CRISPR and single-cell sequencing pinpoint causal genetic variants for traits and diseases sciencemagazine
, a target based on its promise for reversing sickle cell anemia, but they did not know which exact variant drives its production.
CRISPR has now been used in clinical trials to edit this region in bone marrow cells of dozens of patients with sickle cell anemia. After the modified cells are infused back into patients, they begin producing fetal hemoglobin, which displaces the mutated adult form of hemoglobin, effectively curing them of sickle-cell disease.
In their study, the researchers illustrated the use of STING-seq to discover target genes of noncoding variants for blood traits. Blood traits—such as the percentages of platelets, white blood cells, and red blood cells—are easy to measure in routine blood tests and have been well-studied in GWAS. As a result, the researchers were able to use GWAS representing nearly 750,000 people from diverse backgrounds to study blood traits.
After CRISPR silencing of regions identified by GWAS, the researchers looked at the expression of nearby genes in individual cells to see if particular genes were turned on or off. If they saw a difference in gene expression between cells where variants were and were not silenced, they could link specific noncoding regions to target genes.
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