2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Recognizing the Promise and Potential Pitfalls of Genomic Medicine Through Routine Rapid Whole Genome Sequencing

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Genome sequencing (GS) has several advantages over capture-based next-generation sequencing (NGS) methods, especially for critically ill patients who need rapid testing. Studies have shown the clinical utility of rapid testing, but this potential needs to be realized through routine testing. GS requires minimal processing, reducing the time from sample receipt to sequencing. It produces non-biased even sequence coverage across the genome, allowing detection of deep-intronic variants. The evenness of coverage also enables high specificity for copy number variant (CNV) calling. In addition to deletions and duplications, GS can confidently call absence of heterozygosity, aneuploidy, mosaic deletions and duplications, and uniparental disomy.<br /><br />Whole genome sequencing (WGS) from dried blood spots (DBS) reduces the challenges associated with sample collection from ill newborns, with minimal processing resulting in rapid turnaround time. WGS also provides deep coverage of mitochondrial DNA sequences. Research has shown a diagnostic yield of 45% across a mixed cohort of pediatric and adult cases. WGS can identify different types of variants, including single nucleotide variants (SNVs), CNVs, and variants in mitochondrial DNA. Proband vs. trio analyses from 285 pediatric cases showed similar diagnostic yields. In terms of diagnostic findings, pathogenic and likely pathogenic findings were identified in 14.1% and 2.9% of cases, respectively.<br /><br />WGS from DBS has several advantages, including better coverage of intronic sequences, improved CNV calling, and deep mitochondrial sequencing. It also has potential for cCMV detection, metagenomics analysis, and testing for amino acids/organic acids/acylcarnitine. Using DBS for testing allows for comprehensive biochemical testing and increased diagnostic yield due to the detection of deep intronic and cytogenomic variants. WGS also provides high coverage of mitochondrial DNA, enabling the detection of pathogenic variants that may be missed by other sequencing methods.

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Presenting Author - Lora H. Bean, PhD; Co-Author - Christin D. Collins, PhD, FACMG; Co-Author - Fen Guo, PhD, FACMG, FCCMG; Co-Author - Jorune Balciuniene, PhD, FACMG, ErCLG; Co-Author - Xiangwen Chen-Deutsch, PhD; Co-Author - Babi Ramesh Reddy Nallamilli, PhD; Co-Author - Naga M. Guruju, PhD, FACMG; Co-Author - Rizwan Yousaf, PhD; Co-Author - Kristina Fura, BS; Co-Author - Amber Woodman, BS; Co-Author - Ruby Liu, PhD, CGC; Co-Author - Jenny Zhang, MS; Co-Author - Kate Liebmann, MS; Co-Author - Julia C. Gerow, BS; Co-Author - Ephrem Chin, MBA, BTech(Hon), MB(ASCP) CM, QLC CM, CGMBS; Co-Author - Madhuri Hegde, PhD, FACMG;

Meta Tag

Genetic Testing

Genome sequencing

Molecular Cytogenetics

NextGen Sequencing

Sequencing

Co-Author Christin D. Collins, PhD, FACMG

Co-Author Fen Guo, PhD, FACMG, FCCMG

Co-Author Jorune Balciuniene, PhD, FACMG, ErCLG

Co-Author Xiangwen Chen-Deutsch, PhD

Co-Author Babi Ramesh Reddy Nallamilli, PhD

Co-Author Naga M. Guruju, PhD, FACMG

Co-Author Rizwan Yousaf, PhD

Co-Author Kristina Fura, BS

Co-Author Amber Woodman, BS

Co-Author Ruby Liu, PhD, CGC

Co-Author Jenny Zhang, MS

Co-Author Kate Liebmann, MS

Co-Author Julia C. Gerow, BS

Co-Author Ephrem Chin, MBA, BTech(Hon), MB(ASCP) CM, QLC CM, CGMBS

Co-Author Madhuri Hegde, PhD, FACMG

Presenting Author Lora H. Bean, PhD

Keywords

genome sequencing

capture-based NGS

rapid testing

even sequence coverage

copy number variant calling

WGS from dried blood spots

mitochondrial DNA sequencing

diagnostic yield

intronic sequences

cCMV detection