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

Genetic Linkage

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…)

Genetic Sense and Nonsense

June 20, 2011

Tags: RNA modification, nonsense mutation, Cystic Fibrosis Foundation, World Federation of Hemophilia, Muscular Dystrophy Association, International Rett Syndrome Foundation, misfolded protein, Ricki Lewis, University of Rochester, targeted pseudouridylation, hemophilia, cystic fibrosis, Duchenne muscular dystrophy, Rett syndrome, genetic code, nonsense read-through, gentamicin, aminoglycoside antibiotics, progressive supranuclear palsy, PSP, Perelman School of Medicine, University of Pennsylvania, Nature, Gerard Schellenberg, Yi-Tao Yu

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!

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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