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Genetic Linkage

What’s In A (Disease) Name?

Vincent Pieterse has some unusual traits, and a rare mutation. Are they related as a novel syndrome -- or not?
Marc Pieterse was angry.

His son Vincent’s unusual features – long, thick eyelashes; low-set ears; extra teeth; autistic behaviors; brittle hair; flat back of the head; hearing loss; developmental delay – had led Marc, an engineer and self-taught geneticist, to seek exome sequencing. He knew that strange combinations of traits could mean a mutation.

Sequencing Vincent’s exome – the protein-encoding part of the genome – could reveal if a new mutation had arisen in him, rather than having been inherited from his parents. And that’s what happened. Vincent has his own dominant mutation in a gene called RPS23. He isn’t, however, defined by any disease. He’s a striking, active, and happy young teen who loves watching and listening to birds as he rides his mountain bike to school through a nature reserve. Read More 
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Can CRISPR Conquer Huntington’s?

In HD extended huntingtin protein builds up in medium spiny neurons in the striatum.
I set a high bar for writing about mouse studies. I don’t include them in my textbooks or news articles, and only rarely blog about them. But when experiments in mice shine a glimmer of hope on a horrific illness with a long history of failed treatments, I pay attention. That happened last week for a report on editing out of mice the human version of the mutant Htt gene that causes Huntington disease (HD), published in the Journal of Clinical InvestigationRead More 
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Can We Cure Huntington’s Disease?

I didn’t cry until page 123 of Lisa Genova’s terrific new novel "Inside the O'Briens". That’s when 44-year-old Boston police officer Joe O’Brien calmly explains to his four young adult offspring that his “weird temper”; his frequent toe-tapping, shoulder-shifting, and eyebrow lifting; and his inability to sequence the events in a routine crime report, are all due to Huntington’s disease (HD).

As a boy, Joe believed the neighborhood talk that his institutionalized mother was an alcoholic. He remembers his skeletal, writhing, grimacing and grunting mother as a monster, not as someone suffering from a neurological disease only trying to say “I love you” to her terrified son. Read More 
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Juvenile Huntington's Disease: The Cruel Mutation

Jane and Karli Mervar
Looking back, signs that Jane Mervar’s husband, Karl, had Huntington’s Disease (HD) started about when their youngest daughter, Karli, began to have trouble paying attention in school. Karl had become abusive, paranoid, and unemployable due to his drunken appearance. The little girl, born in September 1996, was hyperactive and had difficulty following directions. When by age 5 Karli’s left side occasionally stiffened and her movements slowed, Jane began the diagnostic journey that would end with Karli’s diagnosis of HD, which had affected the little girl’s paternal grandmother.

Soon Karli could no longer skip, hop, or jump. And new troubles emerged. Read More 
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Anticipation

Jordan and Hailey Kohl. Spinocerebellar ataxia type 2 affects several members of their family, including Jordan.
“Anticipation .. is keepin’ me waitin’,” sings Carly Simon in her song made famous in a ketchup commercial. But “anticipation” in the genetic sense is just the opposite of Carly’s croon – it means a disease that begins earlier with each generation.

Doctors once blamed patients for anticipation, as if people with sick older relatives could worry themselves into suffering similarly. Then, in 1991, discovery of a new type of mutation explained the curious worsening of fragile X syndrome: an expanding triplet repeat.  Read More 
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Personal Genome Sequencing: Too Much Information?

October 11-15, 6,200 researchers and clinicians met in Montreal for the 12th International Congress of Human Genetics. After my brain recovered from the long days of meetings, one panel discussion emerged as my favorite: what I thought was going to be a dull comparison of DNA sequencing technologies turned out to be a spirited look at  Read More 
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23andMe's Exome Sequencing and the Tenth Edition of My Textbook

It’s been a strange week. The tenth edition of my human genetics textbook was published, just as 23andMe announced that they now offer whole exome sequencing, for $999. Read More 
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Fruit Flies Bring Good News to Huntington's Disease Families

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 
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