Like Alvy Singer, Woody Allen’s character in Annie Hall, I’m obsessed with books about the end of humanity, which sometimes involves the end of the world, and sometimes just that of Homo sapiens. Midsummer is a good time to contemplate how bioethics would come into play in such unlikely scenarios, which raise issues of utilitarianism, justice, paternalism, death and dying, and misuse of technology. Read More
Genetic Linkage
Summer Reading for Bioethicists: End-of-the-World and Death Books
July 24, 2011
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"Dignity Therapy" Paper Ignores Hospice
July 10, 2011
”Dignity therapy" is a “novel psychotherapeutic approach” that gives patients with a 6-month life expectancy “an opportunity to reflect on things that matter most to them or that they would most want remembered.” In these days of medical experts such as Sarah Palin equating reimbursed end-of-life discussions to death panels killing granny, an outcomes evaluation of any such intervention is essential. Read More
Taking a Chance on Chantix
July 4, 2011
After 60+ years of smoking, my mother-in-law’s lungs were surely a toxic wasteland, yet nothing would make her quit. By the time that studies from the 1950s finally led to warning messages on cigarette packages in the 1960s, too many nicotine molecules had bombarded neuron receptors in her brain’s nucleus accumbens, for far too long. She, like millions of others, was hooked. Read More
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A Medical Manual from 1909
June 22, 2011
I discovered a treasure at a thrift store. For 89 cents, I bought “The People’s Common Sense Medical Adviser in Plain English or Medicine Simplified,” by Dr. R. V. Pierce, head of The Invalids’ Hotel and Surgical Institute in Buffalo, New York, circa 1909. In these days of WebMD and direct-to-consumer genetic testing, this peek into medical history is quite an eye opener.
The first part of the 1,000-page tome is eerily similar to the human anatomy and physiology textbooks I co-author. Some things don’t change much. The final section unveils an astonishing natural pharmacopeia, from various barks and roots, to pulverized rabbit testicles to cure older men suffering from erectile dysfunction, or perhaps the newly-named “low T.” In between are sections that are just odd.
Chapters cover hygiene, “mother and babe,” marriage, and my personal favorite, “self abuse.” “Statistics show that insanity is frequently caused by masturbation,” admonishes Dr. P., and it can be deadly. He rails against “criminal abortion,” which is “secretly practiced by women who desire to rid themselves of the evidence of immorality, and by those in wedlock who wish to avoid the care and responsibility of rearing offspring.” And the good doctor has ideas about race that echo back to Darwin. While genetic researchers today marvel at the diverse genomes of the Koisan of Namibia, Dr. P. equates them to baboons.
The Medical Adviser is just as telling for what it omits – cancer, for example – from a time when tuberculosis (“consumption”), smallpox, and various fevers were of far more concern. It teems with terms probably not uttered in decades, and new to me: erysipelas, quinsy, scrofula, and of course spermatorrhea, about which the esteemed author obsesses (more on that soon).
The book is festooned with marvelous illustrations and page after page of testimonials. Sexism is entrenched. While names and photographs accompany the musings of women with “female weakness,” “womb trouble,” and “nervous collapse,” complaints from men with the aforementioned spermatorrhea (“seminal weakness,” aka premature ejaculation, thanks to self abuse) are identified only by case numbers.
I think Dr. P. could have used a female co-author. Read More
The first part of the 1,000-page tome is eerily similar to the human anatomy and physiology textbooks I co-author. Some things don’t change much. The final section unveils an astonishing natural pharmacopeia, from various barks and roots, to pulverized rabbit testicles to cure older men suffering from erectile dysfunction, or perhaps the newly-named “low T.” In between are sections that are just odd.
Chapters cover hygiene, “mother and babe,” marriage, and my personal favorite, “self abuse.” “Statistics show that insanity is frequently caused by masturbation,” admonishes Dr. P., and it can be deadly. He rails against “criminal abortion,” which is “secretly practiced by women who desire to rid themselves of the evidence of immorality, and by those in wedlock who wish to avoid the care and responsibility of rearing offspring.” And the good doctor has ideas about race that echo back to Darwin. While genetic researchers today marvel at the diverse genomes of the Koisan of Namibia, Dr. P. equates them to baboons.
The Medical Adviser is just as telling for what it omits – cancer, for example – from a time when tuberculosis (“consumption”), smallpox, and various fevers were of far more concern. It teems with terms probably not uttered in decades, and new to me: erysipelas, quinsy, scrofula, and of course spermatorrhea, about which the esteemed author obsesses (more on that soon).
The book is festooned with marvelous illustrations and page after page of testimonials. Sexism is entrenched. While names and photographs accompany the musings of women with “female weakness,” “womb trouble,” and “nervous collapse,” complaints from men with the aforementioned spermatorrhea (“seminal weakness,” aka premature ejaculation, thanks to self abuse) are identified only by case numbers.
I think Dr. P. could have used a female co-author. Read More
Genetic Sense and Nonsense
June 20, 2011
Genetic Linkage connects new research findings, based on the wiring of my brain after years of writing a human genetics textbook and lots of articles. Here, the linking of sense and nonsense.
The excitement of genetic research these days is when genome sweeps of people sharing a disease reveal possible responsible genes. That’s what happened when researchers at the Perelman School of Medicine at the University of Pennsylvania looked at genomic landmarks among 1,114 brains from people who had died of progressive supranuclear palsy (PSP), a form of dementia that affects movement.
PSP is a “tauopathy,” in which the dark gummy protein tau, of Alzheimer’s fame, smothers the brain. Compared to unaffected brains, the PSP brains differ in three genome neighborhoods, harboring three new
candidate genes that make sense: one impairs brain cells’ abilities to untangle misfolded proteins, another boots misfolded proteins out of cells, and a third may help wrap brain cells in insulating myelin. New drug targets!
In genetics nonsense is important too. A nonsense mutation inserts a “stop” right smack in the middle of a gene, like a period in the middle of a sentence. It shortens the encoded protein, causing some 1800 diseases. Ignoring a nonsense mutation can restore function, like saving a sentence truncated by an errant period with a stroke of white-out. The idea isn’t new – researchers discovered that bacteria can read-through nonsense mutations in the 1960s, and that certain common antibiotics, such as gentamicin, enable cells to read-through nonsense. Those drugs may provide old-fashioned (cheap) treatments for genetic diseases such as Rett syndrome. Alas, early attempts at treating cystic fibrosis, hemophilia, and Duchenne muscular dystrophy by suppressing nonsense mutations didn’t work because the antibiotic doses necessary would be toxic.
Now Yi-Tao Yu and co-workers at the University of Rochester report in Nature that they have invented a way to mimic antibiotic-mediated nonsense suppression. They’ve used a synthetic RNA to chemically tweak nonsense codons so that they are instead read as bona fide amino acids, in essence altering the genetic code. So far this approach, dubbed RNA modification, works in a test tube. But carefully-directed nonsense suppression holds enormous promise for correcting many genetic diseases. Stay tuned! Read More
The excitement of genetic research these days is when genome sweeps of people sharing a disease reveal possible responsible genes. That’s what happened when researchers at the Perelman School of Medicine at the University of Pennsylvania looked at genomic landmarks among 1,114 brains from people who had died of progressive supranuclear palsy (PSP), a form of dementia that affects movement.
PSP is a “tauopathy,” in which the dark gummy protein tau, of Alzheimer’s fame, smothers the brain. Compared to unaffected brains, the PSP brains differ in three genome neighborhoods, harboring three new
candidate genes that make sense: one impairs brain cells’ abilities to untangle misfolded proteins, another boots misfolded proteins out of cells, and a third may help wrap brain cells in insulating myelin. New drug targets!
In genetics nonsense is important too. A nonsense mutation inserts a “stop” right smack in the middle of a gene, like a period in the middle of a sentence. It shortens the encoded protein, causing some 1800 diseases. Ignoring a nonsense mutation can restore function, like saving a sentence truncated by an errant period with a stroke of white-out. The idea isn’t new – researchers discovered that bacteria can read-through nonsense mutations in the 1960s, and that certain common antibiotics, such as gentamicin, enable cells to read-through nonsense. Those drugs may provide old-fashioned (cheap) treatments for genetic diseases such as Rett syndrome. Alas, early attempts at treating cystic fibrosis, hemophilia, and Duchenne muscular dystrophy by suppressing nonsense mutations didn’t work because the antibiotic doses necessary would be toxic.
Now Yi-Tao Yu and co-workers at the University of Rochester report in Nature that they have invented a way to mimic antibiotic-mediated nonsense suppression. They’ve used a synthetic RNA to chemically tweak nonsense codons so that they are instead read as bona fide amino acids, in essence altering the genetic code. So far this approach, dubbed RNA modification, works in a test tube. But carefully-directed nonsense suppression holds enormous promise for correcting many genetic diseases. Stay tuned! Read More
Genetic Incidentalomas
June 12, 2011
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. Read More
“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. Read More
I'm a DES Daughter
June 6, 2011
Early June marks the 30th anniversary of the reporting of the first AIDS cases, but it’s also an older medical anniversary – recognition that the drug diethylstilbestrol (DES) derailed development of the reproductive systems of a huge cohort of fetuses. I was one.
My mom, like millions of others, was handed “a vitamin” while pregnant with me in 1954, which in those days of medical paternalism, she never questioned. And so when I became a teenager, I began to drip, and was hauled off to the gyno. The verdict: Adenosis. The label: DES daughter. It was scary.
As an endocrine disrupter before the term was coined, DES, among other things, played havoc with the boundaries between tissues of the cervix, which prevented glands from vanishing on schedule. With the hormonal onslaught of adolescence, the errant glands went into overdrive. Fortunately, I didn’t have the otherwise rare cancer whose sudden appearance led to identifying the problem, as with AIDS. I also escaped the trademark DES small uterus, and my husband, a DES son, escaped XY-related problems. But my mom did die of breast cancer – another legacy of the “vitamin” thought to protect against pregnancy loss. And so far the DES Follow-up Study on the third generation – my three daughters – has revealed only a slight increase in ovarian cancer risk that is likely a statistical fluke awaiting larger numbers.
Pregnancy paternalism took years to dissipate. In 1981, my ob clearly knew something was amiss, but he said nothing. And so we were shocked at the on-time birth of daughter #1, who weighed less than the scraggliest chicken at the supermarket.
Then in the middle '80s I began providing genetic counseling at CareNet Medical Group in Schenectady, NY, founded by a wonderful ob/gyn, Hong Kyu Cheon, whose mother had been a midwife in Korea. When he retired, he handed the practice over to his daughter and daughter-in-law. Today CareNet is run by women. It's not that an XY ob/gyn can't be competent or caring, but there is something comforting, given what happened to my mother, about a woman-run practice.
And how things have changed! Patients now come into doctors offices already very informed, even naming specific drugs thanks to all the TV ads. My genetic counseling patients come armed with printouts describing their risks and possible tests, and sometimes even direct-to-consumer genetic test results. It is hard to imagine my mother's time, when she was expected to happily take anything the white-coated authority figure handed out. Read More
My mom, like millions of others, was handed “a vitamin” while pregnant with me in 1954, which in those days of medical paternalism, she never questioned. And so when I became a teenager, I began to drip, and was hauled off to the gyno. The verdict: Adenosis. The label: DES daughter. It was scary.
As an endocrine disrupter before the term was coined, DES, among other things, played havoc with the boundaries between tissues of the cervix, which prevented glands from vanishing on schedule. With the hormonal onslaught of adolescence, the errant glands went into overdrive. Fortunately, I didn’t have the otherwise rare cancer whose sudden appearance led to identifying the problem, as with AIDS. I also escaped the trademark DES small uterus, and my husband, a DES son, escaped XY-related problems. But my mom did die of breast cancer – another legacy of the “vitamin” thought to protect against pregnancy loss. And so far the DES Follow-up Study on the third generation – my three daughters – has revealed only a slight increase in ovarian cancer risk that is likely a statistical fluke awaiting larger numbers.
Pregnancy paternalism took years to dissipate. In 1981, my ob clearly knew something was amiss, but he said nothing. And so we were shocked at the on-time birth of daughter #1, who weighed less than the scraggliest chicken at the supermarket.
Then in the middle '80s I began providing genetic counseling at CareNet Medical Group in Schenectady, NY, founded by a wonderful ob/gyn, Hong Kyu Cheon, whose mother had been a midwife in Korea. When he retired, he handed the practice over to his daughter and daughter-in-law. Today CareNet is run by women. It's not that an XY ob/gyn can't be competent or caring, but there is something comforting, given what happened to my mother, about a woman-run practice.
And how things have changed! Patients now come into doctors offices already very informed, even naming specific drugs thanks to all the TV ads. My genetic counseling patients come armed with printouts describing their risks and possible tests, and sometimes even direct-to-consumer genetic test results. It is hard to imagine my mother's time, when she was expected to happily take anything the white-coated authority figure handed out. Read More
Fruit Flies Bring Good News to Huntington's Disease Families
June 2, 2011
I’m a big supporter of animal research, but I usually keep such studies out of my textbooks, because too many times what’s true for a mouse turns out not to be true for a person. But the news from Flav Giorgini and colleagues at the University of Leicester, University of Maryland School of Medicine, and Gladstone Institutes in San Francisco is hard to ignore – and it isn’t even in mice, but my old pals fruit flies.
The science is straightforward: blocking production of an enzyme called KMO, either by knocking out its gene or feeding flies drug-laced goop, enables flies with a version of Huntington’s disease to move more normally. HD is the neurodegenerative disease that struck Woody Guthrie, causing uncontrollable, dancelike movements. Dr. Giorgini discovered the connection to KMO in yeast in 2005, using resistance against cell death as a sign, since yeast are not known to dance. And the next step is obvious – try KMO inhibitors in people. The enzyme is also implicated in Alzheimer’s disease, ALS, AIDS dementia, and a host of other common conditions.
This fly/KMO study is a perfect example of the value of animal research. And so I went onto the People for the Ethical Treatment of Animals website to see what they had to say about the value of fruit fly research. Flies are, after all, animals. I found only an outdated blog comment about a PETA-provided bug catcher, which one would presumably use to escort errant cockroaches outside. The main page featured, as usual, the adorable – dogs, monkeys, and lions – and if you search a bit, the occasional mistreated turkey or lobster. The Bambi factor is at work - protect the furry.
I'm relieved. As a former Drosophila geneticist and author of fly porn, I personally murdered millions of the little beasts, heartlessly drowning them in vats of mineral oil, or exploding their innards when I drank too much coffee before injecting them. Since then, I've lived in fear of attack by Alicia Silverstone. I guess I can keep my American Physiological Society “I’m Alive! Thanks to Animal Research!” tee shirt. Read More
The science is straightforward: blocking production of an enzyme called KMO, either by knocking out its gene or feeding flies drug-laced goop, enables flies with a version of Huntington’s disease to move more normally. HD is the neurodegenerative disease that struck Woody Guthrie, causing uncontrollable, dancelike movements. Dr. Giorgini discovered the connection to KMO in yeast in 2005, using resistance against cell death as a sign, since yeast are not known to dance. And the next step is obvious – try KMO inhibitors in people. The enzyme is also implicated in Alzheimer’s disease, ALS, AIDS dementia, and a host of other common conditions.
This fly/KMO study is a perfect example of the value of animal research. And so I went onto the People for the Ethical Treatment of Animals website to see what they had to say about the value of fruit fly research. Flies are, after all, animals. I found only an outdated blog comment about a PETA-provided bug catcher, which one would presumably use to escort errant cockroaches outside. The main page featured, as usual, the adorable – dogs, monkeys, and lions – and if you search a bit, the occasional mistreated turkey or lobster. The Bambi factor is at work - protect the furry.
I'm relieved. As a former Drosophila geneticist and author of fly porn, I personally murdered millions of the little beasts, heartlessly drowning them in vats of mineral oil, or exploding their innards when I drank too much coffee before injecting them. Since then, I've lived in fear of attack by Alicia Silverstone. I guess I can keep my American Physiological Society “I’m Alive! Thanks to Animal Research!” tee shirt. Read More
Blaming Genes in the Workplace
May 25, 2011
Think it’s a great idea to send off a spit sample to see which future health conditions lurk in your DNA? In the U.S., the Genetic Information Nondiscrimination Act (GINA) prevents employers from using that information Read More
Whole Exome Sequencing: The Next Big Thing
May 18, 2011
It’s mid-May, when I hear from students who’ve used my human genetics textbook spring semester. Olivia Kegler, a senior at Cor Jesu Academy in St. Louis, e-mailed: “We’re wondering what you think the next major genetics project will be?”
The next e-mail, the table of contents for May’s American Journal of Human Genetics, answered Olivia’s question: whole exome sequencing.
The exome is the Cliff’s/Spark Notes version of the genome, the part that encodes the proteins that keep our bodies growing and going. It’s only about 2 percent of our 3.2 billion DNA bases, but it holds out hope for families with inherited diseases so rare that physicians are stymied, databases useless.
The May issue of AJHG has three interesting entries for exome sequencing: a combo of weak tooth enamel and overgrown gums (amelogenesis imperfecta and gingival hyperplasia syndrome), heart failure in babies (infantile mitochondrial cardiomyopathy), and a rapid-aging disease (hereditary progeroid syndrome).
For people with the same mysterious medical condition, whole exome sequencing looks for unusual DNA sequences that they share, often a single DNA base. If the implicated gene makes sense, the next step is to see if it's expressed – makes its protein – in the affected tissues. For the first case, the gene does its thing in the teeth and gums; for the second case, a mutation disrupts how chromosomes touch the inner surface of the nucleus, just like in the better-studied progeria that makes children look elderly; for the third case, the mutation shuts down mitochondrial energy factories in cardiac muscle, starving the hearts of babies. Whole exome sequencing makes sense, and can provide clues to treatments.
The media have begun to cover some of the first families to have whole exome sequencing. I’m following a family with two little girls who have visual loss and other symptoms. After spending thousands of dollars on tests that rounded up the usual suspects, with no answers, the parents sent the family’s DNA to a researcher who is sequencing their exomes.
Stay tuned … while celebrities have their genomes done and regular people have fun with DNA testing, for families with rare diseases, whole exome sequencing is finally bringing answers.
Thanks, Olivia! Read More
The next e-mail, the table of contents for May’s American Journal of Human Genetics, answered Olivia’s question: whole exome sequencing.
The exome is the Cliff’s/Spark Notes version of the genome, the part that encodes the proteins that keep our bodies growing and going. It’s only about 2 percent of our 3.2 billion DNA bases, but it holds out hope for families with inherited diseases so rare that physicians are stymied, databases useless.
The May issue of AJHG has three interesting entries for exome sequencing: a combo of weak tooth enamel and overgrown gums (amelogenesis imperfecta and gingival hyperplasia syndrome), heart failure in babies (infantile mitochondrial cardiomyopathy), and a rapid-aging disease (hereditary progeroid syndrome).
For people with the same mysterious medical condition, whole exome sequencing looks for unusual DNA sequences that they share, often a single DNA base. If the implicated gene makes sense, the next step is to see if it's expressed – makes its protein – in the affected tissues. For the first case, the gene does its thing in the teeth and gums; for the second case, a mutation disrupts how chromosomes touch the inner surface of the nucleus, just like in the better-studied progeria that makes children look elderly; for the third case, the mutation shuts down mitochondrial energy factories in cardiac muscle, starving the hearts of babies. Whole exome sequencing makes sense, and can provide clues to treatments.
The media have begun to cover some of the first families to have whole exome sequencing. I’m following a family with two little girls who have visual loss and other symptoms. After spending thousands of dollars on tests that rounded up the usual suspects, with no answers, the parents sent the family’s DNA to a researcher who is sequencing their exomes.
Stay tuned … while celebrities have their genomes done and regular people have fun with DNA testing, for families with rare diseases, whole exome sequencing is finally bringing answers.
Thanks, Olivia! Read More