Anemia, Sickle Cell study with SNP/CNV (Array) data on dbGaP (879 participants)

phs003748 — Genomic and Phenotypic Profile of Sickle Cell Disease in Human Population    in Cameroon

<p>Sickle cell disease (SCD) is caused by a biallelic single nucleotide substitution in the beta-globin gene (<a href="https://www.ncbi.nlm.nih.gov/gene/3043">HBB</a>), resulting in an amino acid substitution, Glu7Val, formerly known as Glu6Val. An estimated 300,000 babies with SCD are born worldwide each year, with nearly 75% of these births being in sub-Saharan Africa. In Africa, at least 30-50% of children with untreated SCD die before the age of 5 years. Therefore, accelerating the path for novel therapies for SCD through genomics research on fetal hemoglobin (HbF) is critical. Variants in the currently known HbF‐modulating genes/loci, i.e., <a href="https://www.ncbi.nlm.nih.gov/gene/53335">BCL11A</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/10767">HBS1L</a>-<a href="https://www.ncbi.nlm.nih.gov/gene/4602">MYB</a>, and XmnI-<a href="https://www.ncbi.nlm.nih.gov/gene/3048">HBG2</a>, explain only 10-20% of the variation of HbF levels in African individuals with SCD, compared with nearly 50% of the variation in HbF levels among Europeans. Expanding genomic research in populations of African ancestry could uncover the missing heritability of HbF-promoting loci. This study used the Human Heredity and Health (H3Africa) consortium SNP genotyping array developed from whole genome enriched for common variants in sub-Saharan Africans to investigate genomic variations associated with HbF levels in individuals with sickle cell anemia of the HbSS genotype from Cameroon. Two of the previously described loci, <a href="https://www.ncbi.nlm.nih.gov/gene/53335">BCL11A</a> and <a href="https://www.ncbi.nlm.nih.gov/gene/10767">HBS1L</a>-<a href="https://www.ncbi.nlm.nih.gov/gene/4602">MYB</a> were replicated, while a novel locus on chromosome 13 mapping to <a href="https://www.ncbi.nlm.nih.gov/gene/2321">FLT1</a> was uncovered. The study therefore opens up a novel avenue for exploring SCD gene therapy.</p>