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Welcome to The Visible Embryo, a comprehensive educational resource on human development from conception to birth.

The Visible Embryo provides visual references for changes in fetal development throughout pregnancy and can be navigated via fetal development or maternal changes.

The National Institutes of Child Health and Human Development awarded Phase I and Phase II Small Business Innovative Research Grants to develop The Visible Embryo. Initally designed to evaluate the internet as a teaching tool for first year medical students, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than one million visitors each month.

Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development
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Home | Pregnancy Timeline | News Alerts |News Archive Feb 13, 2014

 

Expiditing the exchange of one single letter of the human genetic code
may pave the way for treating genetic diseases.






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Genome editing goes hi-fi

Innovative technique to edit genetic code — one letter at a time — paves the way to potentially cure genetic diseases.

Biology can be cruel. Sometimes simply a one-letter change in the human genetic code is the difference between health and deadly disease. Even though doctors and scientists have long studied disorders caused by these tiny changes, replicating them to study in human stem cells has proven challenging.

"Advances in human genetics have led to the discovery of hundreds of genetic changes linked to disease, but until now we've lacked an efficient means of studying them," explained Bruce Conklin, MD, lead investigator at the Gladstone Institutes. "To meet this challenge, we must have the capability to engineer the human genome, one letter at a time, with tools that are efficient, robust and accurate. And the method that we outline in our study does just that."

Now, scientists at the Gladstone Institutes have found a way to efficiently edit the human genome one letter at a time — not only boosting researchers' ability to model human disease, but paving the way for therapies to fix the so-called 'bugs' in a patient's genetic code.

In the latest issue of Nature Methods, the research team describes how they captured rare genetic mutations that cause disease, as well as fix them, one of science and medicine's most pressing problems.

Their pioneering technique highlights the type of out-of-the-box thinking often critical to scientific success. One of the major challenges preventing researchers from efficiently generating and studying genetic diseases is that the task of finding and studying them is so labor-intensive.


"For our method to work, we needed to find a way to efficiently identify a single mutation among hundreds of normal, healthy cells, So we designed a special fluorescent probe to distinguish a mutated sequence from an original sequence.

"We were then able to sort through sets of sequences and detect mutant cells — even when those cells were as few as one in every thousand cells. This is a level of sensitivity more than one hundred times greater than traditional methods."

Yuichiro Miyaoka, PhD, lead author and Gladstone research scientist


The research team first used an already available and highly advanced gene-editing technique called TALEN to make single letter edits to the genome. Athough TALEN, and other similarly advanced tools, are able to make a clean edit, such edits are very rare. Gene-editing techniques leave a 'scar' on newly edited genomes, and such scars can affect subsequent generations of cells, complicating future analysis.

So the Gladstone scientists designed a pair of TALENs to more precisely target a single letter site on a gene with the least disruption to the gene. They then combined this technique with fluorescent probes to identify the newly inserted gene "letter." The iPS cells used for the single letter insertion were derived from the skin cells of human patients.


"Our method provides a novel way to capture and amplify specific mutations that are normally exceedingly rare. Our high-efficiency, high-fidelity method could be the basis for the next phase of human genetics research. Some of the most devastating diseases are caused by the tiniest of genetic changes.

"But we are hopeful that our technique of amending the human genome as if it were lines of computer code, could one day be used to reverse harmful mutations, essentially repairing damaged code."

Bruce Conklin, MD, lead investigator at the Gladstone Institutes


"Now that powerful gene-editing tools, such as TALENs, are readily available, the next step is to streamline their implementation into stem cell research," said Dirk Hockemeyer, PhD, assistant professor of molecular and cellular biology at the University of California, Berkeley, who was not involved in this study. "This process will be greatly facilitated by the method described by Dr. Conklin and colleagues."

Nature Methods (2014) doi:10.1038/nmeth.2840
Received 06 July 2013 Accepted 17 December 2013 Published online 09 February 2014

Article metrics
Precise editing of human genomes in pluripotent stem cells by homology-driven repair of targeted nuclease–induced cleavage has been hindered by the difficulty of isolating rare clones. We developed an efficient method to capture rare mutational events, enabling isolation of mutant lines with single-base substitutions without antibiotic selection. This method facilitates efficient induction or reversion of mutations associated with human disease in isogenic human induced pluripotent stem cells.

Authors
Yuichiro Miyaoka, Amanda H Chan, Luke M Judge, Jennie Yoo, Miller Huang, Trieu D Nguyen, Paweena P Lizarraga, Po-Lin So & Bruce R Conklin


Other Gladstone scientists who contributed to this research are: Amanda Chan, Luke Judge, MD, PhD, Jennie Yoo, Trieu Nguyen, Paweena Lizarraga and Po-Lin So, PhD. Many organizations provided support for this research, including the Japan Society for the Promotion of Science, the Uehara Memorial Foundation, the California Institute for Regenerative Medicine, the National Heart, Lung, and Blood Institute, the Roddenberry Foundation and the National Institutes of Health.

About the Gladstone Institutes
Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.