry Group - genetics</subject.mesh>
<subject.mesh>Chromosomes, Human, Pair 6 - genetics</subject.mesh>
<subject.mesh>Fetal Hemoglobin - genetics</subject.mesh>
<subject.mesh>Genes, myb</subject.mesh>
<subject.mesh>Sequence Deletion</subject.mesh>
<title>A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression</title>
<type>Article</type>
<identifier.openurl>http://library.hku.hk:4550/resserv?sid=HKU:IR&amp;issn=0006-4971&amp;volume=117&amp;issue=18&amp;spage=4935&amp;epage=4945&amp;date=2011&amp;atitle=A+3-bp+deletion+in+the+HBS1L-MYB+intergenic+region+on+chromosome+6q23+is+associated+with+HbF+expression</identifier.openurl>
<description.nature>Link_to_subscribed_fulltext</description.nature>
<identifier.doi>10.1182/blood-2010-11-317081</identifier.doi>
<identifier.pmid>21385855</identifier.pmid>
<identifier.pmcid>PMC3100700</identifier.pmcid>
<identifier.scopus>eid_2-s2.0-79955977896</identifier.scopus>
<identifier.hkuros>192825</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-79955977896&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>117</identifier.volume>
<identifier.issue>18</identifier.issue>
<identifier.spage>4935</identifier.spage>
<identifier.epage>4945</identifier.epage>
<identifier.isi>WOS:000290275700038</identifier.isi>
<publisher.place>United States</publisher.place>
<identifier.citeulike>8976138</identifier.citeulike>
</item>
Author Affiliations
  1. The University of Hong Kong
  2. Princess Margaret Hospital Hong Kong
  3. Tuen Mun Hospital
  4. Queen Elizabeth Hospital Hong Kong
  5. Boston University School of Public Health
  6. Prince of Wales Hospital Hong Kong
  7. Boston University School of Medicine