Navigation Links
Sequencing works in clinical setting to help -- finally -- get a diagnosis
Date:5/7/2012

DURHAM, N.C. -- Advanced high-speed gene-sequencing has been used in the clinical setting to find diagnoses for seven children out of a dozen who were experiencing developmental delays and congenital abnormalities for mysterious reasons.

"I thought if we could obtain even a couple of relatively secure diagnoses out of the 12 patients, that would prove the value of deploying sequencing approaches systematically in patients with unknown but apparently genetic conditions," said David Goldstein, Ph.D., director of the Duke Center for Human Genome Variation and professor of molecular genetics and microbiology.

"Few sequencing studies have approached the problem as we did, taking a very heterogeneous group of patients," Goldstein said. "Getting a likely diagnosis about half of the time is quite stunning and strongly motivates next-generation sequencing for all patients that fail to get a genetic diagnosis through traditional testing."

The research team used next-generation sequencing, a new technology that can rapidly read a person's entire genome or just their exome, the sections of DNA that make the proteins, which direct physiological activities. The cost of such sequencing is becoming lower, making it feasible to do the study in a clinical setting.

The work was published online on May 8, in the Journal of Medical Genetics.

"There are up to 50,000 live births in America each year with the children having features of developmental delays, intellectual disabilities or congenital abnormalities similar to those we studied," said Vandana Shashi, M.D., co-author and associate professor of pediatrics in the Duke Center for Human Genetics. "Many of these children remain without diagnoses and we could systematically try to help identify a cause."

Shashi said families involved with the study often expressed relief just to have a diagnosis, even when a condition remained difficult or impossible to treat.

"Just knowing what was causing the problem took away the mystery, which gives families some comfort," Shashi said.

Goldstein said that simply studying more patients with sequencing tools would facilitate discovery by searching for similarities among patients that have mutations in the same or similar genes.

With time, this would also reveal more diagnoses, said lead author Anna Need, Ph.D., who works in the Duke Center for Human Genome Variation.

"Despite the fact that we ended up with a short list of gene variants for each person we studied and ran other tests, we had no real evidence of a related disease because there haven't been other reported conditions or people with mutations in those genes," Need said. "Some of the people we had no results for yet may get answers as their variants become associated with diseases through other sequencing."

The results of this study also are important for genetic counseling, Goldstein said.

For example, some of the likely diagnoses are due to new mutations that happened in the children, known as de novo mutations. In these cases, the parents would be less likely to pass it on through a subsequent pregnancy, for example.

Another lesson of the study was that some of these individuals may have multiple genetic conditions. Shashi noted one child received a diagnosis for only one of several conditions she had.

"We may not find all of the genetic causes, but over time the success of this type of testing and the information we learn will only grow," Need said. "Out of the genes we found, two have been found to be associated with disease through recent studies by other researchers."

Goldstein said it is imperative to set up large genetic databases in tertiary medical centers, which have the doctors and scientists who can evaluate patients who might benefit from next-generation sequencing. They would also have the team to do the genomic sequencing, and then, to follow up with biological tests that show the function of the gene.

Goldstein said that hospitals with the right systems in place can note a patient's clinical features and then examine a patient's cells or do a relatively general protein localization assay in cells to get an idea about gene function.

"This is a generalized follow-up system for any of the candidate genes, and the work can be done at a tertiary hospital center for virtually any candidate gene, but not by the diagnostic companies, which don't do any functional testing," Goldstein said. "That's why I see a role for this effort being grounded in an academic research environment."


'/>"/>
Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

Related biology news :

1. Powerful sequencing technology decodes DNA folding pattern
2. Analyzing complex plant genomes with the newest next-generation DNA sequencing techniques
3. Genome sequencing finds unknown cause of epilepsy
4. Chinese scientists announce the first complete sequencing of Mongolian genome
5. Brigham and Womens Hospital awarded $9.6 million to study whole genome sequencing
6. BGI and CIAT announce collaboration for large-scale genome sequencing of cassava
7. Biotech start-up brings DNA-sequencing to the medical market
8. Forest Service part of team sequencing 1,000 fungal genomes
9. Trillions served: Massive, complex projects for DOE JGI 2012 Community Sequencing Program
10. Liver parasite lacks key genes for fatty acid synthesis: Genome sequencing of Clonorchis sinensis
11. Scripps launches whole genome sequencing study to find root causes of idiopathic diseases
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/19/2016)... , UAE, April 20, 2016 ... implemented as a compact web-based "all-in-one" system solution for ... biometric fingerprint reader or the door interface with integration ... modern access control systems. The minimal dimensions of the ... readers into the building installations offer considerable freedom of ...
(Date:4/14/2016)... 14, 2016 BioCatch ™, ... today announced the appointment of Eyal Goldwerger ... Goldwerger,s leadership appointment comes at a time ... the deployment of its platform at several of the ... which discerns unique cognitive and physiological factors, is a ...
(Date:3/31/2016)... , March 31, 2016  Genomics firm Nabsys ... founding CEO, Barrett Bready , M.D., who returned ... of the original technical leadership team, including Chief Technology ... of Product Development, Steve Nurnberg and Vice President of ... to the company. Dr. Bready served as ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... June 27, 2016 , ... Newly created ... services and solutions to the healthcare market. The company's primary focus is on ... sales and marketing strategies that are necessary to help companies efficiently bring their ...
(Date:6/24/2016)... , June 24, 2016 Epic ... sensitively detects cancers susceptible to PARP inhibitors by ... tumor cells (CTCs). The new test has already ... therapeutics in multiple cancer types. Over ... DNA damage response pathways, including PARP, ATM, ATR, ...
(Date:6/23/2016)... 23, 2016   Boston Biomedical , an ... designed to target cancer stemness pathways, announced that ... Orphan Drug Designation from the U.S. Food and ... cancer, including gastroesophageal junction (GEJ) cancer. Napabucasin is ... inhibit cancer stemness pathways by targeting STAT3, and ...
(Date:6/23/2016)... -- The Prostate Cancer Foundation (PCF) is pleased to announce 24 new ... prostate cancer. Members of the Class of 2016 were selected from a pool ... Read More About the Class of 2016 PCF Young Investigators ... ... ...
Breaking Biology Technology: