The authors developed a novel method for targeted sequencing of genomic regions using ultra-long oligonucleotides as "baits" to enrich specific templates from a pool of genomic DNA. The method involves transcribing the oligonucleotides into RNA, which is then used to hybridize and capture the target sequences. This approach was tested on 170-mer baits targeting coding exons and four genomic regions using Illumina sequencing. The results showed that about 90% of uniquely aligning bases fell on or near the bait sequence, with up to 50% lying on exons. The method demonstrated high uniformity in coverage, with ~60% of target bases in the exonic "catch" and ~80% in the regional catch having at least half the mean coverage. One lane of Illumina sequencing was sufficient to call high-confidence genotypes for 89% of the targeted exon space. The authors also assessed the specificity, reproducibility, and accuracy of SNP detection, finding excellent concordance with known genotypes and low discordance rates. The method is flexible, scalable, and efficient, making it suitable for deep targeted sequencing of exons and large genomic regions.The authors developed a novel method for targeted sequencing of genomic regions using ultra-long oligonucleotides as "baits" to enrich specific templates from a pool of genomic DNA. The method involves transcribing the oligonucleotides into RNA, which is then used to hybridize and capture the target sequences. This approach was tested on 170-mer baits targeting coding exons and four genomic regions using Illumina sequencing. The results showed that about 90% of uniquely aligning bases fell on or near the bait sequence, with up to 50% lying on exons. The method demonstrated high uniformity in coverage, with ~60% of target bases in the exonic "catch" and ~80% in the regional catch having at least half the mean coverage. One lane of Illumina sequencing was sufficient to call high-confidence genotypes for 89% of the targeted exon space. The authors also assessed the specificity, reproducibility, and accuracy of SNP detection, finding excellent concordance with known genotypes and low discordance rates. The method is flexible, scalable, and efficient, making it suitable for deep targeted sequencing of exons and large genomic regions.