See Spot run. See Lassie save Timmy from a well. See Tibetan Mastiffs climb 4,500 meters above sea level on the Tibetan Plateau. The ever-so-fluffy Tibetan Mastiff, which commonly serves as a guard dog for the plateau's residents, is able to breathe comfortably at high altitudes. Like the Tibetan people, Tibetan Mastiffs have adapted to air with less oxygen.

Ya-Ping Zhang and a team of scientists examined sets of genes from 32 Tibetan Mastiffs, 20 Chinese native dogs, and 14 wolves to investigate how the Mastiffs have adjusted. They looked for variations in the DNA sequence called single-nucleotide polymorphisms (SNPs, also pronounced simply as "snips"). The scientists genotyped the SNPs in the Mastiffs and compared them to the ones in the dogs and wolves.

After finding more than 120,000 SNPs, Zhang and the scientists identified 16 genes with signals of positive selection in the Tibetan Mastiff – 12 of these genes are connected to functions in the body that would help the canine adapt to high altitudes with low oxygen levels. Several of these genes are responsible for the building of hemoglobin, which helps transport oxygen through blood, and monitoring metabolism. Oxygen is required to process consumed food into energy, so efficient metabolizing means less oxygen is used. One of the genes, EPAS1, has also been linked to helping Tibetan humans adapt to high altitudes.

Scientists routinely seek to reprogram bacteria to produce proteins for drugs, biofuels and more, but they have struggled to get those bugs to follow orders. But a hidden feature of the genetic code, it turns out, could get bugs with the program. The feature controls how much of the desired protein bacteria produce, a team from the Wyss Institute for Biologically Inspired Engineering at Harvard University reported in the September 26 online issue of Science.
The findings could be a boon for biotechnologists, and they could help synthetic biologists reprogram bacteria to make new drugs and biological devices.
By combining high-speed "next-generation" DNA sequencing and DNA synthesis technologies, Sri Kosuri, Ph.D., a Wyss Institute staff scientist, George Church, Ph.D., a core faculty member at the Wyss Institute and professor of genetics at Harvard Medical School, and Daniel Goodman, a Wyss Institute graduate research fellow, found that using more rare words, or codons, near the start of a gene removes roadblocks to protein production.
"Now that we understand how rare codons control gene expression, we can better predict how to synthesize genes that make enzymes, drugs, or whatever you want to make in a cell," Kosuri said.
To produce a protein, a cell must first make working copies of the gene encoding it. These copies, called messenger RNA (mRNA), consist of a specific string of words, or codons. Each codon represents one of the 20 different amino acids that cells use to assemble proteins. But since the cell uses 61 codons to represent 20 amino acids, many codons have synonyms that represent the same amino acid.
In bacteria, as in books, some words are used more often than others, and molecular biologists have noticed over the last few years that rare codons appear more frequently near the start of a gene. What's more, genes whose opening sequences have more rare codons produce more protein than genes whose opening sequences do not.
No one knew for sure why rare codons had these effects, but many biologists suspected that they function as a highway on-ramp for ribosomes, the molecular machines that build proteins. According to this idea, called the codon ramp hypothesis, ribosomes wait on the on-ramp, then accelerate slowly along the mRNA highway, allowing the cell to make proteins with all deliberate speed. But without the on-ramp, the ribosomes gun it down the mRNA highway, then collide like bumper cars, causing traffic accidents that slow protein production. Other biologists suspected rare codons acted via different mechanisms. These include mRNA folding, which could create roadblocks for ribosomes that block the highway and slow protein production.
To see which ideas were correct, the three researchers used a high-speed, multiplexed method that they'd reported in August in The Proceedings of the National Academy of Sciences.
First, they tested how well rare codons activated genes by mass-producing 14,000 snippets of DNA with either common or rare codons; splicing them near the start of a gene that makes cells glow green, and inserting each of those hybrid genes into different bacteria. Then they grew those bugs, sorted them into bins based on how intensely they glowed, and sequenced the snippets to look for rare codons.
They found that genes that opened with rare codons consistently made more protein, and a single codon change could spur cells to make 60 times more protein.
"That's a big deal for the cell, especially if you want to pump out a lot of the protein you're making," Goodman said.
The results were also consistent with the codon-ramp hypothesis, which predicts that rare codons themselves, rather than folded mRNA, slow protein production. But the researchers also found that the more mRNA folded, the less of the corresponding protein it produced—a result that undermined the hypothesis.
To put the hypothesis to a definitive test, the Wyss team made and tested more than 14,000 mRNAs – including some with rare codons that didn't fold well, and others that folded well but had no rare codons. By quickly measuring protein production from each mRNA and analyzing the results statistically, they could separate the two effects.
The results showed clearly that RNA folding, not rare codons, controlled protein production, and that scientists can increase protein production by altering folding, Goodman said.
The new method could help resolve other thorny debates in molecular biology. "The combination of high-throughput synthesis and next-gen sequencing allows us to answer big, complicated questions that were previously impossible to tease apart," Church said.
"These findings on codon use could help scientists engineer bacteria more precisely than ever before, which is tremendous in itself, and they provide a way to greatly increase the efficiency of microbial manufacturing, which could have huge commercial value as well," said Wyss Institute Founding Director Don Ingber, M.D., Ph.D. "They also underscore the incredible value of the new automated technologies that have emerged from the Synthetic Biology Platform that George leads, which enable us to synthesize and analyze genes more rapidly than ever before."

Investigators at Massachusetts Eye and Ear and Harvard Medical School have published the most thorough description of gene expression in the human retina reported to date. In a study published today in the journal BMC Genomics, Drs. Michael Farkas, Eric Pierce and colleagues in the Ocular Genomics Institute (OGI) at Mass. Eye and Ear reported a complete catalog of the genes expressed in the retina.

The retina is the neural tissue in the back of the eye that initiates vision.  It is responsible to receiving light signals, converting them into neurologic signals and sending those signals to the brain so that we can see.  If one thinks of the eye as a camera, the retina in the “film” in the camera. For these studies, the investigators used a technique called RNA sequencing (RNA-seq) to identify all of the messenger RNAs (mRNAs) produced in the human retina.  The resulting catalog of expressed genes, or transcriptome, demonstrates that the majority of the 20,000+ genes in the human body are expressed in the retina.  This in itself is not surprising, because the retina is a complex tissue comprised of 60 cell types.

In a more surprising result, Dr. Farkas and colleagues identified almost 30,000 novel exons and over 100 potential novel genes that had not been identified previously. Exons are the portions of the genome that are used to encode proteins or other genetic elements.  The investigators validated almost 15,000 of these novel transcript features and found that more than 99 percent of them could be reproducibly detected. Several thousand of the novel exons appear to be used specifically in the retina.  In total, the newly detected mRNA sequence increased the number of exons identified in the human genome by 3 percent. 

“While this may not sound like a lot, it shows that there is more to discover about the human genome, and that each tissue may use distinct parts of the genome,” said Dr. Pierce, Director of the OGI and the Solman and Libe Friedman Associate Professor of Ophthalmology, Harvard Medical School.

This work is valuable to help scientists understand how the retina worksand how it is affected by disease. For example, Dr. Pierce and colleagues in the OGI study inherited retinal degenerations, which are common causes of vision loss. These diseases are caused by misspellings or mutations in genes that are needed for vision. To date, investigators have identified more than 200 retinal degeneration disease genes, but still can’t find the cause of disease for up to half of the patients affected by these disorders. Identification of new exons used in the retina may help find the cause of disease in these patients. 

Identifying the genetic cause of patients’ retinal degeneration has become especially important with the recent success of clinical trials of gene therapy for RPE65 Leber congenital amaurosis (LCA). As a follow-up to these initial proof-of-concept trials, clinical trials of gene therapy for four other genetic forms of inherited retinal degeneration are currently in progress. Further, studies in animal models have reported successful gene therapy for multiple additional genetic types of IRD. There is thus an unprecedented opportunity to translate research progress into provide sight preserving and/or restoring treatment to patients with retinal degenerative disorders.

About Massachusetts Eye and Ear 
Mass. Eye and Ear clinicians and scientists are driven by a mission to find cures for blindness, deafness and diseases of the head and neck.  After uniting with Schepens Eye Research Institute in 2011, Mass. Eye and Ear in Boston became the world's largest vision and hearing research center, offering hope and healing to patients everywhere through discovery and innovation.  Mass. Eye and Ear is a Harvard Medical School teaching hospital and trains future medical leaders in ophthalmology and otolaryngology, through residency as well as clinical and research fellowships.  Internationally acclaimed since its founding in 1824, Mass. Eye and Ear employs full-time, board-certified physicians who offer high-quality and affordable specialty care that ranges from the routine to the very complex.  U.S. News & World Report’s “Best Hospitals Survey” has consistently ranked the Mass. Eye and Ear Departments of Otolaryngology and Ophthalmology as among the top hospitals in the nation. Mass. Eye and Ear is home to the Ocular Genomics Institute which aims to translate the promise of personalized genomic medicine into clinical care for ophthalmic disorders. 

Bulgarian scientists have discovered a new disease. It is a neurological and is caused by mutation of genes, said Prof. Ivaylo Tarnev.

New diagnosis called autosomal recessive congenital ataxia. It is accompanied by oftalmopareza and mental retardation.

The disease is due to a mutation in a gene which encodes a metabotropic glutamate receptor 1 (mGluR1) on chromosome 6q24.

The results of the Bulgarian medics were published in the prestigious scientific journal American Journal of Human Genetics.

Three new genes that lead to hereditary diseases found Bulgarian doctors and geneticists. For the first time achievement was announced at the ongoing forum in Albena on "Genes, brain, intelligence, behavior."

Studies have been made over the past year and a half, despite the lack of state funding, the researchers were able to complete their work on the project. Describing the new neurological disease will lead to the exact diagnosis, and to the possibility of prophylaxis.

"In families where there is a risk of being born with the same desease, already possible to prenatal diagnostic and diagnostic counseling in these families. All this can prevent them from occurring in new patients in these families, "explained Dr. Ivaylo Tarnev from University Hospital" Aleksandrovksa. "

During the forum, the national consultant in medical genetics professor Ivo Kremenski will outline problems with the implementation of new genomic research into medical practice. Will be presented and advances in the treatment of brain tumors, genetics of behavior, the problems of people with autism.