Linked Life Data

19808799

Source:http://linkedlifedata.com/resource/pubmed/id/19808799

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
R2
pubmed:dateCreated
2009-10-7
pubmed:abstractText
Increased levels of fetal hemoglobin (HbF, alpha(2)gamma(2)) are of no consequence in healthy adults, but confer major clinical benefits in patients with sickle cell anemia (SCA) and beta thalassemia, diseases that represent major public health problems. Inter-individual HbF variation is largely genetically controlled, with one extreme caused by mutations involving the beta globin gene (HBB) complex, historically referred to as pancellular hereditary persistence of fetal hemoglobin (HPFH). These Mendelian forms of HPFH are rare and do not explain the common form of heterocellular HPFH which represents the upper tail of normal HbF variation, and is clearly inherited as a quantitative genetic trait. Genetic studies have identified three major quantitative trait loci (QTLs) (Xmn1-HBG2, HBS1L-MYB intergenic region on chromosome 6q23, and BCL11A on chromosome 2p16) that account for 20-50% of the common variation in HbF levels in patients with SCA and beta thalassemia, and in healthy adults. Two of the major QTLs include oncogenes, emphasizing the importance of cell proliferation and differentiation as an important contribution to the HbF phenotype. The review traces the story of HbF quantitative genetics that uncannily mirrors the changing focus in genetic methodology, from candidate genes through positional cloning, to genome-wide association, that have expedited the dissection of the genetic architecture underlying HbF variability. These genetic results have already provided remarkable insights into molecular mechanisms that underlie the hemoglobin 'switch'.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R216-23
pubmed:dateRevised
2010-10-18
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Control of fetal hemoglobin: new insights emerging from genomics and clinical implications.
pubmed:affiliation
Division of Gene and Cell Based Therapy, King's College London School of Medicine, Molecular Haematology, Denmark Hill Campus, London SE5 9NU, UK. sl.thein@kcl.ac.uk
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural