genetics

Increased level of risk

Sheba Medical Centre recently published a study undertaken over three years by its department of obstetrics and gynecology in conjunction with Sheba Genetic Institute and the Genetics Institute in the Tel Aviv Sourasky Medical Centre, which found that women of Ashkenazi descent were twice as likely to have a baby born with Fragile X syndrome (FXS) compared to Jewish non-Ashkenazi women.

Nearly 600 female carriers of the FXS gene from various Jewish heritages participated in the study, which was published in the peer-reviewed publication Nature. Previously, it was known that only CGG repeats and AGG interruptions affect the risk for a child with FXS. This new research adds a third identifier, children of two Ashkenazi parents, allowing for better personalized genetic counselling for carriers who are trying to conceive.

FXS is the most common genetic cause of mental disability in an unborn child and causes intellectual disability, behavioural and learning challenges, and various physical characteristics. The prevalence of carriers in the Jewish population stands at about one in 150 women.

Dr. Noam Domniz of the IVF unit at Sheba Medical Centre said: “The new information from this study regarding the influence of ethnicity stresses the importance of providing more accurate and personally targeted genetic counseling to each woman, according to her personal level of risk. At Sheba, we aim to use this new approach to better evaluate each carrier’s risk level, empower them to make informed choices, leading to a clearer and safer road to motherhood.”

Jewish genes and cancer risk

photo - Amy Byer-Shainman — Amy Byer-Shainman (photo from BRCAinBC)

With the growth of ancestry services like 23andMe, we are more aware than ever of our genes and how important they are. What we may not know is how our Jewish ancestry puts us and our children at greater risk for health issues.

Join BRCAinBC for a virtual event Oct. 1, at 7 p.m., to learn about your Jewish genes and the tenfold increased risk for Jewish people for certain cancers, including breast, ovarian, aggressive prostate cancer, pancreatic cancer and melanoma. Not only will you learn more about your risk, but you will learn where and how you can get tested and what you can do to prevent cancer.

photo - Matt Seaton — Matt Seaton *(photo from BRCAinBC)*

BRCAinBC is a group of individuals concerned about the effect of the BRCA genes on the Jewish community in British Columbia. The project was born out of the realization that many members of the Jewish community are not aware of the risks of carrying the BRCA genes and the risk of genetically linked cancers – BRCA 1 and 2 is the code for variant mutations of two genes known to increase the lifetime risk of several serious cancers in both women and men.

Your Jewish Genes: A Virtual Learning Event will feature speakers from across North America, including Amy Byer-Shainman, aka “the BRCA Responder,” and author of Resurrection Lily: The BRCA Gene, Hereditary Cancer and Lifesaving Whispers from the Grandmother I Never Knew; Matt Seaton, peer navigator with FORCE (Facing Our Risk of Cancer Empowered); as well as members of the B.C. Cancer Agency’s Hereditary Cancer Program and High Risk Clinic, including Dr. Rona Cheifetz, surgical oncologist, and Allison Mindlin, genetic counselor.

photo - Dr. Rona Cheifetz — Dr. Rona Cheifetz *(photo from BRCAinBC)*

For more information about BRCA genes and BRCAinBC, visit brcainbc.ca. To register for the Your Jewish Genes event, go to yourjewishgeneswebinar.eventbrite.ca. Tickets are by $1, $18 or $36 donation towards the BRCAinBC bursary program, which supports access to genetic testing for Jewish people in British Columbia. No one will be turned away for lack of funds.

Trying to make access equal

Dr. Cheryl Rockman-Greenberg (photo from Rockman-Greenberg)

In the 1970s, when Dr. Cheryl Rockman-Greenberg was eyeing the budding field of genetics as a career, she had to become a pediatric doctor first. Now, Rockman-Greenberg counts her clinical background as a blessing, one that, today, geneticists no longer require.

“Having a strong background in clinical medicine certainly always helped me in my career, because the kind of genetics I was always interested in was in rare metabolic diseases,” said Rockman-Greenberg. “These are diseases often caused by enzyme deficiencies that go by very elaborate names. Having a good foundation in clinical medicine through pediatrics certainly helped me.”

Rockman-Greenberg, who lives in Winnipeg, was invited to speak at the city’s Congregation Shaarey Zedek Sisterhood Interfaith Luncheon on April 30.

“I learned that the luncheon was spearheaded through the sisterhood in many ways to promote information sharing between the faiths,” she said, noting that a purpose of the event is education and “to look at how we can build bridges between people of different faiths and not build walls.”

“From a global perspective,” she said, “I think it fits the themes of the interfaith luncheon. And, from a Jewish perspective, I’ve certainly been involved over the years, particularly with the National Council of Jewish Women, of increasing awareness of the importance of genes for health, and bringing together some of the advocacy groups in rare genetic disorders.

“I helped the National Council put out a brochure on carrier testing on new genetic disorders in the Ashkenazi Jewish population that has been extremely well-received worldwide. This information is always evolving.”

At the luncheon, Rockman-Greenberg was planning to discuss, among other things, Bill S-201, also known as the Genetic Non-Discrimination Act, which passed into law in Canada in 2017, though it is still being challenged by insurance companies in Quebec.

“This is a remarkable act in the sense that it does protect Canadians from the use of genetic test results outside of medical care and medical research,” Rockman-Greenberg told the Independent. “In other words, genetic test results do not have to be disclosed to insurance companies or employers. We’re one of many countries who have such legislation in place, and many people here have worked for years and years lobbying for similar legislation for Canada.”

Methods of genetic testing continue to advance, said Rockman-Greenberg. Tests that were nonexistent or very complicated to administer as recently as two decades ago can now be done quickly and inexpensively.

“The evolution has dramatically changed over the past 10 years, particularly in the sense that the techniques we use to diagnose genetic disease have dramatically changed – from studying one gene at a time, to being able to sequence the entire genome of an individual,” she explained.

When Rockman-Greenberg refers to “new genetics,” she is referring to the ability to offer state-of-the-art, revolutionary genetic testing that was not possible just 10 years ago. It is this access that Rockman-Greenberg is lobbying for now.

“Everybody doesn’t have the same access to the testing in Canada,” she said. “It’s certainly not uniform from province to province or within provinces. So, many people are very committed to ensuring there are strategies in place to promote fairness.

“Notwithstanding that, the legislation is going to protect people against disclosing information that is already in place. I think we are ahead of the game because we have this in place. But, we are not ahead of the game in making sure people are going to have access to new diagnostic testing and new therapeutics in a way that’s going to be equal across the board.”

Rockman-Greenberg’s focus on rare metabolic diseases means that she has witnessed firsthand the struggles to get specialty drugs approved through a system focused on the big diseases, such as diabetes and cancer.

“You may get a new drug for diabetes that will be approved and available for patients very quickly, whereas some of the new drugs for other diseases I treat can take years and years before they go through the approval process,” she said.

Rockman-Greenberg thought that the topic was an appropriate one for an interfaith gathering, “as everybody having the same chance to be successful is very important to me. I work with families and patient support groups to help remove barriers and help people feel empowered.”

She said, “There are many challenges in dealing with rare diseases and I try to work both sides: the patient side, as well as advocate for changes at the government level, to make sure there is fairness in access to new therapies.”

Rebeca Kuropatwa is a Winnipeg freelance writer.

Genetics or lifestyle?

Study brings hope for improving our health.

The question of nature versus nurture extends to our microbiome – the personal complement of mostly friendly bacteria we carry around with us. Study after study has found that our microbiome affects nearly every aspect of our health; and its microbial composition, which varies from individual to individual, may hold the key to everything from weight gain to moods.

Some microbiome researchers have suggested that this variation begins with differences in our genes, but a large-scale study conducted at the Weizmann Institute of Science challenges this idea and provides evidence that the connection between microbiome and health may be even more important than we thought.

Indeed, the working hypothesis has been that genetics plays a major role in determining microbiome variation among people. According to this view, our genes determine the environment our microbiome occupies, and each particular environment allows certain bacterial strains to thrive. However, the Weizmann researchers were surprised to discover that the host’s genetics play a very minor role in determining microbiome composition – only accounting for about two percent of the variation between populations.

The research was led by research students Daphna Rothschild, Dr. Omer Weissbrod and Dr. Elad Barkan from the lab of Prof. Eran Segal of the computer science and applied mathematics department, together with members of Prof. Eran Elinav’s group of the immunology department, all at the Weizmann Institute. Their findings, which were published last month in Nature, were based on a unique database of around 1,000 Israelis who had participated in a longitudinal study of personalized nutrition.

Israel has a highly diverse population, which presents an ideal experimental setting for investigating the effects of genetic differences. In addition to genetic data and microbiome composition, the information collected for each study participant included dietary habits, lifestyle, medications and additional measurements. The scientists analyzing this data concluded that diet and lifestyle are by far the most dominant factors shaping our microbiome composition.

If microbiome populations are not shaped by our genetics, how do they nonetheless interact with our genes to modify our health? The scientists investigated the connections between microbiome and the measurements in the database of cholesterol, weight, blood glucose levels and other clinical parameters. The study results were very surprising: for most of these clinical measures, the association with bacterial genomes was at least as strong as, and in some cases stronger than, the association with the host’s human genome.

According to the scientists, these findings provide solid evidence that understanding the factors that shape our microbiome may be key to understanding and treating many common health problems.

“We cannot change our genes,” said Segal, “but we now know that we can affect – and even reshape – the composition of the different kinds of bacteria we host in our bodies. So, the findings of our research are quite hopeful: they suggest that our microbiome could be a powerful means for improving our health.”

The field of microbiome research is relatively young; the database of 1,000 individuals collected at the Weizmann Institute is one of the most extensive in the world. Segal and Elinav believe that, over time, with the further addition of data to their study and those of others, these recent findings may be further validated, and the connection between our microbiome, our genetics and our health will become clearer.

Elinav’s research is supported by the Adelis Foundation; Andrew and Cynthia Adelson; the estate of Bernard Bishin; Valerie and Aaron Edelheit; the European Research Council; Jack N. Halpern; the Leona M. and Harry B. Helmsley Charitable Trust; the Bernard M. and Audrey Jaffe Foundation; the Else Kroener Fresenius Foundation; the Park Avenue Charitable Fund; the Lawrence and Sandra Post

Family Foundation; the Rising Tide Foundation; Vera and John Schwartz; Leesa Steinberg; and Yael and Rami Ungar. Elinav is the incumbent of the Sir Marc and Lady Tania Feldmann Professorial Chair.

Segal’s research is supported by the Adelis Foundation; Judith Benattar; the Carter Chapman Shreve Family Foundation; the Crown Human Genome Centre, which he heads; the European Research Council; Jack N. Halpern; the Else Kroener Fresenius Foundation; Donald and Susan Schwarz; and Leesa Steinberg.

For more on the work being done at the Weizmann Institute, visit wis-wander.weizmann.ac.il.

2017 Dan David Prize winners

Author Jamaica Kincaid is among the Dan David Prize winners this year. (photo from TAU via Ashernet)

Tel Aviv University (TAU) has announced the winners of this year’s Dan David Prize, which will be awarded at a ceremony at TAU on May 21. Sometimes referred to as “Israel’s Nobel Prize,” this year’s recipients are Swedish biologist Prof. Svante Pääbo, American geneticist Prof. David Reich, American author Jamaica Kincaid, Israeli author A.B. Yehoshua, American astrophysicists Prof. Neil Gehrels and Prof. Shrinivas Kulkarni, and Polish astronomer and astrophysicist Prof. Andrzej Udalski.

The prize is named after the late Dan David, an international businessman and philanthropist.

Born in Romania in 1929, David worked for Romanian TV and later became a press photographer. In 1960, he settled in Israel. A year later, he traveled to Europe. With a loan from a cousin, he won the franchise for the Photo-Me automated photography booths in certain countries, and opened branches in several European countries, as well as in Israel, and eventually took over the company.

In 2000, he founded the Dan David Foundation with a $100 million endowment. The first time the annual prize was awarded was in 2002. David’s aim was to reward those who have made a lasting impact on society and to help young students and entrepreneurs become the leaders and scholars of the future.

David died in London, England, in September 2011.

Research in genetics

Dr. Cheryl Rockman-Greenberg (photo from Dr. Cheryl Rockman-Greenberg)

“There are approximately 7,000 rare diseases, each individually very rare. But, when you look at them as an aggregate, rare genetic metabolic disorders, they affect approximately one in 15, or two million, Canadians.”

Although there are various ways to define what constitutes a “rare genetic disorder,” Winnipeg-based Dr. Cheryl Rockman-Greenberg told the Independent, “One definition is that a rare disease is one that only affects one in 12 or fewer individuals in the general population, or some have defined it as disorders affecting a maximum of 1,000 to 2,000 individuals.”

Rockman-Greenberg specializes in medical genetics and genetic metabolic disorders. She said rare diseases represent a disproportionally large percentage of Canada’s medical, health-care and pycho-social burden.

Children who have a genetic rare disease experience high morbidity and mortality in the first two years of life. Phenylketonuria (PKU) is one of the more well known and, before a newborn baby leaves a hospital, he/she undergoes a heel poke. According to the Mayo Clinic website, PKU is an “inherited disorder [that] causes an amino acid called phenylalanine to build up in your body. PKU is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine. Without the enzyme necessary to process phenylalanine, a dangerous buildup can develop when a person with PKU eats foods that are high in protein.”

“Every baby born in Manitoba is screened for a whole series of rare metabolic diseases,” said Rockman-Greenberg.

Newborn screening programs have been in place across Canada since the 1960s and have expanded over time as treatment options, and the ability to diagnose disorders right after a baby is born, have increased.

“PKU only affects one in 15,000 children, but it’s an important metabolic disorder,” said the doctor. “Untreated children with PKU have severe developmental problems.”

Through research, it was discovered that PKU can be controlled by providing a special diet and, if treatment is started early, any damage can be completely prevented.

“These are all hereditary disorders. These metabolic disorders I treat or that are screened for at birth are all caused by one single gene pair, where there is a mutation in both copies of the gene,” said Rockman-Greenberg.

“Remember, genes come in pairs as two copies of the gene. And, if there is a misprint in each copy, if the child has misprints in both copies of the gene, then that condition is manifested. The genetic abnormality is the most significant factor for what causes the signs and symptoms. The environment plays little role overall.”

In the last few decades, more resources have been put into research. A big step in this direction was in the United States, with the Orphan Drug Act of 1983, which gave incentive to companies to develop treatments for rare metabolic diseases. Canada does not yet have such a policy.

“If you can imagine developing a treatment when there may be 50 patients in the whole country,” said Rockman-Greenberg. “It’s, first of all, a very expensive venture. For the industry, it’s much more profitable to do a drug trial for a common disease that may affect thousands and thousands of people.”

Regardless, the number of drugs that have been developed by companies prepared to invest in the research of rare diseases has increased.

“For many of these rare diseases, there are or have been excellent clinical trials over the past decade,” said Rockman-Greenberg. “And when the clinical trials have shown that a treatment is effective and safe, then more and more of these drugs get licensed and become available to treat patients.

“And then industry has stepped in and shown a commitment for drug development. This has greatly increased the number of diseases, rare metabolic diseases, that were not amenable to treatment but now have the potential for an effective treatment. So, a lot of the barriers have been removed … [because of] good research by industry and basic research by university scientists.”

Another factor that has helped change the landscape is the development of national patient groups.

“Parents and patient groups are extremely effective,” said Rockman-Greenberg. “They have really brought together the rare disease community that, in the past, has been very fragmented. Now, there’s a national voice through the Canadian Organization for Rare Diseases (CORD), Canada’s national network for organizations representing all those with rare diseases.”

“There are many disorders – rare, ultra-rare diseases – where we had seen babies die early of the disease. Now, the potential of treatment, viable and good quality survival, good quality of life … that’s what being a doctor is all about.”

Of these changes that have enabled her to provide better care for patients, Rockman-Greenberg said, “It’s wonderful. There are many disorders – rare, ultra-rare diseases – where we had seen babies die early of the disease. Now, the potential of treatment, viable and good quality survival, good quality of life … that’s what being a doctor is all about.”

Looking ahead, Rockman-Greenberg is optimistic. “In general, there are more and more incentives for drug development for rare metabolic diseases, so I see the metabolic community continuing to participate in clinical trials,” she said. “The development of therapies and, then, another major role that we as doctors have is to help ensure that patients have access to these promising therapies.

“We have to make sure that there are programs in places in all the provinces and territories that are going to allow patients to have access to these treatments. So, there’s lots of work that needs to be done and physicians have to be part of this dialogue with industry, governments and stakeholders to ensure we can make real change for patients with rare diseases.

“It’s one thing to find the cause for a rare disease. It’s another thing to prove a treatment is effective through clinical trials. But, at the end of the day, we have to make sure patients who aren’t candidates for treatment trials have access to care.

“We need to make sure as many people as possible are aware of the existence of rare metabolic diseases and how complicated they are, what a burden these diseases have on the patients and their families, but also about the many programs being developed to help research and develop new treatments, and help them connect to patient support groups that assist rare-disease patients.”

Rockman-Greenberg is the director of the metabolic service and a clinical geneticist in the program in genetics and metabolism of the Winnipeg Regional Health Authority. She is also a professor in the department of pediatrics and child health, and the department of biochemistry and medical genetics at the University of Manitoba. She grew up in Montreal and moved to Winnipeg in 1978. In January 1979, she began working at Winnipeg Children’s Hospital. As both a pediatrician and medical geneticist, she sees patients throughout their lifespan.

Rebeca Kuropatwa is a Winnipeg freelance writer.