genetics and genomics

Scientists Uncover Common Cell Signaling Pathway Awry in Some Types of Autism

Brain cells grow faster in children with some forms of autism due to distinct changes in core cell signaling patterns, according to research from the laboratory of Anthony Wynshaw-Boris, MD, PhD, chair of the department of genetics and genome sciences at Case Western Reserve University School of Medicine, and a member of the Case Comprehensive Cancer Center. Rapid cell growth can cause early brain overgrowth, a common feature in 20-30% of autistic children. But, the genetics of autistic children vary making it difficult to pinpoint common mechanisms underlying the disease.

“Autism is a complex disorder with multiple genetic and non-genetic factors,” explained Wynshaw-Boris. “Because the causes are diverse, it may help to define a subset of patients that have a common [symptom], in this case early brain overgrowth.”

In a study published in Molecular Psychiatry, Wynshaw-Boris and his colleagues started with skin cell samples from autistic children with enlarged brains and worked backward. Researchers in the laboratory “reprogrammed” donated skin cells to produce cells found in the developing brain including induced pluripotent stem cells and neural progenitor cells. Stem and progenitor cells are important therapeutic tools as they have the potential to grow into a multitude of cell types. The researchers hypothesized that even though the children in the study had different forms of autism, the precursor cells could be used to find common molecular and cellular mechanisms.

The researchers discovered that cells derived from autistic donors grew faster than those from control subjects and activated their genes in distinct patterns. Genes related to cell growth were unusually active, leading to more cells but fewer connections between them. This can cause faulty cell networks unable to properly transmit signals in the brain and enlarged heads during early development.

The researchers identified abnormal genes in the cells grown from autistic donors as belonging to the Wnt signaling pathway. The Wnt genes are critical for cell growth and serve as central players in cell networks, interfacing with multiple signaling pathways. Wynshaw-Boris previously identified the Wnt pathway as related to autism in mouse models of the disease. In a separate study published in Molecular Psychiatry earlier this year, the Wynshaw-Boris laboratory showed mice lacking Wnt genes display autism-like symptoms including social anxiety and repetitive behavior. The researchers could prevent these adult symptoms by treating the mice with medications that activate Wnt signaling in the uterus, during development.

“The Wnt pathway is one of the core developmental pathways conserved from invertebrates to humans. Our studies solidify previous suggestions that this pathway has a role in autism,” said Wynshaw-Boris.

Once they identified the dysfunctional signaling pathway in their reprogrammed autistic samples, the researchers (including the laboratories of Alysson Muotri, PhD at the University of California San Diego and Fred Gage, PhD at the Salk Institute) attempted to correct it by exposing mature nerve cells derived from autistic donors to drug compounds. One drug currently being tested in clinical trials for autism is insulin growth factor 1 (IGF-1). When the researchers added IGF-1 to nerve cells derived from autistic donors, neural networks were reestablished. It is unclear whether the positive effects of IGF-1 were on the Wnt pathway, and the exact compensatory mechanism requires further investigation.

Wynshaw-Boris’s studies in cell culture and mouse models of autism confirm improper Wnt signaling can lead to rapid brain cell growth and brain enlargement in the embryo, resulting in abnormal social behavior after birth. The next step will be to determine which genes are most impacted by Wnt signaling defects during early development, and how these changes result in abnormal behavior. “We would also like to find other drugs or compounds that may slow down the growth of the cells in tissue culture,” said Wynshaw-Boris. Together, these findings may help researchers unravel common ways brain cells can become impaired during early development in carefully chosen subsets of patients and contribute to symptoms across the autism spectrum.

The health of our global citizenry is not a partisan subject. Frankly, it doesn’t matter what Repubs or Dems want, or even what you or I ‘think’ we want; rather, it’s about what we need, based on empirical, evidence-based decision making by which the data reveal to be the most accurate path to sustainability.

Led by the men and women on the forefront of medical research across an array of fields: biology, meteorology, genetics, genomics, artificial intelligence, machine learning, physiology, neuroscience, psychology, climatology, oceanography, ecology, biodiversity, agriculture, planetary science, geophysics, anthropology, paleontology, economics…the list of related concentrations pertaining to the health and survival of life necessary amongst the diverse family thriving in this biosphere are contributing to the information needed to address tomorrow.

Yet, Carl Sagan’s words still, hauntingly, ring true for our society in its present condition:

“We live in a society exquisitely dependent on science and technology, in which hardly anyone knows anything about science and technology.”

He followed by rhetorically postulating, “Who is making the decisions about science and technology in a democracy where no one understands anything about science and technology?”

Make no mistake – understanding how the world works at the fundamental level is not only liberating and exciting, it’s crucial in order to safeguard one’s intellect from being able to determine fact from fiction. And when arguments from authority are presented or asserted in a reactionary way, a continuously refined skepticism and knowledge of science (pertaining to and incorporating a global view of our society) will prevent us from being lied to so that we may hold said authority accountable. With persistence, we will appoint authority figures to positions of influence whom are scientifically literate themselves; that is, if artificial intelligence doesn’t step in and fill these roles for us to correct for human error.

To this end, I find it disturbing that the health and sustainability of our society has become so politicized and polarized to ad nauseam, moving beyond simple hypocrisy. Complaining about our imperfect healthcare system while pushing for environmental deregulation and, simultaneously, a resurgence of fossil fuels, is not hypocritical; it’s ignorance. Madness. And it’s betraying the very biosphere which enabled our existence, and enables it still.

—  @sagansense

So uh

Last night I 

Kind of got a little drunk

And made this

Octopus genome holds clues to uncanny intelligence
DNA sequence expanded in areas otherwise reserved for vertebrates.

With its eight prehensile arms lined with suckers, camera-like eyes, elaborate repertoire of camouflage tricks and spooky intelligence, the octopus is like no other creature on Earth.

Added to those distinctions is an unusually large genome, described in Nature1 on 12 August, that helps to explain how a mere mollusc evolved into an otherworldly being.

“It’s the first sequenced genome from something like an alien,” jokes neurobiologist Clifton Ragsdale of the University of Chicago in Illinois, who co-led the genetic analysis of the California two-spot octopus (Octopus bimaculoides).

The work was carried out by researchers from the University of Chicago, the University of California, Berkeley, the University of Heidelberg in Germany and the Okinawa Institute of Science and Technology in Japan. The scientists also investigated gene expression in twelve different types of octopus tissue.

“It’s important for us to know the genome, because it gives us insights into how the sophisticated cognitive skills of octopuses evolved,” says neurobiologist Benny Hochner at the Hebrew University of Jerusalem in Israel, who has studied octopus neurophysiology for 20 years. Researchers want to understand how the cephalopods, a class of free-floating molluscs, produced a creature that is clever enough to navigate highly complex mazes and open jars filled with tasty crabs.

Continue Reading.

Henrietta Lacks was the only human being to carry genetics ( The Hela Genome) resistant to all known human diseases. During a cervical exam, doctors took her cells and continued to take her cells through future exams in order to create vaccines that created resistance to measles, mumps, polio, HIV, and all other known viruses. All of this was done without her knowledge, consent and compensation. Her story is finally getting told. Happy Black History Month.
Gene-edited 'micropigs' to be sold as pets at Chinese institute
Cutting-edge gene-editing techniques have produced an unexpected byproduct — tiny pigs that a leading Chinese genomics institute will soon sell as pets. The pigs are endearing but scientists warn that they may be a distraction from more serious research.

“I’m fascinated by the idea that genetics is digital. A gene is a long sequence of coded letters, like computer information. Modern biology is becoming very much a branch of information technology.”
 ― Richard Dawkins

Scientists just successfully edited a human embryo’s genes.

In a plot line straight out of a futuristic sci-fi movie, a group of scientists in China have modified the genome of a human embryo for the first time. Their research could lead to major developments in science and medicine, such as wiping out genetic diseases and even restoring lost species of life. But there are major concerns.


Octopus genome: Suckers and smarts  

Researchers from the University of Chicago have sequenced the octopus genome, and they were surprised by what they saw; watch this Nature video to find out why


Octopus genome: Suckers and smarts

Researchers from the University of Chicago have sequenced the octopus genome, and they were surprised by what they saw; watch this Nature video to find out why.

Read the paper: The octopus genome and the evolution of cephalopod neural and morphological novelties.

By: nature video.
2015 was the year it became OK to genetically engineer babies - Quartz

When the first atom bomb detonated the humanity was changed forever. For the first time the human race was weilding a power that had the potential to exterminate humankind. And the arena of global politics dramatically changed soon after that.

Today we don’t even raise our eyebrows when new scientific or engineering breakthroughs achieve results of arguably same potential magnitude.

We just report it in small posts like this one…

Seeking SciNote, Biology: CRISPR


What do geneticists think will be possible when the the new gene-splicing CRISPR is fully operational on patients?


For those of us unfamiliar, CRISPR is a revolutionary new genetic splicing technology. Gene splicing refers to modifications to a gene transcript that can result in different proteins being made from a single gene. Interestingly, CRISPR’s inception began when dairy scientists discovered that bacteria used to create yogurt (by transforming lactose into lactic acid) had incorporated snippets of benign viruses into its genome. To their surprise, the incorporated DNA would create toxic agents to thwart infective viruses. In 2007, dairy scientists realized that they could effectively fortify bacteria by adding spacer DNA, which does not code for any protein sequence, from a virus. Then, five years later, as Time Magazine writer Alice Park skilfully describes, professors Jennifer Doudna and Emanuelle Charpentier noticed “up to 40% of bacteria developed a particular genetic pattern in their genomes. What they found were sequences of genes immediately followed by the same sequence in reverse, known as palindromic sequences. Further, bits of random DNA bases cropped up after each such pairing and right before the next one. After the dairy bacteria transcribed its spacer DNA and palindromic sequence into RNA, it self-spliced those segments into shorter fragments, with an enzyme called CAS9”. As you may be wondering, CRISPR stands for “clustered regularly interspaced short palindromic repeats”.

It is important for us to emphasize the versatility of this method. In the 2007 article, Doudna and Charpentier go into depth regarding the many benefits of the new genetic technology. These include the potential to “systematically analyze gene functions in mammalian cells, study genomic rearrangements and the progression of cancers or other diseases, and potentially correct genetic mutations responsible for inherited disorders”. As you might imagine, this opens up possibilities that were previously science fiction. Currently, painful blood transfusions are commonplace in the treatment of many diseases such as sickle cell anemia. Sickle cell affects red blood cells, which are made by stem cells in bone marrow. Soon, Massachusetts Institute of Technology synthetic biologist Feng Zhang envisions that this will soon no longer be necessary. She predicts that after doctors extract some of the marrow, scientists will splice out the defective fragment of DNA using CRISPR from the removed stem cells, then bathe the cells in a solution containing the non-sickle-cell sequence. As the DNA repairs itself naturally, it picks up the correct sequence and incorporates it into the stem cell genomes. After this one-time procedure, the stem cells would give rise to more red blood cells with the healthy gene. Eventually, the blood system would be repopulated with normal cells.

The treatment of HIV using CRISPR would be very similar. In this potential treatment, “patients would provide a sample of blood stem cells from their bone marrow, which would be treated with CRISPR to remove the CCR5 gene, and these cells would be transplanted back to the patient. Since the bone marrow stem cells populate the entire blood and immune system, the patient would eventually have blood cells that were protected, or “immunized,” against HIV”.

Despite this extraordinary potential, no biological technology comes without serious ethical concerns. As Jennifer Douda says herself, CRISPR “really requires us to careful thought to how we employ such a tool: What are we trying to do with it, what are the appropriate applications, how can we use it safely?”

Check out her book The Stem Cell Hope for learning about the future of stem cell technology.

Park, Alice. “A New Gene-Splicing Technique.” 100 New Scientific Discoveries: Fascinating, Unbelievable and Mind-expanding Stories. New York, NY: TIME, 2014. 92-95. Print.

Park, Alice. “It May Be Possible To Prevent HIV Even Without a Vaccine.” Time. Time, 6 Nov. 2014. Web.

Doudna, Jennifer A., and Charpentier, Emmanuelle (2014). The new frontier of genome engineering with CRISPR-Cas9. Science, 346(6213), 1258096–1258096. doi:10.1126/science.1258096

Answered by: Teodora S., Expert Leader and Expert John M.

Edited by: Carrie K.