Genetic Modifiers of Sickle Cell Disease

Abstract

Sickle cell disease is one of the best characterized human monogenic disorders. Complex genotype/phenotype correlations clearly demonstrate the interaction of multiple genetic and environmental factors. In the last 20 years, scientific research has applied genetic approaches to dissect some of these modifiers. This review highlights the more recent genetic association studies that have been applied to unravel the genetic modifiers of sickle cell disease including Hb F genetics, and the key genetic variants identified. Illumination of such modifying factors may guide future therapeutic interventions and improve prediction of disease severity, with implications for genetic counseling, prenatal diagnosis and implementation of high risk therapy.

Long-Term Engraftment and Fetal Globin Induction upon BCL11A Gene Editing in Bone-Marrow-Derived CD34 + Hematopoietic Stem and Progenitor Cells

“…Fetal hemoglobin (HbF, α2γ2) is recognized as one of the most important disease modifiers for SCD because it not only inhibits HbS polymerization, but also reduces mean corpuscular HbS concentration 5, 37, 38, 39, 40. HbF is the predominant hemoglobin at birth, but it typically falls below 1% of total hemoglobin within a year and is replaced by adult hemoglobin (α2β2) as the switch from γ- to β-globin in the β-globin locus occurs 4 .…”

The Hidden Complexity of Mendelian Traits across Natural Yeast Populations

“…Similarly, monogenic traits can be influenced by multiple genes in specific genetic backgrounds (Badano and Katsanis, 2002; Cooper et al, 2013; Dorfman, 2012; Nadeau, 2001; Thein, 2011). In fact, it is increasingly evident that monogenic mutations do not always strictly adhere to Mendelian inheritance (Cooper et al, 2013; Dorfman, 2012; Nadeau, 2001).…”

Clinical Factors Associated With Morbidity and Mortality in Patients Admitted with Sickle Cell Disease

“…Dactylitis and splenic sequestration are common in children under five years of age, while strokes and leg ulcerations are common during adolescence and chronic organ damage is most common in adulthood (5,6). Within genotypes, the manifestation of the disease is highly variable (7,8).…”