A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018, University of Utah
Sean Tavtigian, PhD, a cancer researcher at Huntsman Cancer Institute (HCI) and professor of oncological sciences at the University of Utah. Credit: Huntsman Cancer Institute

Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

The research was led by Sean Tavtigian, PhD, a cancer researcher at Huntsman Cancer Institute (HCI) and professor of at the University of Utah, in collaboration with genetics experts from around the United States.

Tavtigian utilized Bayes' Theorem, a math equation first published in 1763, as the basis of a he and the team developed to assess the rigor of the current, widely-used approach to evaluate the results of a clinical genetic test.

Clinical genetic testing is used in a variety of medical fields, including cancer care, obstetrics, and neurosciences, among others. Results of a genetic test may help to provide a definitive medical diagnosis, or assess the likelihood of a person to develop a particular disease before symptoms appear. The range of approaches employed to provide health care based on the results of the test can vary significantly. Patients may be at negligible risk for disease with no required, or they may pursue costly, invasive medical treatment in an effort to stave off disease or manage and minimize symptoms.

With millions and millions of changes possible in genes that control health in any given person, the challenge of discerning which gene changes are likely to cause disease is vast. In the past few years, human genetic researchers have identified thousands of Variants of Uncertain Significance (VUS), that is, genetic changes without a known understanding of how they may impact a person's health. "A large fraction of VUS are believed to be generally harmless," describes Tavtigian. "One only wants to change the medical management of patients when the genetic testing identifies a variant that is likely to be disease-causing. Against a huge population of harmless VUS, how do you identify the small subset that are likely to require medical management?"

The research team set out to reduce subjectivity or interpretation bias in the review of genetic results to determine whether a patient is susceptible to . Using the computational tool they designed, they tested 18 subjective rules recommended by the American College of Genetics and Genomics (ACMG) in the current framework for assessing results of clinical genetic tests. They found that the ACMG's system of 18 rules is statistically sound and that the rules are objectively strong. Also, the rules generally maintained their relative strength when tested against one another. Further, the team explored ways to allow the framework to continue to be employed as new findings about genetics are added to this body of knowledge.

"The scale of genetic testing used by specialists is growing exponentially, with genetic testing laboratories working to keep up with the demands of processing and interpreting the results of genetic tests," says Tavtigian. "The points of internal consistency that we found did not have to be true—yet they are, and it is important that the community knows this. We hope this work will help accelerate application of results from these tests to make decisions about patient care, adding years to patient's lives."

Explore further: Concerns surround use of direct-to-consumer genetic testing

More information: Sean V Tavtigian et al, Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework, Genetics In Medicine (2018). DOI: 10.1038/gim.2017.210

Related Stories

Concerns surround use of direct-to-consumer genetic testing

October 27, 2017
(HealthDay)—Direct-to-consumer genetic testing raises unique concerns and considerations, according to a committee opinion published online Oct. 24 in Obstetrics & Gynecology.

Genomic data sharing is critical to improving genetic health care

January 5, 2017
There are an estimated 5,000 - 7,000 rare genetic diseases, each of which can vary dramatically and be caused by a multitude of different genetic changes. Even common diseases with genetic influences may also have rare variants ...

Recommendations for genetic counseling and genetic testing for hereditary prostate cancer

December 13, 2017
To date, there have been few recommendations to guide physicians about when to offer men genetic consultation for prostate cancer risk. Now, an international and inter-specialty panel of experts convened at the Sidney Kimmel ...

Internists play a vital role in identifying patients for genetic counseling for cancer risk

October 30, 2017
Patients at high risk for familial cancer, history of cancer at a young age, or history of multiple cancer occurrences may be referred to genetic counseling for genetic testing from the primary care office, which makes internists ...

Physicians' misunderstanding of genetic test results may hamper mastectomy decisions

April 12, 2017
A recent survey of over 2,000 women newly diagnosed with breast cancer found that half of those who undergo bilateral mastectomy after genetic testing don't actually have mutations known to confer increased risk of additional ...

CONNECT registry shows only 9 percent compliance with genetic testing guidelines for AML

June 5, 2017
Guidelines by the National Comprehensive Cancer Network (NCCN) recommend testing for seven known genetic changes in patients with Acute Myeloid Leukemia (AML). A study presented today at the American Society for Clinical ...

Recommended for you

Psychiatric disorders share an underlying genetic basis

June 21, 2018
Psychiatric disorders such as schizophrenia and bipolar disorder often run in families. In a new international collaboration, researchers explored the genetic connections between these and other disorders of the brain at ...

Deep data dive helps predict cerebral palsy

June 21, 2018
When University of Delaware molecular biologist Adam Marsh was studying the DNA of worms living in Antarctica's frigid seas to understand how the organisms managed to survive—and thrive—in the extremely harsh polar environment, ...

Genetic variation in progesterone receptor tied to prematurity risk, study finds

June 21, 2018
Humans have unexpectedly high genetic variation in the receptor for a key pregnancy-maintaining hormone, according to research led by scientists at the Stanford University School of Medicine. The finding may help explain ...

Shared genetics may shape treatment options for certain brain disorders

June 20, 2018
Symptoms of schizophrenia and bipolar disorder, including psychosis, depression and manic behavior, have both shared and distinguishing genetic factors, an international consortium led by researchers from Vanderbilt University ...

Scientists unravel DNA code behind rare neurologic disease

June 20, 2018
Scientists conducting one of the largest full DNA analyses of a rare disease have identified a gene mutation associated with a perplexing brain condition that blinds and paralyzes patients.

Simple sugar delays neurodegeneration caused by enzyme deficiency

June 20, 2018
A new therapeutic approach may one day delay neurodegeneration typical of a disease called mucopolysaccharidoses IIIB (MPS IIIB). Neurodegeneration in this condition results from the abnormal accumulation of essential cellular ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.