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

Genetic Linkage

Defying Mendelian Genetics and "Embryo Engineering"

February 19, 2017

Tags: embryo engineering, de novo mutation, uniparental disomy Bainbridge-Ropers syndrome, giant axonal neuropathy

(credit: Children's Mercy Kansas City)
Mendel’s laws, like any laws in science, make predictions possible. A woman and man both carry a recessive mutation in the same gene, and each of their children has a 25% chance of inheriting both mutations and the associated health condition.

In contrast to our bizarre new world of “alternate facts,” science is both logical and rational. If an observation seems to counter dogma, then we investigate and get to the truth. That’s what happened for Millie and Hannah, whose stories illustrate two ways that genetic disease can seem to veer from the predictions of Mendel’s first law: that genes segregate, one copy from each parent into sperm and ova, and reunite at fertilization. (I’ll get to embryo engineering at the end.)

Millie’s situation is increasingly common – exome or genome sequencing of a child-parent “trio” reveals a new (“de novo”), dominant mutation in the child, causing a disease that is genetic but not inherited.

Hannah’s situation is much rarer: inheriting a double dose of a mutation from one parent and no copies of the gene from the other. (more…)

Pig People?

February 4, 2017

Tags: pig/human chimera

When Medscape asked me late last week to cover the making of early embryos that have cells from pigs and humans, I couldn’t help but flash back to the Pigman episode of Seinfeld. "The government's been experimenting with pig-men since the '50s!" warned a terrified Kramer after finding one such creature hidden on the top floor of a hospital.

We didn't see Kramer’s porcine/human chimera of the 1990s, but a 1960 episode of the Twilight Zone, The Eye of the Beholder, provides an earlier illustration of the mixing of the species. (more…)

12 Alternative Facts of Human Genetics

January 28, 2017

Tags: alternative facts, Kellyanne Conway, history of genetics, Mendel, Griffith

I’ve always wanted to write about my favorite experiment in human genetics, but a news hook was elusive. Not any more! Thank you Kellyanne Conway for your intriguing concept of "alternative facts."

I’m writing the 12th edition of my human genetics textbook right now, so it’s the perfect time to browse through the pages and select a few turning points in time when genetic reality might have diverged, leading to different outcomes, if "alternative facts" were possible. But first, to illustrate how scientists reject hypotheses to reach a conclusion, a brief review of what’s been called "The Most Beautiful Experiment in Biology". (more…)

A Necessary Retelling of the Smallpox Vaccine Story

January 17, 2017

Tags: vaccine, smallpox, Edward Jenner, Donald Trump, RFK Jr, autism, anti-vaxxer

People once feared that small cows would emerge from the arms of vaccinated people. Ignorance about vaccines persists.
A curious confluence of events unfolded January 10. Just hours before President Obama uttered the powerful “science and reason matter” in his farewell address, Robert F. Kennedy Jr. announced that the incoming president had tapped him to head a committee on vaccine safety.

RFK Jr. is not a pediatric immunologist nor an epidemiologist, but a vocal "vaccine skeptic". Although the PEOTUS dialed back on the purported appointment shortly after social media erupted, a tweet from March 28, 2014 clarifies the new president’s analysis of the history and science of vaccines:

Healthy young child goes to doctor, gets pumped with massive shot of many vaccines, doesn’t feel good and changes – AUTISM. Many such cases! (more…)

Gene Action Tracks an Autoimmune Disease: Systemic Sclerosis

January 5, 2017

Tags: systemic sclerosis, scleroderma

Systemic sclerosis (Ssc) is a rare disease in which collagen gloms up internal organs and toughens the skin into an armor of sorts. It's also called scleroderma, from the Greek for “hard” (skleros) and “skin” (derma). Ssc is autoimmune, not inherited, but a recent report in JCI Insight describes how gene expression profiling -- transcriptomics – can add precision to diagnosis, monitor response to treatment, and identify drugs that might be repurposed to target SSc. (more…)

Genetics Error in "The Man in the High Castle" Season 2?

January 4, 2017

Tags: The Man in the High Castle

What if the Germans and Japanese had won WW2?
I’ve just finished watching season 2 of Amazon video’s terrifying The Man in the High Castle, which depicts an alternate reality in which Germany and Japan won the second world war, with an atomic bomb taking out Washington, DC. I admit confusion over gaping plot holes and teasers, but I did catch enough of the dialog to suspect that genetic info about one of the families is wrong.

Thomas Smith, adolescent son of Obergruppenführer John Smith, has a form of muscular dystrophy. According to a footnote in Wikipedia, it is Landouzy-Dejerine syndrome, which I hadn’t heard of by that name but recognized its name today, facioscapulohumeral muscular dystrophy (FSHD). It is autosomal dominant – if you have it, so does or did one of your parents, unless you're a new mutation (about 30 percent of cases).

In a 10-second scene in the final episode, we learn that John Smith’s uncle had the disease, and that his two daughters must be carriers.

Well, no.

A dominant condition doesn’t have carriers. You have the mutation or you don't, although symptoms may occur later in life, in which case a person with the mutation is pre-manifest, not a carrier in the classic sense. Since Tom’s uncle had it too, presumably before the State murdered him, and the condition is rare, it must be inherited, not due to a new mutation. I can only reconcile these facts if John Smith has the mutation too but is non-penetrant – meaning he has the genotype but not the phenotype. I wonder what the Nazis, obsessed with purifying the gene pool, would do with that intel! Plus, Thomas has what appears to be seizures and he trips – not the upper body weakness of the disease.

I suppose the writers chose FSHD because it isn’t horrible, making it more horrible that the Nazis exterminate those who have it. When Thomas realizes that he’s not healthy, he mutters the mantras “I’m a useless eater” and “I'm defective.”

I won’t spoil the ending. But can anyone explain an inheritance pattern that has carriers and non-penetrance? Meanwhile, maybe the new showrunner for season 3 will take a genetics course.

Genetics in 2016: Breakthrough, Breakdown, and Bridge

December 21, 2016

Tags: gene therapy, CAR-T technology, exon skipping, Duchenne muscular dystrophy, spinal muscular atrophy, DMD, SMA

I dislike end-of-year "best of" lists, especially the "breakthroughs" that imply scientific discoveries and medical advances emerge from out of nowhere. Often they're the product of PR machines that select and then catapult certain research findings into the news releases that dictate the headlines.

WHAT MAKES SCIENCE NEWS?
Much of science news is released to journalists ahead of time (embargoed) so that we can investigate background and conduct interviews. This year, the Food and Drug Administration began offering news even earlier to select media outlets. (more…)

Linking Gaucher and Parkinson’s Diseases

December 11, 2016

Tags: Gaucher disease, Parkinson's disease, lysosomal storage disease

"Gaucher cells" have a crinkly appearance from the build-up of glucocerebroside.
This month, JScreen’s ”Spit Happens" campaign is covering all costs not met by insurance for testing for carrier status for Gaucher disease, thanks to funding from the National Gaucher Foundation. The "spit happens" is an entertaining view of people spitting into tubes to collect DNA from dislodged cheek lining cells. (more…)

Parent Roundtable: Before and After Gene Therapy

December 2, 2016

Tags: gene therapy, rare diseases

Eliza had gene therapy this past spring, and is showing small signs of improvement.
As the revamped 21st Century Cures Act winds its way through the lame duck Congress, I’m reminded of a spellbinding dinner on Sunday night, October 16. It was the eve of the annual "breakthrough summit" for the National Organization for Rare Disorders, and I’d introduced a group of new friends to share their stories of life with a child who has had, or will have, gene therapy. (more…)

Why I Yanked "Morlock Nation"

November 13, 2016

Tags: Donald Trump and the New Morlock Nation

On Thursday, November 10, I briefly posted a blog called “Donald Trump and the New Morlock Nation” on my usual website (not this one). I took the post down after threatening comments were posted and the tone was escalating.

I regret having given up my first amendment rights to bullies. I would rather have had a conversation. The commenters did not understand my point – that our differences taken to extremes and under some pretty unlikely circumstances (plus a very long time) could theoretically lead to a speciation event.

The post dealt with the contribution of heredity to intelligence. I used many disclaimers and never used a judgmental term such as “subspecies,” although I was accused of having done so.

My scenario based on theoretical population genetics had appropriate links to back up my hypothesis – for that is all it was. I meant no harm.

If anyone wishes to contact me through this website, I can send a word document by email, with or without links, of the post. This offer is to promote education.

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 10th edition.
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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