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Glenn Nichols, surrounded by his hospice team. The author is in yellow.

Genetic Linkage

Why I Don't Want to Know My Genome Sequence

November 2, 2012

Tags: exome, genome, human genome project, Craig Venter, James Watson, Ozzy Osbourne, Francis Collins

Even after writing 10 editions of a human genetics textbook, I don't want to know my genome sequence. Yet.
Famous folk have been writing about their genome sequences for a few years now. But when I received two such reports at once last week – about genetics researcher Ron Crystal, MD, and a hypothetical (I think) story about President Obama, I knew it was time to take action.

Or, in my case, inaction. (more…)

The Crime Gene Revisited

January 27, 2012

Tags: XYY, crime gene, Patricia Jacobs, GWAS, Ricki Lewis, congenital criminals, genetic determinism, National Longitudinal Study of Adolescent Health, human genome project, Law and Order, twin study, heritability, Jeffrey Dahmer, Back to the Future, Marty McFly

"Research shows genes influence criminal behavior," proclaims a January 25 news release, setting my genetic determinism detector on high alert.

I flashed back to the cover of the May 18, 1970 Newsweek, “Congenital Criminals?” which probed the work of Patricia Jacobs. Here’s what my human genetics textbook says on the study provoking the 1970 headline: (more…)

Ricki’s Rant: Genome Sequence, NOT Genetic Code

January 11, 2012

Tags: genetic code, human genetics, human genome sequence, human genome project, Ricki Lewis, Morse code, computer code, Wall Street Journal, National Geographic, insulin, X-Files, model organisms, drug discovery, recombinant DNA, viruses

Strawberries can use a gene from peanuts to withstand frost because the genetic code is universal.
Humans do not have their own genetic code, and certainly each of us does not have his or her own. The idea of our utter uniqueness might be attractive, but genetics just doesn’t work that way. And it’s a good thing.

The genetic code is the correspondence between a unit of DNA (more…)

Genetic Incidentalomas

June 12, 2011

Tags: spinal muscular atrophy, SMA, direct-to-consumer genetic testing, genetic counseling, Tay-Sachs disease, bioethics, 23andMe, Ricki Lewis, incidentaloma, human genome project, personal genome sequencing, copy number variants, CNVs, Families of SMA, SMA Treatment Acceleration Act, GeneTests.org

Brandon Alspaugh is worried. He’s an interventional radiologic technologist at South University in Charlotte, NC, taking human genetics in preparation for physician’s assistant school. When he got to the end of my textbook, where I ask students to e-mail me their concerns, he wrote the following:

“Dr. Lewis,

Coming from the medical field, I worry that personal genomics, while useful in terms of screening for genetic disease, will come to have the same effect as full-body CT scans, where the amount of noisy data generated will drown out the important bits. As with atypical anatomy, a person might spend a month chasing down a suspicious allele only to find it's a normal variant of a beneficial gene.”

Brandon’s describing a new breed of incidentaloma, looking for one sign of abnormality that turns up what could be another. I went in for a CT scan of my lungs, for example, and the doctor fretted over my polycystic liver. A friend had it much worse. She volunteered to be a control in an Alzheimer’s imaging trial, and her scan revealed two brain aneurysms!

The term “incidentaloma” was coined to describe an adrenal tumor (hence the "oma") found on a scan looking for something else. More recently, incidentalomas are arising as collateral damage from the sequencing of the human genome and the genetic testing it has spawned. We now have too much information, and too few people (genetic counselors) to translate what we do know.

The founding fathers (there were no mothers in the famed “amino acid club”) who deciphered the genetic code back in the 1960s would not have predicted genetic incidentalomas; surely all DNA was translated into protein. Over the years, the percentage fell, precipitously, so that now we know (or suspect) that a mere smidge under 2% of the genome actually encodes proteins – a little like a John Grisham novel in which much of the story turns out to be, if not irrelevant, then not central to the main story.

Genetics is about variation, not just disease, and I fear that because of this, a direct-to-consumer genetic testing company, anxious to spew as much information as possible at its clientele, could indeed impart a sequence or two that is innocuous, as Brandon the astute student suggests. And genetic incidentaloma-ism extends to well known protein-encoding genes. I saw this the day after I heard from Brandon, when a nurse-midwife at the practice where I provide genetic counseling called me, alarmed at a lab result for a patient.

“What’s SMN? The blood test results came back with a risk of 1 in 632 for SMA, based on SMN copy number. What’s that?”

If the nurse-midwife didn’t recognize it (and why would she?), I feared, the patient certainly wouldn’t. And so I explained that SMN is the gene “survival motor neuron” and various versions of it are implicated in the most common type of spinal muscular atrophy (SMA),a recessive disease in the same general incidence ballpark as cystic fibrosis – 1 in 38 of us is a carrier. (I elected not to get into copy number variants, a recently-recognized form of mutation.)

I knew that more widespread testing for SMA was beginning because of pending legislation (The SMA Treatment Acceleration Act) “to authorize the Secretary of Health and Human Services to conduct activities to rapidly advance treatments for spinal muscular atrophy, neuromuscular disease, and other pediatric diseases, and for other purposes.” Some three dozen labs offer carrier testing at GeneTests.org.

I also knew about SMA from a young hospice patient I’d visited in a nursing home. She was 7, a long-term survivor for this disease known as “baby ALS" that is usually fatal by age 3. (Also see Families of SMA.)

So should the midwife tell the patient, who must have signed something but likely has no idea her blood was tested for SMA, her carrier risk? Would the patient understand that the test indicates her risk is well BELOW that of the average person for something that she probably doesn't know exists? Does alerting and possibly alarming many people justify the additional SMA cases that screening might prevent by detecting potential parents who are both carriers? After all, this is the approach that has nearly vanquished Tay-Sachs disease. (See A Brief History of Genetic Testing.)

A slippery slope looms.

How far are we from personal genome scans that yield long lists of risks, some meaningful, some not? Who will develop the criteria for what is meaningful, for what a patient should know? Should a health care practitioner disclose ALL genetic information so as not to be paternalistic, or shield the patient from test results to “do no harm?” What happens when a genetic risk identified today declines with a future discovery? (Not everyone taps into 23andMe on a daily basis to check for updates.) Or should a patient indeed be told absolutely everything, in case there is something he or she can do, environmentally speaking, to alter genetic destiny?

As with all matters scientific, the more we learn, the more we find out that we don’t know. It will be interesting to see how the impending avalanche of genetic incidentalomas plays out.

instruction
Project to engage students in helping families with rare genetic diseases
Book Club Reader's Guide
Many challenging questions to stimulate thought and discussion.
Instructor's Guide
38 discussion questions to get students thinking and talking about gene therapy, including the science, ethical issues, and the drug approval process.
Narrative science
The Forever Fix is the uplifting true story of 8-year-old Corey Haas, who was cured of hereditary blindness just 4 days after gene therapy.
College Textbooks
A spectacularly-illustrated, clearly written human anatomy and physiology textbook, used in pre-health profession programs throughout the U.S.
A highly engaging, clearly written, beautifully illustrated introduction to the science of human genetics for the non-scientist. Now in its 11th edition, 12th to be published in September 2018.
Nonfiction
An ideal starting point for anyone who wants to know more about genes, DNA, genomes, and the genetic ties that bind us all.

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