Figure 1.
The LGR6 frameshift variant is linked with low levels of LGR6 expression. (A) Alignment of the protein sequence between LGR6 with or without the rs74355478 variant. Dark purple sequences indicate the aligned amino acids, whereas the asterisk (∗) represents the site where an alanine (A) is replaced by an arginine (R) leading to a frameshift mutation and generating a premature stop codon. The secondary structures of LGR6 are indicated in the protein sequence, and the colors represent the different transmembrane helices. (B) Secondary (left) and 3-dimensional (right) structure of LGR6. Colors indicate the different transmembrane helices of LGR6, whereas the arrows point to the location of the single nucleotide polymorphism (SNP). LGR6 expression in granulocytes (C, top) and monocytes (D, top) from participants with the rs74355478 variant in LGR6 (variant group) and controls (control group) was evaluated using flow cytometry and fluorescently conjugated antibodies to this receptor. To assess the LGR6 expression of neutrophils (C, bottom) and different monocyte subsets (D, bottom), whole blood from participants was incubated with antibodies against lineage markers to identify neutrophils (CD16+), classical (CD14++CD16+), intermediate (CD14++CD16++), and nonclassical (CD14+CD16++) monocytes, and the expression of the receptor was evaluated using antibodies against LGR6. (E) Monocytes were isolated from whole blood of participants from the variant and control groups and differentiated into monocyte-derived macrophages using granulocyte-macrophage colony-stimulating factor. On day 7, cells were lifted, and the expression of LGR6 was evaluated using fluorescently conjugated antibodies to this receptor. Statistical differences between variant and control groups were determined using the 1-tailed Mann-Whitney test, and P values are displayed. For panels C-D (top), results are representative of 7 for variants and 9 for controls. For panels C-D (bottom) and E, results are representative of 4 for variants and 4 for controls.

The LGR6 frameshift variant is linked with low levels of LGR6 expression. (A) Alignment of the protein sequence between LGR6 with or without the rs74355478 variant. Dark purple sequences indicate the aligned amino acids, whereas the asterisk (∗) represents the site where an alanine (A) is replaced by an arginine (R) leading to a frameshift mutation and generating a premature stop codon. The secondary structures of LGR6 are indicated in the protein sequence, and the colors represent the different transmembrane helices. (B) Secondary (left) and 3-dimensional (right) structure of LGR6. Colors indicate the different transmembrane helices of LGR6, whereas the arrows point to the location of the single nucleotide polymorphism (SNP). LGR6 expression in granulocytes (C, top) and monocytes (D, top) from participants with the rs74355478 variant in LGR6 (variant group) and controls (control group) was evaluated using flow cytometry and fluorescently conjugated antibodies to this receptor. To assess the LGR6 expression of neutrophils (C, bottom) and different monocyte subsets (D, bottom), whole blood from participants was incubated with antibodies against lineage markers to identify neutrophils (CD16+), classical (CD14++CD16+), intermediate (CD14++CD16++), and nonclassical (CD14+CD16++) monocytes, and the expression of the receptor was evaluated using antibodies against LGR6. (E) Monocytes were isolated from whole blood of participants from the variant and control groups and differentiated into monocyte-derived macrophages using granulocyte-macrophage colony-stimulating factor. On day 7, cells were lifted, and the expression of LGR6 was evaluated using fluorescently conjugated antibodies to this receptor. Statistical differences between variant and control groups were determined using the 1-tailed Mann-Whitney test, and P values are displayed. For panels C-D (top), results are representative of 7 for variants and 9 for controls. For panels C-D (bottom) and E, results are representative of 4 for variants and 4 for controls.

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