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Sequence view of the genomic region surrounding the RHD transcription start site (chr1:25272354–25272950, hg38), highlighting two AG-prioritized non-coding variants selected for experimental validation: chr1:25272422 (c.1–83 C>T, highlighted in yellow) and chr1:25272434 (G>A, highlighted in orange). The displayed nucleotide sequence provides the exact genomic context used for sgRNA design and evaluation of the BE4max editing window, including the relative positions of target bases and potential bystander nucleotides. Both variants reside within a promoter-proximal regulatory region predicted by AG to exert suppressive effects on RHD expression.

Journal: bioRxiv

Article Title: AlphaGenome-enabled analysis of non-coding regulatory variants underlying RHD expression

doi: 10.64898/2026.01.21.700828

Figure Lengend Snippet: Sequence view of the genomic region surrounding the RHD transcription start site (chr1:25272354–25272950, hg38), highlighting two AG-prioritized non-coding variants selected for experimental validation: chr1:25272422 (c.1–83 C>T, highlighted in yellow) and chr1:25272434 (G>A, highlighted in orange). The displayed nucleotide sequence provides the exact genomic context used for sgRNA design and evaluation of the BE4max editing window, including the relative positions of target bases and potential bystander nucleotides. Both variants reside within a promoter-proximal regulatory region predicted by AG to exert suppressive effects on RHD expression.

Article Snippet: To introduce the target SNPs (chr1:25272422 C>T and chr1:25272434 G>A), we employed BE4max (Addgene: #112094), a fourth-generation cytosine base editor consisting of a rat APOBEC1 cytidine deaminase fused to Streptococcus pyogenes Cas9 nickase (nCas9, D10A mutation) and two copies of uracil glycosylase inhibitor (UGI).

Techniques: Sequencing, Biomarker Discovery, Expressing