Tag Archives: genetics

NIH scientists identify a genetic disorder that may affect 1 in 20

[Mast cells from a sinus stained in blue. Image via Wikimedia Commons & CC 2.0] 

On July 10, 2010, a DC restauranteur came down with what seemed to be food poisoning. He had no energy and no appetite. Rashes flared up. He could barely get out of bed. First hours and then days dragged by without any relief from the symptoms.

The restauranteur’s family sought out doctor after doctor, until finally they were referred to a lab at the NIH (National Institutes of Health) that studies how allergies pass down through families. 

His symptoms fit a diagnosis of Mast Cell Activation Syndrome, (MCAS)  a disorder where a type of immune cells called mast cells release chemicals that send other immune cells into a destructive frenzy. Ideally, mast cells detect infection and spur other immune cells into action. However, some people’s mast cells have a hair trigger. When mast cells release their chemical contents too often, immune cells end up attacking healthy tissue, causing allergies, stomach issues, and heart palpitations. 

[Above: An NIH-produced video about MCAS and Milner’s research into mast cell activation genetics.] 

Unfortunately, most treatments for MCAS aim at the symptoms, not the root cause.  But the NIH team delved deeper into the genetics and found a pattern:  many MCAS-related symptoms run in families.

And oddly enough, hyperflexible joints, dysautonomia, and baby teeth that fail to fall out also ran in many of those families. Many of these symptoms skipped generations, only showing up occasionally in individuals. But genetic sequencing revealed the correlation wasn’t coincidence.

In October, NIH scientist Joshua Milner and his team described the  genetic disorder in a paper in Nature Genetics. According to the team’s paper, 4-6% of the U.S. population has the genes that predispose them to this syndrome–which has been tentatively named alpha-tryptasemia or “alpha-T”.

The symptoms can be cryptic and unrelenting: Dizziness, chronic pain, irritable bowels, fainting. But for many patients with these conditions, there’s no explanation and no treatment. “These [symptoms] are really all triggers to get an eyeroll from a doctor,” said Milner. But for a sizeable portion of population, these seemingly unrelated problems might be part of the previously undiscovered genetic disorder.

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Hybrid Problems: Chimerism, Synthetic Life, and Mixed Heritage

[A hybrid orchid. Photo by Mark Freeth.] 

[“Molecularization of Identity” Workshop Recap, Part 2]

Genomes of indigenous people, which often include genes found nowhere else in the world, can be powerful symbols for nations that want to showcase their uniqueness. 

But when the Mexico’s Instituto Nacional de Medicina Genómica  (INMEGEN)  set out to find examples of Mexico’s indigenous genome, they ran into problems. Namely, that pretty much every population in Mexico, no matter how remote, includes people of mixed ethnic ancestry.

INMEGEN’s attempts to reconstruct an indigenous identity were the focus of not one, but two talks at Harvard STS’s “Molecularization of Identity Conference“, one by Vivette García Deister–who teaches in the Science & Technology Studies department at Universidad Nacional Autónoma de México– and one by Ernesto Schwartz Marin of Durham University.  Since that conference was chock-full of important studies on the social dynamics around science, I’m writing a 3-part recap, of which this post is part 2. (See Part 1 here).

García Deister began her presentation by introducing the concept of Mestizaje, a blend of Native American, Spanish/European, and African heritage that characterizes Latin American countries. The majority of Mexicans are of Mestizo–or “mixed” descent–so naturally, the Mexican government wanted to know the ratios of  “Amerindian”, “European”, and “African” genes in their country’s population.

To do that, they had to try to establish a baseline “Indigenous” genome to compare to their representative “Mestizo” genome. García Deister calls these hypothetical representative genomes “Genetic Avatars”. 

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[Interestingly, the “avatars” in the uber-successful movie Avatar are literally synthetic genetic hybrids, with human DNA spliced into Na’vi genome. Image by Michael Kordahl.]

Colonist outsiders love to look for “Genetic Avatars” because it gives them a way to quantify and tell stories about Latin American hybridity, or MestizajeGarcía Deister argued.  Scientists and policy makers  justify it by arguing that it’s important to know their country’s history and vital to look for genetic clues to various diseases.

But does any of that make the Mexican Genome Project any less of a colonial enterprise? Not really…

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“Perceive. Identify. Regulate.” How to be Racist with 21st Century Science

[Image via Brockhaus and Efron Encyclopedic Dictionary & Creative Commons]

[“Molecularization of Identity” Workshop Recap, Part 1]

The diagram of racism was shockingly simple: four highlighted brain regions with black arrows between them, forming an almost-isosceles triangle.

racism_brain_diagram

[Diagram by Elizabeth Phelps’ group at NYU via The Brain Bank blog]

Perception. Identification. Regulation. 

Those are the three steps in the cognition of racism, according to a handful of neuroscientists.

The diagram’s presenters weren’t the neuroscientists themselves, but a pair of sociologists who study neuroscientistsOliver Rollins of Penn and Torsten Heinemann of University of Hamburg.  The neuroscientists who try to spot neural patterns of racism in fMRI argue that  before a racist action occurs, several things happen in a person’s brain: First, they have to see or hear the other person, which triggers a response in the amygdala, a brain structure that contributes to people becoming jumpy and/or aggressive. Next, the signal moves to the anterior cingulate cortex, which identifies the other person as a threat or a non-threat. Finally, the signal moves to the prefrontal cortex, which makes a conscious decision: “Do I hurt or try to escape from this person?” 

The neuroscientists who study racism tend to be optimistic about the possibility of changing racist individuals’ cognition patterns via social interaction or even through medication, Rollins and Heinemann explained. However,  though the neuroscientists’ approach is commendable, it doesn’t address systemic racism. 

“If there’s a racist ‘Stop-and-Frisk‘ policy in place that allows you to stop any black men, it may not matter whether the individual cop has a racial bias,” Rollins said.

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5 Amazing Feats Performed by “Meta-Genes”

[Image via the NIH Image Gallery. Photo by Alex Ritter, Jennifer Lippincott Schwartz, and Gillian Griffiths. Full video, complete with narration here.] 

Under the Radar: A series of listicles about biology concepts you definitely won’t find in newspaper headlines.

#1: Be a Navigation App for Immune Cells

Natural killer cells, or “NK cells” are the human body’s best defense against cancer.  While other types of immune cells often ignore tumor cells, natural killer cells specialize in finding and destroying human cells that look either infected or like cancer mutants. In leukemia patients,  a higher number of active natural killer cells ups the patient’s chances for survival, so much so that  researchers are experimenting with transfusing NK cells into patients.

Just one problem there: Active natural killer cells die without a strong support network.

Dormant NK cells can survive in the bloodstream for a long time, but once activated, natural killers have to make a b-line for cells carrying a marker called IL-15 or die,  but until a study in Monday’s edtion of PNAS , no one knew how natural killers knew to look for IL-15. The study, led by Vanderbilt immunologist Eric Sebzda and grad student Whitney Rabacal, traced NK cells’ IL-15 homing ability back to a biochemical with the horrendous name “Kruppel-like Factor 2” (KLF2).

KLF2, oddly enough, also exerts a strong navigational influence on the immune system’s T-cells and B-cells.  Even though all three types of cells fall under the “white blood cell” umbrella, the notion that one protein could control navigation in all three is pretty weird.  Crawling and navigating are complex tasks, requiring coordination between dozens of genes. “[NK cell migration] is totally different from how t-cells and b-cells circulate,” Sebzda said.

Additionally, taking away KLF2 has distinctive effects on each type of cell: KLF2-less t-cells vacate the central body and crawl out to lab mice’s fingers and toes, KLF2-less b-cells all congregate at the spleen (which creates some serious problems for those lab mice), and KLF2-less natural killers end up dying alone.

So KLF2 could be super-useful for improving cancer immunotherapy. But why is KLF2 so versatile in the first place?

The answer lies in KLF2’s ability to bind to a certain recurring DNA base pair sequence, one that presumably earmarks the genes needed in each immune system navigation system, and it’s far from the only protein with such abilities…

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Splice of Life: 3 Examples of How Nature Edits Its Own Genes

About the “Under the Radar” series: Some scientific concepts come up again and again in interviews with scientists but never find their way into newspaper headlines. Each post in this series follows one of those biology “bogeys” that fly under journalism’s radar through 3 different mini-stories.

Story #1: Scientists splice up a CRISPR chicken…and find an evolutionary shortcut

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Birds’ brains have all of the tools to make mammal-like neurons, according to a study in Science from August And, incredibly, the researchers behind the study only had to tinker with one gene  that changes how chicken cells edit their RNA to unlock several seemingly unrelated mammal neuron traits in chicken neural precursor cells.

It was as if the chicken cells instantly acquired a whole bunch of mutations at once, instead of just one. 

Researchers think that this gene editing process– aka “alternative splicing”–may explain why some traits seem to have evolved at such high speeds.

“This is a process that has diverged very rapidly during evolution to produce different versions of proteins,” University of Toronto geneticist Ben Blencowe explained in a phone interview.

500 million years is a long time to evolve, but it’s still hard to account for all of the diversity in vertebrates based on variation in DNA base pairs alone.

The key to animal diversity lies in an aspect of biology that your high school biology class kinda sorta covered, but lots of people forget all the steps after they’re done cramming for the test.

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