12th edition of my human genetics textbook


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

Genetic Linkage

Y Chromosomes in the News and #MeToo

September 18, 2018

Tags: Y chromosome

The firing of CBS CEO Les Moonves for his alleged history of revolting attacks on women and the upcoming one-year anniversary of Ronan Farrow’s seminal New Yorker piece on Harvey Weinstein and of Alyssa Milano’s #MeToo tweet echoing Tarana Burke’s 2006 call-to-action, got me pondering the Y chromosome.

Genomically speaking, the diminutive Y is the only thing that distinguishes males from females (see “Y Envy"). Both sexes have X chromosomes, and although mitochondrial DNA passes from females to all offspring, we all have mitochondria. Only the Y is the male’s alone.

If size matters, the Y chromosome loses. The human X has about 1500 protein-encoding genes compared to the Y’s 231, some of which have counterparts on the X. Only a handful of Y genes, in the “male-specific region” of the chromosome, are uniquely male. They include the SRY gene that determines maleness and a few others that control fertility.

So the Y chromosome can tell us some interesting things about the male of the species.

To continue reading go to DNA Science, where this post first appeared.

Gene Silencing Through RNA Interference Scores First Drug Approval

September 11, 2018

Tags: RNA interference, RNAi

The Food and Drug Administration recently approved the first drug based on RNA interference (RNAi). Unlike media darlings gene therapy and gene editing, RNAi silences genes. The first approval is a milestone two decades in the making.

The new drug, Onpattro (patisiran), treats the tingling, tickling, and burning sensations from the rare condition hereditary transthyretin-mediated amyloidosis, aka hATTR. About 3,000 people have it in the US. Alnylam Pharmaceuticals provides this “first-of-its-kind RNA interference (RNAi) therapeutic.” Like other new nucleic-acid based treatments, it’s pricey. The cost per year for the every-third-week intravenous infusion is $450,000.

To continue reading go to Genetic Literacy Project, where this post first appeared.

Matching Cancer Patients to Targeted Drugs: Two New Tools

September 9, 2018

Tags: cancer, machine learning, Cerebro, Keytruda, Gleevec, Herceptin

A choreography of mutational events drives cancer cells to invade and metastasize, changing the biology in ways that enable the errant cells to resist treatments. While the traditional slash-and-burn approaches of chemotherapy and radiation attack rapidly-dividing cells, targeted treatments zero in on the altered proteins that reflect precise genetic changes in tumor cells. These are the somatic (“body”) mutations in just the affected cells, not the inherited mutations present in all of a patient’s cells.

Two new papers introduce tools to better match patients to targeted treatments or immunotherapies, based on interpreting the mutations behind a cancer’s initiation and spread. One is a machine learning tool called Cerebro, the other a scale for physicians to rank the evidence that a particular targeted treatment will work against a tumor with specific mutations.

To continue reading go to DNA Science Blog at Public Library of Science, where this post first appeared.

The Cave Where It Happened: The Daughter of a Neanderthal Mom and a Denisovan Dad

August 24, 2018

Tags: Denisovan, Neanderthal

Svante Pääbo and a friend.
Once upon a time, in a cave in the Altai Mountains of southern Siberia, different types of ancient peoples were having sex.

A new report in Nature from Svante Pääbo, the Max Planck Institute for Evolutionary Anthropology superstar, and his team introduces the young teen “Denisova 11.” I’ll call her Eleven, in honor of the beloved character in the TV show Stranger Things. She was a type of archaic human called a Denisovan, pronounced “Denise-o-van.”

The title of the new paper tells the whole tale: “The genome of the offspring of a Neandertal mother and a Denisovan father.”

Introducing Denise

The research team introduced the first Denisovan, named Denise, in 2010, based on a preliminary genome sequence from her finger bone, discovered in 2008 in the cave. Denise lived 32,000 to 50,000 years ago and had dark skin and brown eyes and hair. Her genome included some Neanderthal sequences, so it was clear there’d been some mixing of genomes going on.

To continue reading go to DNA Science blog, where this post first appeared.

Were There Two Routes into North America? Genetics Meets Archaeology

August 24, 2018

Tags: Beringia, land bridge

Popular accounts of the peopling of North America paint a picture of a lone long-ago trek across the Bering Land Bridge and then south along the Pacific coast, a view based largely on DNA evidence. But other clues point to people also traversing “ice-free corridors” that emerged from melting glaciers like terrestrial tentacles.

A new paper in Science Advances reviews the evidence for more than one way into North America. It concludes that people followed at least two routes, coastal and interior, and that the view over the land bridge “commonly disseminated in the popular press is a prematurely narrow interpretation of current evidence.” The journal held a news conference with three of the investigators.

"We’ve seen conflicting narratives about the timing and the nature of the peopling of the Americas. We wanted to evaluate this claim and provide a framework to discuss the process – not based on speculation but on a critical review of current evidence. Rather than confusion, there is growing congruence of the archeological, paleoecological, and genetic records," said co-author and archaeologist Ben Potter, professor of anthropology at the University of Alaska, Fairbanks.

More philosophically, the report beautifully illustrates scientific inquiry, operating in a blind-man-and-the-elephant sort of way, revealing not alternate facts, but multiple solutions to a shared challenge – a search for habitable land. It also touches on ways to avoid so-called in
"helicopter research,"
in which wealthy nations send expeditions to probe the health and lives of poorer people, without involving them in the work.

To continue reading go to Genetic Literacy Project, where this post first appeared.

New Book, “Run to the Light,” Chronicles a Journey with Batten Disease

August 24, 2018

Tags: Batten disease, Run to the Light, Laura King Edwards, CLN1

On November 1, Laura King Edwards’s inspiring book “Run To The Light” will be published, by Bedazzled Ink.

The memoir is an astonishing tale of a sister’s love and how she is coping with a tragic and inevitable future for her younger sibling. It’s also the tale of how one family’s activism has led to a gene therapy in development to treat Taylor’s inherited neurological condition.

The book is also about running – blindfolded.

“Run to the Light” sets up the story in just the second sentence: “We found out my little sister was dying on a parched morning in the summer of 2006, just a few weeks shy of her eighth birthday and a month after my wedding.”

To continue reading go to DNA Science Blog, where this post first appeared.


Is CRISPR Gene Editing Doomed, Even As Gene Therapy Enters the Clinic?

August 15, 2018

Tags: CRISPR, gene therapy

Anyone watching the recent 60 Minutes segment on CRISPR would conclude that the gene editing technology is on the brink of pouring forth a cascade of cures. But a recent study reveals a mess of missing and moved chromosome parts in the wake of deploying the famed “molecular scissors.”

Invented in 2012, CRISPR brilliantly borrows a bacterial defense against infection. The “clustered regularly interspaced short palindromic repeats” are simple DNA sequences that serve as landing strips in a genome where engineered “guide RNAs” deliver an enzyme to a desired gene, amending or obliterating it. When the enzyme snips across the double helix, natural DNA repair ensues. Cas9 is an oft-used enzyme.

Precision

Unlike conventional gene therapy that adds a gene, sometimes hovering in a DNA loop outside a chromosome, CRISPR swaps in or removes a gene at a precise spot. But it took 27 years for the FDA to approve the first gene therapy, Luxturna, to treat a specific form of hereditary blindness, last December. So CRISPRed drugs won’t be hitting CVS or Walgreen’s shelves anytime soon.

The new report, in Nature Biotechnology, from researchers at the Wellcome Sanger Institute, isn’t the first to find a CRISPR glitch, and it certainly won’t be the last.

To continue reading go to DNA Science Blog, where this post first appeared.


DNA Testing to Reunite Separated Families—What We Learned from the Grandmothers of Argentina

August 15, 2018

Tags: immigration, separated families, Grandmothers of the Plaza de Mayos

The idea to use DNA testing to reunite families separated at US borders due to the Trump administration’s “zero tolerance” policy arose quickly. But confusion ensued when early media reports didn’t distinguish the types of tests, which have different implications for privacy.

On June 21, in response to the heart-wrenching separation stories pervading the media, California Representative Jackie Speier first floated the idea of direct-to-consumer (DTC) genetic testing companies like 23andMe donating kits. Nice idea or outrageous, depending on one’s viewpoint.

Either way, the heavily-advertised 23andMe testing kits aren’t valuable for reuniting families, because they don’t catalog the statistically powerful short tandem repeats (STRs) that the FBI and immigration authorities rely on to identify individuals. Desperate, distraught parents and crying, terrified kids — or children traumatized into eerie silence — aren’t going to find each other from cheek swabs at the border revealing visible traits, disease risks, earwax consistency, or whether cilantro tastes foul or yummy.

But testing DNA to reunite relatives has worked before, although under wildly different circumstances. A precedent is the Grandmothers of the Plaza de Mayos project. It began in 1977, a year into the eight-year “Dirty War” when the Argentinean military and police abducted at least 210 “niños desaparecidos,” selling them or giving them away. The Grandmothers project built cases using conventional evidence, such as documents, to attempt to reunite kidnapped children with relatives. Why grandmothers? Because so many mothers had been murdered.

But the evidence wasn’t enough.

So in 1984, the American Association for the Advancement of Science sent a team of geneticists to Buenos Aires to assist the Grandmother project, including Mary-Claire King, not yet famous for discovering the BRCA breast cancer genes.

To continue reading go to Genetic Literacy Project, where this post first appeared.

How the Media Oversimplifies DNA Testing of Separated Families

August 7, 2018

Tags: DNA testing, STR, CODIS, immigrant DNA testing

Should DNA testing be used to help reunite separated immigrant families?
When the Genetic Information Nondiscrimination Act of 2008 (GINA) was passed to unify “the existing patchwork of State and Federal laws,” the language was broad enough to apply to just about any use of information gleaned from DNA. The law is meant to prevent discrimination in health insurance and employment based on results of a “genetic test,” defined as “an analysis of human DNA, RNA, chromosomes, proteins, or metabolites, that detects genotypes, mutations, or chromosomal changes.”

Use of “genotypes” alone covers any application of determining sequences of A, T, C, and G that I can think of, and if that’s not enough, the first sentence of the act mentions sequencing the human genome.

A decade ago also came the first direct-to-consumer (DTC) DNA tests, from a handful of companies. Since then the number and types of “spit” and cheek swab tests and companies offering them have mushroomed, probing traits, tendencies, risks of future illness, metabolic quirks, behavioral characteristics, carrier status for single-gene diseases, and of course ancestry. But with the spreading tentacles of DNA testing, a lack of precision in describing what, exactly, is being considered, can lead to misunderstanding. That’s apparent in the use of DNA testing to help to reunite children separated from their parents as part of the Trump administration’s “zero tolerance” policy at U.S. borders.

Don’t Echo Politicians Who Gloss Over the Science

Initial confusion about DNA testing unfurled June 21 when California Representative Jackie Speier called for DTC DNA testing company 23andMe to donate kits for swabbing children’s cheeks at the borders.

Continue reading at DNA Science, where this post first appeared.

Identical Twins, Physical Fitness, and Transgender Identity in the News

July 27, 2018

Tags: Three Identical Strangers, twins, transgender

The terrific new documentary "Three Identical Strangers" tells the remarkable tale of triplets separated in infancy who met for the first time at age 19, in 1980. Their matching faces, mannerisms, behaviors, and quirks reverberate throughout the film, astonishing because the triplets were raised in economically diverse families. The film pays less attention to what makes them different.

Identical Twins That Differ Markedly in Physical Fitness

Another intriguing case of nature vs nurture in identicals is published in the new issue of The European Journal of Applied Physiology. Katherine Bathgate, James R. Bagley, and Andrew J. Galpin and their colleagues, from a trio of California colleges, compared 52-year-old identical twins who differ greatly in their physical fitness level. “TT” is a runner and triathlete, “UT” a sedentary truck driver. Because they share all their genes, differences in physical fitness reflect what the twins do and have done, not what they inherited.

To continue reading go to DNA Science, where this post first appeared.

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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