domingo, 8 de abril de 2012

Genome sequencing to add new twist to doctor-patient talks -

Genome sequencing to add new twist to doctor-patient talks -

Genome sequencing to add new twist to doctor-patient talks

Ethical questions need to be answered, including what genetic findings should be reported to patients.

By Christine S. Moyer, amednews staff. Posted April 2, 2012.

New York geneticist Robert Marion, MD, envisions a future where whole-genome sequencing will be used to help prevent many medical conditions from developing.
Geneticists say this new era of medicine could occur within a decade, thanks to the complicated procedure being tested in a growing number of research settings across the country.
In whole-genome sequencing, geneticists use a patient’s blood sample or other source of genetic material to examine the 20,000 to 25,000 genes that make up an individual’s genome. By comparison, standard genetic testing used widely by health professionals today examines only individual genes, geneticists say. As a result, physicians often must order multiple tests to get needed genetic information.
Whole-genome sequencing will enable specialists to identify variations in a person’s genetic code that increase his or her genetic risk of developing a spectrum of conditions, including Alzheimer’s disease, cancer, diabetes and schizophrenia. The procedure also will reveal the cause of undiagnosed symptoms, an individual’s propensity for becoming dependant on nicotine, and the likely effect of medication on conditions such as asthma and cardiovascular disease.
Some geneticists estimate that within five years, as the procedure becomes more affordable, primary care physicians will begin sifting through patients’ whole-genome sequence results and creating preventive care plans for conditions the individual is at risk of developing. In 10 years, such sequencing could become a routine part of medical care performed on newborn babies and older patients.
An estimated 20,000 to 25,000 genes make up a person’s genome.
“Medicine will go from a field where we are reactive to one in which we can prevent symptoms and signs from ever occurring. That’s really a game-changer in medicine,” said Dr. Marion, chief of the division of genetics and child development in the Dept. of Pediatrics at the Children’s Hospital at Montefiore and the Albert Einstein College of Medicine in New York.
But these experts admit there are uncertainties and ethical concerns about whole-genome sequencing that need to be resolved before it becomes a standard procedure used by physicians for patients. Among the chief worries is what to do with the large number of variants in genes associated with human disease that can show up in a patient’s sequencing.
“The genome is so complex and some of our understanding of various mutations is so shaky that it’s hard to tell which information is meaningful and which isn’t,” said Robert C. Green, MD, MPH, associate professor of medicine in the Division of Genetics at Brigham and Women’s Hospital and Harvard Medical School in Boston.
There are no guidelines on which findings from whole-genome sequencing geneticists should report to physicians and which results should be passed on to patients, geneticists say. Also lacking is clear guidance on who should have access to the findings, such as a patient’s employer or relatives who could share some of the same genes.
“The ethics of this has to be worked out, but this is what usually happens in molecular genetics and technology in general,” Dr. Marion said. “This will alter the way we care for people.”

Telling patients genetic predispositions

The human genome contains about 3 billion DNA base pairs, which are the chemical building blocks that form the two DNA strands. About 3 million such bases vary from one individual to the next, said Paul R. Billings, MD, PhD, an internist and clinical geneticist in Carlsbad, Calif. He also is chief medical officer of the California-based Life Technologies Corp., which develops biotechnology products and services for research and clinical applications.
He said most of those variations do not affect a person’s health. But some indicate a medical risk. In those cases, physicians will have to determine which risks to report to patients.
The human genome contains about 3 billion DNA base pairs.
Some geneticists contend that giving patients all of the findings could overwhelm them and lead to unnecessary anxiety, medical tests and procedures. Others, including Dr. Billings, say patients deserve access to their whole-genome sequencing results as long as those results are put into perspective and delivered in a sensitive manner.
There also is concern about whether genetic experts who assess a patient’s whole genome should disclose all of the findings to the individual’s physician.
In a recent study, 16 clinical geneticists and/or molecular laboratory directors unanimously agreed on disclosing to physicians known pathogenic mutations for 21 of 99 possible conditions if they were found incidentally in adults. The experts unanimously agreed on reporting pathogenic mutations for four conditions if found in children, according to the study published online March 15 in Genetics in Medicine.
Incidental findings were defined as results unrelated to the reason whole-genome sequencing was ordered. The surveyed genetic experts agreed to disclose mutations of genes such as those for hereditary breast cancer and ovarian cancer in adults and retinoblastoma in children.
The philosophical question is “whether information should be shared with clinicians when we have a very limited understanding of what [some of] the information means,” said Dr. Green, the lead study author.
Whatever information primary care physicians receive, they will use the sequencing results to develop personalized, preventive care plans for a patient.
About 3 million DNA base pairs vary from one individual to the next.
Geneticists say physicians will not take on this task alone. Instead, a team of doctors, geneticists, genetic counselors and possibly social workers will counsel patients before and after sequencing, they say. Explaining results to patients also will be a team effort due to the complexity of the information.
Elwyn, Pa.-based genetic counselor Brenda Finucane regularly works with doctors who order standard genetic tests for patients. These tests often are used to help identify the cause of children’s developmental delays and to detect one’s risk of developing a disease such as breast cancer, said Finucane, president of the National Society of Genetic Counselors. She discusses with patients how the test works and what types of health findings it might uncover.
A challenge she foresees with whole-genome sequencing is how to prepare patients for the possibility of receiving pages listing health conditions they are at risk of developing.
Geneticist Charis Eng, MD, PhD, said health professionals could use a patient’s family history to help determine which results to provide to the individual. For example, if a patient’s family history predisposes the patient to diabetes and breast cancer, Dr. Eng suggests telling the individual, “We will only look at the breast cancer genes and the diabetes genes. We’re not going to look at anything else.”
But some patients may want to see results for all the genes that could impact their health, said Dr. Eng, professor and founding chair of the Genomic Medicine Institute. She also is founding director of the Center for Personalized Healthcare at Cleveland Clinic.
Health professionals will need to make clear to patients that a genetic predisposition to a disease doesn’t mean that a patient will die of that disease, Dr. Eng said. In fact, she said physicians could tell patients, “We absolutely know how to prevent this.”
By creating personalized treatment plans that target factors such as diet and exercise, doctors will be able to keep symptoms of many conditions from appearing.
“Imagine how powerful that will be,” Dr. Eng said.

Addressing the ethics of sequencing

Bioethicist Jeffrey Kahn, PhD, MPH, said it will be important for the health care community to keep patients’ whole-genome sequencing results private. But patients probably will need to tell relatives about genetic variations, such as a mutation in the breast cancer gene, that could impact those family members.
The Genetic Information Nondiscrimination Act of 2008 prevents discrimination by health insurers and employers of people who have known genetic variations that might impact their health. There also have been recent discussions about whether the Americans with Disabilities Act provides some workplace protection for people with a known genetic predisposition for a medical condition, said Kahn, professor of bioethics and public policy at Johns Hopkins Berman Institute of Bioethics in Baltimore.
American Medical Association policy says genomic-based personalized medicine will play an increasingly important role in patient care. The Association is developing educational resources and point-of-care tools to help doctors implement genomic-based medicine.
“Primary care physicians should know that genomics is coming,” said Dr. Green, of Brigham and Women’s Hospital. “It will be part of their practices.”


The 21 genetic conditions that should be reported to doctors

There are no established guidelines on which genetic variants should be presented to physicians as incidental findings from whole-genome sequencing. A recent study showed that genetic specialists agreed that pathogenic mutations for 21 common genetic conditions should be disclosed.


  • APC-associated polyposis
  • Fabry disease
  • Familial hypercholesterolemia
  • Galactosemia
  • Gaucher disease
  • Glycogen storage disease type IA
  • Hereditary breast and ovarian cancer
  • Homocystinuria
  • Li-Fraumeni syndrome
  • Lynch syndrome
  • Multiple endocrine neoplasia type 1
  • Multiple endocrine neoplasia type 2
  • MYH-associated polyposis
  • Phenylketonuria
  • Pompe disease
  • PTEN hamartoma tumor syndrome
  • Retinoblastoma
  • Romano-Ward (long QT syndrome)
  • Tyrosinemia type 1
  • Von Hippel-Lindau disease
  • Wilson disease


  • PTEN hamartoma tumor syndrome
  • Retinoblastoma
  • Romano-Ward (long QT syndrome)
  • Von Hippel-Lindau disease
Source: “Exploring concordance and discordance for return of incidental findings from clinical sequencing,” Genetics in Medicine, published online March 15 (


“Exploring concordance and discordance for return of incidental findings from clinical sequencing,” Genetics in Medicine, published online March 15 (
National Human Genome Research Institute (
Centers for Disease Control and Prevention on public health genomics (

Copyright 2012 American Medical Association. All rights reserved.

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