2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Exon-level copy number variations identified by whole genome sequencing in previously undiagnosed patients with rare hereditary diseases

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A study conducted by the Greenwood Genetic Center examined the use of whole genome sequencing (WGS) to identify copy number variations (CNVs) in patients with rare hereditary diseases. The WGS analysis was performed using the Illumina TruSeq Nano DNA Library Prep Kit and the Illumina NovaSeqTM 6000 System. The DNA sequence was aligned and compared to the human genome build 19, and the average depth of coverage was calculated.<br /><br />The study compared the results of WGS with previous microarray-based testing. Several cases were identified where WGS identified CNVs that were missed by microarray analysis. Three representative cases were described, including CNVs ranging from 3.6 kb to 11.8 kb in size. These CNVs affected genes associated with rare Mendelian diseases.<br /><br />Microarray analysis using the Affymetrix CytoScan HD/XON Microarray Platform was also performed to analyze genomic DNA. The Chromosome Analysis Suite (ChAS) software was used for the analysis, and all copy number changes were determined using the human genome build 19.<br /><br />Sanger sequencing was used for breakpoint mapping/refinement. Genomic DNA was amplified by PCR, and the amplified product was sequenced using the Sanger dideoxy method.<br /><br />The study found that WGS can identify small CNVs that may not be detected by microarray-based platforms. The breakpoints identified by WGS were confirmed by Sanger sequencing. The use of WGS can improve the molecular diagnostic yield and impact patient care positively.<br /><br />The study concluded that WGS is a valuable tool in clinical genetic testing and can complement microarray-based analysis. It can identify CNVs missed by microarrays and provide additional information for diagnosis and patient care.<br /><br />The study references previous research on the applications and benefits of WGS in clinical practice. It acknowledges the patients and teams involved in the study and cites relevant literature on genomic sequencing in clinical practice.<br /><br />Overall, this study highlights the advantages of WGS in identifying CNVs associated with rare hereditary diseases and emphasizes its potential impact on improving patient care.

Asset Subtitle

Presenting Author - Jiyong Wang, PhD; Co-Author - Raymond C. Caylor, PhD, FACMG; Co-Author - Julie R. Jones, PhD, FACMG; Co-Author - Jennifer A. Lee, PhD, FACMG; Co-Author - Raymond J. Louie, PhD, FACMG; Co-Author - Benjamin A. Hilton, PhD; Co-Author - Barbara R. DuPont, PhD, FACMG; Co-Author - Kameryn M. Butler, PhD, FACMG;

Meta Tag

Clinical Cytogenetics

Cytogenetics

Genetic Testing

Genome sequencing

Microarray

Molecular Cytogenetics

NextGen Sequencing

Pathology

Sequencing

Co-Author Raymond C. Caylor, PhD, FACMG

Co-Author Julie R. Jones, PhD, FACMG

Co-Author Jennifer A. Lee, PhD, FACMG

Co-Author Raymond J. Louie, PhD, FACMG

Co-Author Benjamin A. Hilton, PhD

Co-Author Barbara R. DuPont, PhD, FACMG

Co-Author Kameryn M. Butler, PhD, FACMG

Presenting Author Jiyong Wang, PhD

Keywords

Greenwood Genetic Center

whole genome sequencing

copy number variations

rare hereditary diseases

Illumina TruSeq Nano DNA Library Prep Kit

Illumina NovaSeqTM 6000 System

microarray-based testing

Mendelian diseases

Affymetrix CytoScan HD/XON Microarray Platform

Sanger sequencing