Category Archives: Gene Medicine

Anthony L. Komaroff, M.D. Ask Dr. K

Dr. Komaroff

Dear Dr. K: In yesterday's column, a reader asked whether she should be tested for genes linked to Alzheimer's disease. Today, I thought I'd give you my view on the larger question: Will studies of our genes change the practice of medicine and improve our lives?

My answer: During my career, progress in human genetics has been greater than virtually anyone imagined. However, human genetics also has turned out to be much more complicated than people imagined. As a result, we have not moved as rapidly as we had hoped in changing medical practice.

I graduated from medical school in the late 1960s. We knew what human genes were made of DNA and we were beginning to understand how genes work. We had even identified a handful of genes that were linked to specific diseases. We assumed that disease resulted from an abnormality in the structure of a gene.

If I had asked any biologist on the day I graduated, "Will we ever know how many genes we have, and the exact structure of each gene?" I'll bet the answer would have been: "Not in my lifetime, or my children's lifetime."

They would have been wrong. Today we do know those answers. Indeed, some diseases are caused by an abnormality in the structure of genes. In fact, sometimes it is very simple: one particular change at one particular spot in just one particular gene leads to a specific disease. Sickle cell anemia is an example.

Unfortunately, with most diseases it's far from that simple. The first complexity: Most diseases are influenced by the structure of multiple genes, not just one. Examples are diabetes and high blood pressure.

The second complexity: Many diseases are explained not by an abnormal gene structure, but by whether genes are properly turned on or off. Most cancers fall into this category.

What do I mean by that? Every cell in our body has the same set of genes. Yet, a cell in our eye that sees light is different from a cell in our stomach that makes acid. Why? Because different genes are turned on in each type of cell.

Read more:
Ask Dr. K: Gene studies lead to better diagnoses

B.C.-based genome research published this week is expected to help doctors target treatment of lymphoma tumours.

We found novel mutations in a gene that have not been described before in any cancer, said Dr. Christian Steidl, a scientist at the BC Cancer Agency and a professor in the University of British Columbias Department of Pathology who led the study team. Its a first description with a state-of-the-art technology.

Published in the scientific journal Nature Genetics Sunday, the work is part of a worldwide effort to identify gene mutations in all kinds of cancer tumours so treatment can be tailored to an individuals specific illness.

Thats what we mean by personalized medicine, that we dont just use a drug off the shelf and hope it works. Thats what we currently do. We use a drug combination that is very unspecific. It works in a proportion of patients, but we dont really know why.

Projecting five to 10 years in the future, this type of research will be the foundation of the shift that will happen in personalized medicine, said Steidl.

The study took samples from healthy cells and cancer tumours in about 100 patients, which were then analyzed using advanced gene sequencing techniques that have become available in only the last few years. Lead researcher Jay Gunawardana, a PhD student in pathology at UBC, found about 20 per cent of patients with Hodgkins lymphoma and a subtype of non-Hodgkin lymphoma (primary mediastinal B cell lymphoma) carry the same genetic mutation. While there is currently no therapy that can fix the damage caused by this mutation in the gene called PTPN1, experts say it opens the door for other scientists to find a treatment now that the target is known.

The term lymphoma covers about 50 different types of cancer that affect the glands of the lymphatic system that control the bodys immune response. It is divided into two groups, Hodgkin and non-Hodgkin lymphoma, and is the fifth most common cancer type in Canada. Its cause is unknown and it is rising among young adults, according to Lymphoma Canada. Each year, about 8,800 Canadians are diagnosed with lymphoma and more than 3,000 die from the disease.

Dr. Andrew Zelenetz, a lymphoma specialist at Memorial Sloan Kettering Cancer Center in New York who has no connection to the study, said in a telephone interview the discovery is incremental in adding one more piece to the advancement of cancer treatments. But it is a significant contribution to the understanding of lymphoma as diverse rather than a single ailment.

We often mistakenly think of cancer as one thing, that there will be a single magical cure, he said. What genomics has taught us is that we can walk up to three people with the same lymphoma, but if we look inside we see its three different diseases that should be treated in different ways. Today we dont have all the treatment tools that we need, but we would like to get away from having to use poisons as chemotherapy. Wed like to get away from drugs that work non-specifically.

The scale of interest in this area of research can be seen in the International Cancer Genome Consortium which aims to create a catalogue of gene abnormalities found in tumours from 50 different types of cancer. In the U.S., the Cancer Genome Atlas project is focused on specific cancers of the brain, lung and ovary. So far, the missteps in gene coding that cause tumour growth are known in only a tiny fraction of the myriad types of cancer

Visit link:
New B.C. research lays the groundwork for personalized cancer treatment

By Callum Borchers/Globe Staff/February 12, 2014

A Cambridge biotechnology company launching Wednesday is taking aim at Parkinsons disease and ALS with a new gene therapy that deliberately infects patients with a virus.

The firm, Voyager Therapeutics, plans to use a class of viruses known as adeno-associated viruses as carriers to deliver vital proteins to the brain. Intentional infection may be counterintuitive, but the viruses used in the therapy are harmless to humans, making them ideal vehicles for moving proteins throughout the body, without troublesome side effects.

Boston venture capital firm Third Rock Ventures considered Voyagers research so promising that it invested $45 million to get the company off the ground, an unusually big bet on such an early stage life sciences firm.

Were just convinced that these viruses are going to be incredibly important delivery vehicles to different parts of the body and make a big difference in a lot of very serious disorders, said Third Rock cofounder Mark Levin, who will serve as Voyagers interim chief executive during the companys start-up phase.

The investment in Voyager marks Third Rocks latest foray into genetic medicine and the treatment of rare diseases. Bluebird bio of Cambridge, another gene therapy company in its portfolio, raised more than $100 million in an initial public stock offering last June. Bluebird is working on a treatment to slow the progression of a genetic brain disorder called childhood cerebral adrenoleukodystrophy, or CCALD.

In November, Third Rock joined two other venture firms in putting a combined $43 million behind a Cambridge start-up called Editas Medicine, which is developing a technique to edit faulty genes, such as those that cause Huntingtons disease and sickle cell anemia.

The investments reflect a broader belief among the scientific community that gene therapy could be the key to effectively treating some of the worlds most challenging disorders. Gene therapy techniques typically involve replacing a mutated gene with a healthy version or turning off a gene that causes disease.

Voyager plans to use adeno-associated viruses as carriers for both techniques. To treat Parkinsons, for instance, Voyager will use viruses to deliver a missing protein. For ALS, the viruses will help shut down a harmful protein.

Expecting gene therapy to produce cures for rare diseases might be unrealistic, Levin said, but the idea is to make a dramatic difference in patients lives.

Continue reading here:
Biotech start-up Voyager Therapeutics uses new gene therapy to attack diseases - Boston.com

Current ratings for: Schizophrenia risk increases 10-fold with genetic mutation

Public / Patient:

3.7 6 ratings

Health Professionals:

0 0 ratings

Researchers from Trinity College in Dublin, Ireland, have identified a risk gene mutation for schizophrenia and bipolar disorder that increases chances of developing the conditions by more than 10-fold. The team says they found this mutation is inherited from a distant but common European ancestor.

The international team, led by Prof. Aiden Corvin at Trinity's School of Medicine, says identifying this genetic mutation provides the medical community with insight into potential risk mechanisms for these disorders, the cause of which is poorly understood.

Results of their study are published in the journal Human Molecular Genetics.

Although treatments are available for schizophrenia and bipolar disorder, and evidence is increasingly suggesting these disorders share common genetic risk factors, the team says response to treatments varies and knowledge of the underlying biology has mostly eluded scientists.

Bipolar disorder affects around 4% of the world's population, and schizophrenia impacts around 51 million people around the world (about 1% of the world's population), the team says.

Go here to read the rest:
Schizophrenia risk increases 10-fold with genetic mutation

Gene mutation increases disorders risk tenfold

Friday, February 14, 2014

A rare gene mutation that increases the risk of developing schizophrenia or bipolar disorder more than tenfold has been identified by medical scientists at Trinity College Dublin.

Aiden Corvin, professor in psychiatry at the School of Medicine at Trinity and head of the Psychosis Research Group, said the Irish population may be advantageous for this type of gene discovery programme.

Because of the population history of Ireland, we as a people are more closely related than in more diverse populations, so we were able to pick up on this mutation in the Irish descendants of this person, said Prof Corvin. We believe more is to be found in the Irish population and this will help us to reach a more general understanding about the nature of these disorders.

Scientists examined blood samples from more than 1,564 Irish people with schizophrenia and 1,748 people without to look for small structural variations where genetic material is duplicated or deleted in the genome. They identified five patients where part of a gene called protein-activated kinase 7 was duplicated. Such duplications were not found in the control group.

Once the mutation was identified, researchers were able to check for it in schizophrenia and bipolar disorder samples from a European sample of more than 25,000 people. This confirmed that the duplication, although rare, increased risk of developing schizophrenia or bipolar disorder more than tenfold.

The duplications appeared similar in all cases and the authors found the duplication carriers are all likely to share a single mutation inherited from a distant, common European ancestor.

Prof Corvin said the finding demonstrates the power of gene discovery to provide new insights into poorly understood but potentially devastating disorders.

Irish Examiner Ltd. All rights reserved

Read the rest here:
Gene mutation increases disorders risk tenfold

Everyday our cells take in nutrients from food and convert them into the building blocks that make life possible. However, it has been challenging to pinpoint exactly how a single nutrient or vitamin changes gene expression and physiology. Scientists at the University of Massachusetts Medical School have developed a novel interspecies model system that allows these questions to be answered. In a study appearing in the journalCell, UMMS researchers use this new approach to show how bacterially supplied vitamin B12 changes gene expression, development and fertility in the model organismC. elegans.

In mammals, micronutrients are provided by a combination of diet and gut flora, said A.J. Marian Walhout, PhD, co-director of the Program in Systems Biology and professor of molecular medicine at UMMS and senior author of the study. Weve developed a powerful approach that can be used to unravel the complex interaction between nutrients, gene expression and physiology by systematically studying both the predator (worm) and the prey (bacteria). With it we can begin to answer important questions about how what we eat affects how we function.

The key to the study was a set of complimentary genetic screens performed on the transparent roundwormC. elegansand two kinds of bacteria that comprised the worms diet ComamonasandE. coli. In a pair of papers published last year, Walhout and colleagues described dramatic changes in gene expression between worms fed onlyComamonasand those fed onlyE. colibacteria. Linked to these genetic changes were profound physiological differences between the worms.Comamonas-fed worms developed faster and were less fertile than theirE. coli-fed counterparts.

By genetically dissecting the two bacteria and using a specialC. elegansstrain developed to sense changes to diet-related gene expression, Walhout and colleagues were able to zero in on a set of genes present inComamonasbut absent fromE. coli. Further testing confirmed that these genes were responsible for producing vitamin B12 inComamonasand it was the presence of the micronutrient that accounted for the genetic and physiological differences seen between the worms on different diets.

Importantly, Walhout found that vitamin B12 fulfills two important functions inC. elegans: It helps regulate development through the methionine/SAM cycle, which is needed for the production of cell membranes in new cells. It also alleviates potentially toxic buildups of the short-chain fatty acid propionic acid, which can alter gene expression or harm cells.

C. elegansfedE. coliare actually vitamin B12 deficient and this reflects only one natural state of the animal, said Walhout. BecauseE. colihas been the standard laboratory diet for decades it would be interesting to study other characteristics of the worm, such as behavior, mating and movement, on a vitamin B12 rich diet.

Walhout and colleagues say that this system can also be adapted to identify genetic and physiological changes caused by other micronutrients inC. elegans. With the proper human analogs, its possible that we could one day predict the precise interaction between diet, gene expression and physiology that occurs when we eat a carrot, hamburger, steak or any other food. Doing so might someday lead to new insights into a variety of conditions or diseases such as high cholesterol, heart disease, diabetes and obesity. It can also be used to explore the precise benefits of bacteria found in gut flora.

It turns out a single transgenic worm is a powerful tool for exploring the complex interaction between macro and micronutrients, gene expression and physiology, said Emma Watson, a doctoral student in the Walhout Lab and first author on theCellstudy.

Like Loading...

See the original post here:
B12 drives gene expression

Everyday our cells take in nutrients from food and convert them into the building blocks that make life possible. However, it has been challenging to pinpoint exactly how a single nutrient or vitamin changes gene expression and physiology. Scientists at the University of Massachusetts Medical School have developed a novel interspecies model system that allows these questions to be answered. In a study appearing in the journal Cell, UMMS researchers use this new approach to show how bacterially supplied vitamin B12 changes gene expression, development and fertility in the model organism C. elegans.

"In mammals, micronutrients are provided by a combination of diet and gut flora," said A.J. Marian Walhout, PhD, co-director of the Program in Systems Biology and professor of molecular medicine at UMMS and senior author of the study. "We've developed a powerful approach that can be used to unravel the complex interaction between nutrients, gene expression and physiology by systematically studying both the predator (worm) and the prey (bacteria). With it we can begin to answer important questions about how what we eat affects how we function."

The key to the study was a set of complimentary genetic screens performed on the transparent roundworm C. elegans and two kinds of bacteria that comprised the worm's diet -- Comamonas and E. coli. In a pair of papers published last year, Walhout and colleagues described dramatic changes in gene expression between worms fed only Comamonas and those fed only E. coli bacteria. Linked to these genetic changes were profound physiological differences between the worms. Comamonas-fed worms developed faster and were less fertile than their E. coli-fed counterparts.

By genetically dissecting the two bacteria and using a special C. elegans strain developed to sense changes to diet-related gene expression, Walhout and colleagues were able to zero in on a set of genes present in Comamonas but absent from E. coli. Further testing confirmed that these genes were responsible for producing vitamin B12 in Comamonas and it was the presence of the micronutrient that accounted for the genetic and physiological differences seen between the worms on different diets.

Importantly, Walhout found that vitamin B12 fulfills two important functions in C. elegans: It helps regulate development through the methionine/SAM cycle, which is needed for the production of cell membranes in new cells. It also alleviates potentially toxic buildups of the short-chain fatty acid propionic acid, which can alter gene expression or harm cells.

"C. elegans fed E. coli are actually vitamin B12 deficient and this reflects only one natural state of the animal," said Walhout. "Because E. coli has been the standard laboratory diet for decades it would be interesting to study other characteristics of the worm, such as behavior, mating and movement, on a vitamin B12 rich diet."

Walhout and colleagues say that this system can also be adapted to identify genetic and physiological changes caused by other micronutrients in C. elegans. With the proper human analogs, it's possible that we could one day predict the precise interaction between diet, gene expression and physiology that occurs when we eat a carrot, hamburger, steak or any other food. Doing so might someday lead to new insights into a variety of conditions or diseases such as high cholesterol, heart disease, diabetes and obesity. It can also be used to explore the precise benefits of bacteria found in gut flora.

"It turns out a single transgenic worm is a powerful tool for exploring the complex interaction between macro and micronutrients, gene expression and physiology," said Emma Watson, a doctoral student in the Walhout Lab and first author on the Cell study.

Story Source:

The above story is based on materials provided by University of Massachusetts Medical School. Note: Materials may be edited for content and length.

Read more from the original source:
Vitamin B12 accelerates worm development: New model for isolating the effects of nutrients on gene expression and ...

PUBLIC RELEASE DATE:

13-Feb-2014

Contact: Lisa Larson lisa.larson@umassmed.edu 508-856-2000 University of Massachusetts Medical School

WORCESTER, MA Everyday our cells take in nutrients from food and convert them into the building blocks that make life possible. However, it has been challenging to pinpoint exactly how a single nutrient or vitamin changes gene expression and physiology. Scientists at the University of Massachusetts Medical School have developed a novel interspecies model system that allows these questions to be answered. In a study appearing in the journal Cell, UMMS researchers use this new approach to show how bacterially supplied vitamin B12 changes gene expression, development and fertility in the model organism C. elegans.

"In mammals, micronutrients are provided by a combination of diet and gut flora," said A.J. Marian Walhout, PhD, co-director of the Program in Systems Biology and professor of molecular medicine at UMMS and senior author of the study. "We've developed a powerful approach that can be used to unravel the complex interaction between nutrients, gene expression and physiology by systematically studying both the predator (worm) and the prey (bacteria). With it we can begin to answer important questions about how what we eat affects how we function."

The key to the study was a set of complimentary genetic screens performed on the transparent roundworm C. elegans and two kinds of bacteria that comprised the worm's diet Comamonas and E. coli. In a pair of papers published last year, Walhout and colleagues described dramatic changes in gene expression between worms fed only Comamonas and those fed only E. coli bacteria. Linked to these genetic changes were profound physiological differences between the worms. Comamonas-fed worms developed faster and were less fertile than their E. coli-fed counterparts.

By genetically dissecting the two bacteria and using a special C. elegans strain developed to sense changes to diet-related gene expression, Walhout and colleagues were able to zero in on a set of genes present in Comamonas but absent from E. coli. Further testing confirmed that these genes were responsible for producing vitamin B12 in Comamonas and it was the presence of the micronutrient that accounted for the genetic and physiological differences seen between the worms on different diets.

Importantly, Walhout found that vitamin B12 fulfills two important functions in C. elegans: It helps regulate development through the methionine/SAM cycle, which is needed for the production of cell membranes in new cells. It also alleviates potentially toxic buildups of the short-chain fatty acid propionic acid, which can alter gene expression or harm cells.

"C. elegans fed E. coli are actually vitamin B12 deficient and this reflects only one natural state of the animal," said Walhout. "Because E. coli has been the standard laboratory diet for decades it would be interesting to study other characteristics of the worm, such as behavior, mating and movement, on a vitamin B12 rich diet."

Walhout and colleagues say that this system can also be adapted to identify genetic and physiological changes caused by other micronutrients in C. elegans. With the proper human analogs, it's possible that we could one day predict the precise interaction between diet, gene expression and physiology that occurs when we eat a carrot, hamburger, steak or any other food. Doing so might someday lead to new insights into a variety of conditions or diseases such as high cholesterol, heart disease, diabetes and obesity. It can also be used to explore the precise benefits of bacteria found in gut flora.

Originally posted here:
Vitamin B12 accelerates worm development

THURSDAY, Oct. 24 (HealthDay News) -- A specific genetic variant might help explain why eating red and processed meat is associated with an increased risk of colon cancer, a small, new study contends.

The study also found that another genetic variant might play a role in the lower risk of colorectal cancer associated with eating vegetables, fruits and fiber.

The findings could have public health significance since diet is a modifiable risk factor for this type of cancer, the researchers said.

The study included more than 9,000 people with colorectal cancer and a similar-sized group of people without cancer. The investigators said they found a significant interaction between the genetic variant known as rs4143094 and processed meat consumption. This variant is located in a chromosome region that includes GATA3, a gene previously linked to several forms of cancer.

Another significant diet-gene link was found in the genetic variant rs1269486, which was associated with a reduced risk of colorectal cancer, according to the study. It is scheduled for presentation Thursday at the annual meeting of the American Society of Human Genetics, in Boston.

How specific foods affect genes and colorectal cancer risk is unknown, but the digestion of processed meat may cause inflammation or immune system responses that might trigger tumor development, the researchers said.

It's believed that genetics, lifestyle and environment contribute to colorectal cancer risk.

"It is conceivable that selected individuals at higher risk of colorectal cancer based on genomic profiling could be targeted for screening, diet modification and other prevention strategies," study coauthor Jane Figueiredo, an assistant professor of preventive medicine at the University of Southern California, said in a society news release.

This study was presented at a medical meeting, so the findings should be viewed as preliminary until published in a peer-reviewed journal.

More information

See the rest here:
Gene may explain link between meat and colon cancer risk

India's versatile space programme has potential to significantly improve health care through tele-medicine and gene therapy which will go a long way in providing affordable treatment to large section of people, former ISRO chairman K Kasturirangan said today.

Delivering the 13th Dharma Vira Oration organised by Sir Ganga Ram Hospital, the eminent scientist, who had steered ISRO's space programme as its head from 1994 to 2003, said spin offs from satellite technology can be used extensively to enhance the health care sector in a big way.

"The experience from human space flight has led to several interesting ground based application such as artificial heart, kidney dialysis, invisible braces, sun glasses as well as other bio-medical instruments," Kasturirangan said while explaining possible applications of space technology in the health care sector.

Noting that tele-medicine could be a potential tool for improving the health care facilities across the country, he said it will cut the cost of medical treatment and at the same time ensure quality services, particularly to people in rural areas.

Kasturirangan, who is a member of the Planning Commission, said ISRO has provided connectivity to nearly 400 rural hospitals with 60 super specialty hospitals in the country so far.

Elaborating on the use of various satellite-related innovations in health sector, Kasturirangan said space imaging techniques can be helpful for early detection of cancer, cardiovascular disease and heart surgery.

He said continuous monitoring of astronaut's heart in space can be of great help to similar needs on the ground.

Ashok Chandra, Chairman of Sir Ganga Ram Trust Society paid tributes to Dharma Vira, saying his vision of involving doctors in the day to day running of the hospital have paid rich dividends.

"We are trying to fulfil his dream by providing quality, affordable health care to all sections of our society," said D S Rana, Chairman of Board of Management of the hospital said.

In his address titled 'Space: An Innovative Tool for Serving Human Kind' Kasturirangan also outlined some futuristic developments involving the 'bio-capsules' to reduce the effect of high radiation levels, treating diabetes and brain cancer as well as their use in gene therapy.

Excerpt from:
Space Programme Can Improve Health Care: Ex-ISRO Chief