Genetic modifiers of sickle cell disease.
Sickle cell anemia is associated with unusual clinical heterogeneity for a Mendelian disorder. Fetal hemoglobin concentration and coincident α thalassemia, both which directly affect the sickle erythrocyte, are the major modulators of the phenotype of disease. Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia would be prognostically useful, could inform personalized therapeutics, and might help the discovery of new "druggable" pathophysiologic targets. Genotype-phenotype association studies have been used to identify novel genetic modifiers. In the future, whole genome sequencing with its promise of discovering hitherto unsuspected variants could add to our understanding of the genetic modifiers of this disease.
Division of Hematology/Oncology, Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA. mhsteinb@bu.edu
Martin H
MH
Steinberg
Paola
P
Sebastiani
D000755:Anemia, Sickle Cell / Q000235:genetics*; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D008297:Male; D017085:alpha-Thalassemia / Q000235:genetics
D005319:Fetal Hemoglobin