Whole genome sequencing of de novo balanced rearrangements in prenatal diagnosis
Whole genome sequencing of the DNA code of three prenatal samples provided a detailed map of the locations of their chromosomal abnormalities in 14 days, scientists reported today at the American Society of Human Genetics (ASHG) 2012 meeting in San Francisco.
"Such a relatively brief timeframe will enable physicians to predict diagnosis of serious congenital disorders prenatally to counsel the parents and plan perinatal care of infants with chromosomal rearrangements," said Zehra Ordulu, M.D., Brigham and Women's Hospital and Harvard Medical School medical research fellow in obstetrics, gynecology and reproductive biology, who presented the study.
In the study, whole genome sequencing was used after current prenatal diagnostic methods of karyotyping and array comparative genomic hybridization (aCGH) to provide nucleotide level precision were conducted.
Karyotyping and aCGH studies of the prenatal samples provided the first clues of "balanced de novo chromosomal rearrangements," and prompted the investigation by genomic sequencing.
Clinical consequences of such chromosome rearrangements, which are defined as the relocation of chromosome segments without any loss or gain in genomic material, are rare, not inherited and challenging to predict without knowledge of the precise breakpoints.
"Unlike karyotyping, aCGH and other standard methods, whole genome sequencing provided the information to detect the 'breakpoints" in the chromosomes at which the rearrangements occurred and thereby to determine the genomic regions altered," said Cynthia C. Morton, Ph.D., William Lambert Richardson Professor in obstetrics, gynecology and reproductive biology, professor of pathology at Brigham and Women's Hospital and Harvard Medical School and incoming president-elect of ASHG.
"Early detection of a genetic disorder is of significant importance for informing genetic counseling and for managing the pregnancy, birth and further clinical follow-up," said Dr. Morton, who headed the study.
"This study foretells an empowered prenatal diagnostic environment in which DNA sequencing becomes the standard of care," she added.
Dr. Ordulu also added, "Next-gen whole-genome sequencing in prenatal diagnosis for chromosomal rearrangements offers an unparalleled high resolution test for diagnosis and management of genetic disorders."
By using whole genome sequencing, Drs. Morton, Ordulu and collaborators determined in a third trimester prenatal sample of the first case that CHD7, a causal gene in CHARGE syndrome, was disrupted.
"Whole genome sequencing was consistent with a diagnosis of CHARGE syndrome, which was not possible based on prenatal imaging and the other commonly used prenatal genetic testing methods. This diagnosis would have changed medical care from an initial plan to repair an isolated heart defect to management of a morbid condition requiring immediate assessment of breathing and feeding difficulties," said Dr. Ordulu.
In the second and third pregnancies, sequencing revealed a single disrupted gene. "Whole genome sequencing reassured the parents that a known genomic syndrome is not associated with the single disrupted gene and provided valuable additional information to the historical risk assessment of an untoward outcome," Dr. Ordulu said.
Provided by American Society of Human Genetics
- Study finds massively parallel sequencing can detect fetal aneuploidies, including Down syndrome Feb 10, 2012 | not rated yet | 0
- New prenatal genetic test is much more powerful at detecting fetal abnormalities Feb 09, 2012 | not rated yet | 0
- Prenatal whole genome sequencing: Just because we can, should we? Aug 10, 2012 | not rated yet | 0
- Microarray analysis improves prenatal diagnosis Nov 17, 2008 | not rated yet | 0
- Prenatal molecular diagnosis for tuberous sclerosis complex Mar 02, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease. ...
Genetics May 16, 2013 | not rated yet | 0
DNA databases might help identify victims of crime and human trafficking, but how do we safeguard the personal privacy of innocent victims and family members? A new report online May 15 in the Cell Press journal Trends in ...
Genetics May 15, 2013 | not rated yet | 0
A new study conducted by researchers at the Child Study Center at NYU Langone Medical Center found men diagnosed as children with attention-deficit/hyperactivity disorder (ADHD) were twice as likely to be obese in a 33-year ...
54 minutes ago | not rated yet | 0 |
New research from the University of Southampton has shown that blind and visually impaired people have the potential to use echolocation, similar to that used by bats and dolphins, to determine the location of an object.
10 minutes ago | not rated yet | 0 |
A novel vaccine study from South Dakota State University (SDSU) will headline the groundbreaking research that will be unveiled at the American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference ...
32 minutes ago | not rated yet | 0
Parkinson's disease (PD) is a degenerative neurological disorder marked by a progressive loss of motor control. Despite intensive research, there are currently no approved therapies that have been demonstrated to alter the ...
32 minutes ago | not rated yet | 0
Women are less likely than men to receive care in a trauma center after severe injury, according to a new study of almost 100,000 Canadian patients.
57 minutes ago | not rated yet | 0
Over the past few decades, neuroscientists have made much progress in mapping the brain by deciphering the functions of individual neurons that perform very specific tasks, such as recognizing the location ...
2 hours ago | 5 / 5 (3) | 0 |