Stem cells driven into selective suicide

The term “stem cell” is increasingly stretchy. This is one way to get rid of a particular Read more

The blue spot: where seeds of destruction begin

Learn more about the locus coeruleus, a "canary in the coal Read more

Complexity of NMDA receptor drug discovery target revealed

GluN2C heterotrimer dominant in cerebellum + thalamus -- possibly important target for Read more

Department of Human Genetics

Gene duplication leads to obesity in childhood syndrome

A team of researchers has discovered a genetic syndrome that causes childhood obesity, intellectual disability and seizures. The syndrome comes from an “unbalanced” chromosomal translocation: affected individuals have additional copies of genes from one chromosome and fewer copies of genes from another.

The results were published this week in Proceedings of the National Academy of Sciences, Early Edition.

Katie Rudd, PhD, assistant professor of human http://www.raybanoutletes.com/ genetics at Emory University School of Medicine, is senior author of the paper. Research specialist Ian Goldlust, now a graduate student in the NIH-Oxford-Cambridge Scholars Program, is the first author. Co-authors include investigators from around the USA and Australia.

Rudd’s team was able to connect the contribution of one gene, GNB3, among many involved in the translocation, to the obesity aspect of the syndrome. Her lab created a mouse model with an extra copy of the GNB3 gene and found that the mice are obese. The mice are on average 6 percent (males) or 10 percent (females) heavier.

Rudd says her work was greatly assisted by collaboration with the Unique Rare Chromosome Disorder Support Group, a UK-based charity. Within Unique, a few parents had together found that their children had translocations involving the same chromosomes and similar symptoms. They contacted Rudd and helped her find additional affected families. Her study includes seven unrelated patients.

“It really was a group effort, and Unique was the linchpin,” she says. “Managing to find seven families with exactly the same rare translocation would have been extremely difficult otherwise.”

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Alphabet of modified DNA keeps expanding

Move over, A, G, C and T. The alphabet of epigenetic DNA modifications keeps getting longer.

A year ago, we described research on previously unseen information in the genetic code using this metaphor:

Imagine reading an entire book, but then realizing that your glasses did not allow you to distinguish “g” from “q.” What details did you miss?

Geneticists faced a similar problem with the recent discovery of a “sixth nucleotide” in the DNA alphabet. Two modifications of cytosine, one of the four bases http://www.raybani.com/ that make up DNA, look almost the same but mean different things. But scientists lacked a way of reading DNA, letter by letter, and detecting precisely where these modifications are found in particular tissues or cell types.

Now, a team… has developed and tested a technique to accomplish this task.

Well, Emory geneticist Peng Jin and his collaborator Chuan He at the University of Chicago are at it again.

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Cilia = not silly

Please check out the news story on “Cilia guide neuronal migration in  developing brain,” illustrating the dynamic role played by cilia. Cilia are tiny hair-like structures on the surfaces of cells, but in the brain they are acting more like radio antennae.

In developing mouse embryos, Emory and UNC researchers were able to see cilia extending and retracting as neurons migrate. The cilia appear to be receiving signals needed for neurons to find their places.

The Developmental Cell paper is here. As a bonus, we have a video featuring two of the paper’s authors, geneticist Tamara Caspary and “Neurotypical?” blogger Laura Mariani, a graduate student in Caspary’s lab.

Posted on by Quinn Eastman in Uncategorized Leave a comment

Flexibility and forgiveness during embryonic development

Geneticist Tamara Caspary’s laboratory has a recent paper in the journal Development showing how a developing mammalian embryo can correct a mispatterned neural tube over time. Former Genetics + Molecular Biology graduate student Chen-Ying Su, now a postdoctoral fellow at the Fred Hutchinson Cancer Research Center in Seattle, is the first author of the paper.

A molecule called “Sonic Hedgehog” is needed for proper patterning of the brain, spinal cord and eyes – it provides signals to the cells in the embryo, telling them what to become. Mutations that enhance Sonic Hedgehog signaling can lead to neural tube defects, some of the most common birth defects in humans, while those that diminish it can lead to holoprosencephaly, malformations of the brain and face. However, the majority of neural tube defects such as spina bifida do not come solely as a result of genetics – doctors think that getting enough (and possibly, not too much) of the B vitamin folic acid can prevent most of them.

Red = motor neuron precursor, green = later motor neuron marker
Mutation of Arl13b causes expansion of motor neurons (B and J)
Later deletion causes temporary expansion (C), corrected two days later (K)

Su and her colleagues examined mouse development in a situation where patterning of the neural tube is disrupted for a short time, because of a deletion in a gene (Arl13b), which helps to carry out Sonic Hedgehog’s instructions.

If Arl13b is not working starting from the beginning of development, embryos have an expansion of motor neurons, at the expense of other types of cells. The mutation leads to an open neural tube as well as abnormal eye, heart and limb development. However, if the deletion of Arl13b occurs on the ninth day, the embryo can recover proper patterning over the next few days. Mouse pregnancies last roughly three weeks.

Caspary says that while the relationship between Hedgehog signaling and neural tube defects is complicated, her lab’s recent work “does help define the time window during which we could non-surgically correct neural tube defects in utero.”

“In addition, it points to the importance of what we call “plasticity”- that cells can make incorrect decisions and correct them if still in a competency window, much like we think of adolescence,” she says. “It hints at the promise of stem cell research, that cells might be coaxed into other fates even though they start expressing tissue-specific markers. And it shows that the embryo is still much better at it than we are in a tissue culture dish.”

Posted on by Quinn Eastman in Uncategorized 1 Comment

The face behind a case

Last week Emory posted a news item about a case report published in the American Journal of Human Genetics. The paper described how geneticists at Emory, in cooperation with Sanford Burnham Medical Research Institute in San Diego, used “whole exome sequencing” — a sort of executive summary scan of the genome — to find the cause of a metabolic disease in a young boy.

The case was an illustration of the trend of whole exome sequencing, which is starting to enter clinical practice as a diagnostic technology. A photo of the patient, courtesy of his parents and Sanford Burnham, is a powerful reminder that within every case report, there’s a real person’s history.

Courtesy of Heather Buschman

“Over the years, we’ve come to know many families and their kids with glycosylation disorders. Here we can tell them their boy is a true ‘trail-blazer’ for this new disease,” says Hudson Freeze, director of the Genetic Disease program at Sanford Burnham. “Their smiles—that’s our bonus checks.”

Posted on by Quinn Eastman in Uncategorized Leave a comment
« Previous   1 2 3 4