Proyek 1000 Genom

Amerika, Inggris dan Cina kini bekerja sama dalam Proyek 1000 Genom. Proyek ini bertujuan untuk memetakan genom manusia terbaru dengan data variasi DNA biomedis paling lengkap dan lebih detail menurut Richard Durbin dari Sanger Institute. Proyek ini melibatkan institusi Wellcome Trust Sanger Institute dari Inggris, National Human Genome Research Institute (NHGRI) dari Amerika, dan Beijing Genomics Institute-Shenzhen, Cina.

Proyek 1000 genom ini mungkin untuk dilakukan saat ini karena teknologi pengurutan genetika, bioinformatika dan teknik lainnya makin mengalami kemajuan. Dengan proyek ini upaya untuk menemukan faktor genetika yang terlibat dalam penyakit dan kesehatan manusia daapt dilakukan dengan lebih efektif lagi.

Perbedaan yang ada pada individu merupakan pengaruh dari satu persen DNA, sehingga dengan riset dalam 1000 genom ini, informasi mengenai DNA akan lebih mendetail. Perbedaan satu persen pada DNA sering kali bertanggung jawab atas perbedaan dalam kerentanan terhadap penyakit dan reaksi pengobatan. Ilmuwan telah mendaftarkan puluhan wilayah variasi genom manusia yang spesifik (haplotipe) dan mengasosiasikannya dengan penyakit umum, seperti penyakit jantung koroner, kanker payudara, arthritics, dan penyakit akibat penuaan.

Peta DNA yang berhasil disusun tahun 2000 lalu masih belum terlalu detail, oleh karena itu ilmuwan ingin mengembangkannya lagi agar peta DNA yang ada saat ini menjadi lebih detail dan gambaran genom akan menjadi lebih jelas dalam menemukan faktor genetika suatu penyakit.

Proyek ini akan memetakan DNA dari beragam kelompok etnis yang spesifik, termasuk Yoruba di Ibadan, Nigeria; Chinese di Denver, Colorado; Chinese di Beijing; Toscani di Italia, India Gujarati di Houston, Texas; orang Meksiko di Los Angeles; serta warga keturunan Afrika di barat daya Amerika Serikat.

Dengan memanfaatkan teknologi sequencing dan metode komputasional terbaru, diharapkan dapat memberikan peta genom lengkap bagi ilmuwan biomedis, yang akan memaparkan segala bentuk variasi sampai tingkat satu persen dan ini akan mengubah cara ilmuwan untuk mempelajari penyakit genetis kata Francis Collins, wakil NHGRI.

Tempo Interaktif

Genetic Variant Predicts Heart Disease Risk

By Apoorva Mandavilli

Testing for a genetic variation could predict the likelihood that a patient will respond well to certain statins. But some researchers say it's too soon to use the variation to determine treatment.

Researchers from Celera reported yesterday in the Journal of the American College of Cardiology that a single substitution in the sequence of a gene called KIF6 makes people both more susceptible to heart attacks and more responsive to certain drugs that lower cholesterol. Though there is no known biological explanation linking the variation to heart disease, the study found that it increases the risk of heart attacks and strokes by 55 percent.

Celera, the company best known for sequencing the human genome, examined 35 single-nucleotide polymorphisms (SNPs) in 30,000 patients. Of those, "KIF6 is by far the most significant," says Thomas J. White, chief scientific officer at Celera. In fact, nearly 60 percent of the study population was found to carry the KIF6 variant. (According to the study, these findings take into account other factors, such as smoking, high blood pressure, and cholesterol levels.)

The researchers also found that carriers of the KIF6 variant responded better to the cholesterol-lowering drugs pravastatin (Pravachol) and atorvastatin (Lipitor). For example, among patients with the genetic variation, those who took pravastatin were 37 percent less likely to experience a heart attack than those who took the placebo. Those without the genetic variation who took the drug were only 14 percent less likely to experience a heart attack than those who took the placebo. Statins are big sellers for the pharmaceutical industry. In 2006, Lipitor, the world's best-selling drug, brought in $13 billion in global sales.

"This is one of the first studies to show an interaction with therapy" and genotype, says Marc Sabatine, professor of medicine at Harvard Medical School and a coauthor on one of the papers. "That is very exciting to see."

Surprisingly, the researchers found that KIF6 doesn't appear to work by lowering levels of LDL or "bad" cholesterol, the standard by which drugs used to prevent heart attacks are normally measured. White says that KIF6 may instead act by stabilizing "vulnerable plaques," which are particularly prone to triggering heart attacks.

Celera is developing a diagnostic that would test for the KIF6 variant and expects to launch it in a few months.

But some experts caution that it may be premature to introduce such diagnostic tests before there is further confirmation of KIF6's role in heart disease.

"Even if there are beneficial results, the standard should be that you need to document that knowing the genetic information is clinically useful," says Sekar Kathiresan, director of preventive cardiology at Massachusetts General Hospital.

Coronary heart disease caused one of every five deaths in the United States in 2006, so scientists have for quite some time been on the hunt for genes linked to heart attacks.

Rapid advances in technology have made that task much easier. At the same time, many of the genetic links to heart disease identified so far haven't held up on further analysis. At present, the only credible link is to a variant of the gene 9p21, identified last year by the Icelandic company deCODE Genetics, says Kathiresan. DeCODE offers a $200 diagnostic test for the 9p21 variant. (See "Gene Variant Linked to Heart Disease.")

A second gene, PCSK9, also looks promising, Kathiresan adds. "Nearly everything else is in the realm of 'possible but not definite.'"

It's good that KIF6 has been identified as a potential risk factor in several different studies, Kathiresan says. In each of the studies, he notes, there is less than a one-in-20 probability that the finding is a result of chance, which is generally considered an acceptable threshold for statistical significance.

But because of the high possibility of false positives, the threshold for genome-wide association studies should be much higher, on the order of one in 20 million, Kathiresan says. Both the 9p21 and the PCSK9 pass that test, he says.

"The key issue here is we don't know if these [KIF6 studies] are real results," Kathiresan says. "You need to show that it is clinically useful, and they have not crossed that threshold."

From here

Synthesizing a Genome from Scratch

By Emily Singer

In a technical tour de force, scientists at the J. Craig Venter Institute, in Rockville, MD, have synthesized the genome of the bacterium Mycoplasma genitalium entirely from scratch. The feat is a stepping stone in creating precisely engineered microbial machines capable of generating biofuels and performing other useful functions.

"It really is groundbreaking that you can synthetically build a genome for a bacterium," says Chris Voigt, a synthetic biologist at the University of California, San Francisco, who was not involved in the project. "It's bigger by orders of magnitude than what's been done before."

Biologists creating genetically engineered organisms now routinely order pieces of DNA that are 10,000 to 20,000 base pairs long--big enough to incorporate the genes for a single metabolic pathway. That allows researchers to engineer microbes that can perform specific tasks, but the ability to synthesize entire genomes could grant a whole new level of control over biological design. (See "Tumor-KillingBacteria.")

In the new study, scientists ordered 101 DNA fragments, encompassing the entire Mycoplasma genome, from commercial DNA synthesis companies. These fragments were designed so that each overlapped its neighboring sequence by a small amount; these overlapping stretches stick together, thanks to the chemical properties of DNA. Researchers then bound the fragments piece by piece, eventually generating the full 582,970 base pair Mycoplasma sequence. The findings were published Thursday in the online edition of Science.

"We consider this a second and significant step in a three-step process of our attempt to create the first synthetic organism," says Craig Venter, president of the Venter Institute. Venter and his colleagues ultimately want to create a minimal genome--one with the least number of genes needed to sustain life. Pinpointing the minimal genome will both shed light on key cellular processes and provide a base for designing sophisticated synthetic organisms. "We ultimately want to design cells that could function in a robust fashion to make unique biofuels," says Venter.

The researchers' next step will be to show that the synthetic genome functions as it should. "We have the whole genome assembled in a tube, but we need to transplant it into the cell of a different species to show that it can reboot the cell," says Hamilton Smith, a Nobel laureate who oversaw the project at the Venter Institute. Last year, Smith's group transplanted the genome of one species of Mycoplasma into another, demonstrating that this type of transplant is possible. (See "Transplanting a Genome.")

While the synthesis of a genome might be impressive from a scientific perspective, it is not yet a practical way to engineer microbes to make biofuels. Instead, several companies, including Synthetic Genomics, a biotech company founded by Venter to engineer microbes for energy, are using more traditional metabolic engineering techniques to generate fuel-producing bacteria. (See "Building Better Biofuels.") "What we're doing with synthetic chromosomes will be the design process for the future," says Venter.

Others in the field are excited about that prospect. "Being able to synthesize genomes opens up a new world," says Voigt. "You can build things on the scale of the genome." For example, he says, scientists are now engineering bacteria to perform different steps in the conversion of biomass into ethanol--one strain to break down the biomass, another to make ethanol. But ideally, scientists could put those processes together to create one organism that could eat biomass and spit out fuel. (See "The Price of Biofuels.") "That would require genome-scale design," Voigt says.

He likens the current project, which required multiple steps to glue the fragments together, to the last computers designed before automated manufacturing and microfabrication techniques were introduced. Similar advances are needed for more ambitious genome-synthesis projects. "We still need to develop 'one step' genome construction methods in order to reduce the costs and turn time of genome construction," says Drew Endy, a synthetic biologist at MIT.

From Here