We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Trial Finds High Analytical Performance in Whole-Genome Sequencing

By LabMedica International staff writers
Posted on 26 Oct 2019
Genetic diseases are a leading cause of infant mortality particularly among infants admitted to neonatal, pediatric, and cardiovascular intensive care units (ICUs). More...
Disease progression can be extremely rapid in infants, necessitating early etiologic diagnosis in order to inform interventions that can lessen suffering, morbidity, and mortality.

Timely diagnosis requires genome-scale testing since more than 14,000 simple genetic diseases have been described and their presentations often overlap in seriously ill infants. Examples include seizures, respiratory and cardiac failure, hypotonia, hypoglycemia, and jaundice. Whole-genome sequencing can be a viable first-line diagnostic testing option, according to a recent trial.

Scientists at the Rady Children's Institute for Genomic Medicine (San Diego, CA, USA) sought to enroll a greater range of infants, as compared to previous efforts. In the past, clinical sequencing studies focused on infants in intensive care units with unknown, but suspected genetic diseases. Here, the team used broader inclusion criteria, but did, for instance, exclude infants for whom it was thought unlikely that a genetic diagnosis would change their clinical management or who had sepsis but were responding to therapy normally. In all, 213 infants were enrolled in the study.

Eleven percent of these infants were too ill to undergo randomization and instead received ultra-rapid whole-genome sequencing, as that approach would provide the fastest possible route to diagnosis. Of the remaining 189 infants, 95 were randomized to receive whole-exome sequencing and 94 to whole-genome sequencing. They underwent sequencing within 96 hours of their admission to the neonatal ICU (NICU).

Trio EDTA-blood samples were obtained where possible and all samples were sequenced upon receipt. Genomic DNA was isolated with an EZ1 Advanced XL robot and the EZ1 DSP DNA Blood kit. DNA quality was assessed with an assay kit using the Gemini EM Microplate Reader. Genomic DNA was fragmented by sonication, and bar-coded, paired-end, PCR-free libraries were prepared for rWGS with TruSeq DNA LT kits or Hyper kits.

Both whole-genome and whole-exome sequencing had similar diagnostic rates, 19% and 20%, respectively. The time to diagnosis was also similar for the two groups, about 12 days. However, the scientists contended that the difference in the proportion of diseases diagnosed by whole-exome and whole-genome sequencing will likely change as experts' ability to interpret the pathogenicity of noncoding and structural variation improves. As it stands now, interpretation is largely confined to coding variation. Ultra-rapid whole-genome sequencing (urWGS) meanwhile, had a diagnostic rate of 46% and a median time to diagnosis of 2.3 days, which indicated to the investigators that it could be valuable as a first-tier test.

The authors concluded that rapid genomic sequencing can be performed as a first-tier diagnostic test in infants with diseases of unknown etiology at time of admission to regional ICUs. In unstable infants and those in whom a genetic diagnosis was likely to impact immediate management, urWGS had optimal analytic and diagnostic performance, by virtue of shortest time to result. The study was published on October 3, 2019, in the American Journal of Human Genetics.

Related Links:
Rady Children's Institute for Genomic Medicine


New
Gold Member
Blood Gas Analyzer
Stat Profile pHOx
3-Part Differential Hematology Analyzer
Swelab Alfa Plus Sampler
New
Clostridium Difficile Toxin A+B Combo Card Test
CerTest Clostridium Difficile Toxin A+B
New
Staining System
RAL DIFF-QUIK
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








Channels

Hematology

view channel
Image: CitoCBC is the world first cartridge-based CBC to be granted CLIA Waived status by FDA (Photo courtesy of CytoChip)

Disposable Cartridge-Based Test Delivers Rapid and Accurate CBC Results

Complete Blood Count (CBC) is one of the most commonly ordered lab tests, crucial for diagnosing diseases, monitoring therapies, and conducting routine health screenings. However, more than 90% of physician... Read more

Immunology

view channel
Image: A simple blood test could replace surgical biopsies for early detecion of heart transplant rejection (Photo courtesy of Shutterstock)

Blood Test Detects Organ Rejection in Heart Transplant Patients

Following a heart transplant, patients are required to undergo surgical biopsies so that physicians can assess the possibility of organ rejection. Rejection happens when the recipient’s immune system identifies... Read more

Pathology

view channel
These images illustrate how precision oncology Organ Chips recapitulate individual patients’ responses to chemotherapy (Photo courtesy of Wyss Institute at Harvard University)

Cancer Chip Accurately Predicts Patient-Specific Chemotherapy Response

Esophageal adenocarcinoma (EAC), one of the two primary types of esophageal cancer, ranks as the sixth leading cause of cancer-related deaths worldwide and currently lacks effective targeted therapies.... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.