A Gutsy Step Forward for Diabetes

Researchers at Columbia University’s Berrie Diabetes center may have found a way to treat people with type 1 diabetes using gastrointestinal (GI) cells. Dr. Accli’s lab has recently replicated a study previously conducted that used diabetic mice treated with genetically engineered GI cells. The study showed by turning off only a single gene, FOX01, GI cells became insulin-producing cells that could almost normalize a diabetic mouse’s glucose levels. The experiment proved successful with humans as well. By turning off FOX01, GI cells proved to be a more feasible option than insulin-producing cells created from embryonic and adult stem cells. This is due to the fact that the converted cells were able to release insulin only as a response to glucose levels. Dr. Accli is hopeful for a drug that can be used to inhibit FOX01 in GI cells to treat diabetics. Article

Turtle Draft-Genomes Yield Insight into Their Body Development and Evolution

The first genome wide phylogenetic analysis of two turtle species tackles the questions about the origin of the turtle’s unique anatomical features. Turtles have a unique exterior shell and skeletal layout that differs from that of their fellow tetrapods. Their carapace is a transformed vertebrae and ribs, their shoulder blades are ventral rather than dorsal, and their skulls lack temporal fenestra. These characteristics led to an analysis of their genome that found that turtles are closely related to Archosauria and that their morphological evolution was the cause of alterations in their signaling cascade. Investigations into their embryonic gene regulation led to the belief that they are morphologically similar to chickens, but have an hourglass-like divergence that shows where exactly (vertebrate phylotypic period) the structure of the shell begins to form.

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Research team unravels genetic mechanism underlying common SNP associated with blond hair in Europeans.

Guenther et al. publish in this week's Nature Genetics on their research demonstrating that a single nucleotide substitution in a transcription factor binding site upstream of the KITLG gene decreases the binding of the LEF1 transcription factor, thereby decreasing expression of the gene by ~20% and contributing to lightened pigmentation of the hair. Many genome wide association studies reveal associations between SNPs and phenotype, but discovering the exact genetic basis of these correlations remains challenging. This study provides a great example of painstaking effort by the research team to identify the causal SNP in a blond-associated haplotype and the necessary experimental validation of its functional impact in human cell lines and transgenic mice. Although this is an impressive achievement, as Hopi Hoekstra writes in a comment piece, it also demonstrates the challenges facing researchers in identifying and characterizing the impact of cis-reulgatory changes.

Also particularly notable about this paper is its citation of the work of YMAL lab member, Susan Walsh!

New Data Further Complicates Human Origins

Mitochondrial (mtRNA) testing of 17 individuals from the Sima de los Huesos, or “Bone Pit” archaeological site has further complicated the current understanding of human evolution. Previously, the site in Burgos, Spain has yielded 6,500 pieces of human skeletons, representing at least 28 individuals. These were classified as Homo heidelbergensis, the name given to the first humans who lived in Europe starting about 600,000 years ago. However, mitochondrial DNA testing found that these individuals had more similarities with another group of proto-humans, the Denisovans. The Denisovans and heidelbergensis were thought to have evolved distinct mtDNA prior to migration. Thus finding Denisovan mtRNA in Spain is contradictory, as they were only found in Asia. In the words of the article, these new findings only prove that "building a coherent story out of [human evolution] is a long-winded business.”

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Genetic Diversity In Mexico

Researchers have shown that there is substantial genetic variation between ethnic groups in Mexico.  Generations of geographic separation have fostered differences between populations, and the data have allowed the authors to come to interesting and medically relevant conclusions.  First, the variation has made it possible to genetically map historical movements between the populations.  Mexican history has, for many Mexican residents, generated a medley of ancestry including indigenous, European and African descent.  Second, understanding this variation and its sources allows doctors to know genetic risks for the relevant populations.  For example, the researchers identified a gene variant that affects lung function, and there are direct diagnostic implications.

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Genome Sequencing Beats Cancer

The time and costs of genome sequencing are getting smaller every year. Within 5 to 10 years, cancer treatments tailored to individuals may be commonplace.

Dr. Lukas Wartman, a leukemia doctor, was diagnosed in 2003 with Acute Lymphoblastic Lymphoma. After his second relapse in 2011, the future seemed grim. As a last resort, his colleagues at Washington University in St. Louis decided to sequence his entire genome, exome, and RNA sequence. The university was able to pool its resources, and it took only a few weeks to extract and analysis his genetic information. After determining through RNA analysis that his FLT3 gene was over-expressed in cancer cells, his doctors prescribed Sutent, a drug made by Pfizer. Two weeks after taking this drug, Dr. Wartman's bone marrow biopsy and flow cytometry came back clean. Dr. Wartman then underwent another bone marrow transplant. As of September 2013, the cancer has not returned.

http://www.nytimes.com/2012/07/08/health/in-gene-sequencing-treatment-for-leukemia-glimpses-of-the-future.html?_r=2&pagewanted=all&

http://genome.wustl.edu/articles/detail/doctor-survives-cancer-he-studies/

Blind mole rat genome sequenced

A new Nature Communications paper examines the comparative genomics of the blind mole rat. Blind mole rats show unusual resistance to cancer, and this study identified some specific protein changes (at gene p53) that might underlie this medically-relevant trait.  Even more interesting -- the study found genomic signatures of adaptations to living underground. For example, changes to circadian rhythm genes (CLOCK) show interesting patterns of convergent evolution with the distantly-related naked mole rat.