Genetic bottleneck responsible for dystonia in Ashkenazi Jews

Judy Siegel:

The genetic mutation that causes childhood-onset dystonia - which causes victims to move their muscles involuntarily - has been traced by a US genetic epidemiologist to a small area in Belarus.

According to researchers, the mutation was present in the small group of Belarus Jews who survived anti-Semitic oppression in the 17th century, creating a "genetic bottleneck." The Ashkenazi population then underwent a population explosion in the 18th century, producing a disproportionate number of carriers of the disease.

Historical events thus compounded a genetic accident and increased the incidence of the gene from one in 20 to one in four for Ashkenazi Jews who trace their roots to this part of Belarus.

The findings were reported by Dr. Susan Bressman, a genetics researcher at Yeshiva University's Albert Einstein College of Medicine in New York, speaking at YU's symposium on Torah Umadda (Torah and Science) in the World of Medicine in Jerusalem Monday night. Bressman, who has investigated a form of childhood-onset dystonia more common in Ashkenazi Jews than in any other ethnic group, credited Dr. Neil Risch of the University of California at San Francisco with tracing the source of the genetic mutation.

The event was chaired by the medical school's new dean, Dr. Allen Spiegel, who expressed the hope that its researchers would move from predicting genetic illnesses to discovering cures.

Bressman's research into Parkinson's disease has put the spotlight on Ashkenazi Jews and a group of North Africans of Arab descent. Both groups are disproportionate carriers of the LRRK2 G2019S mutation. This suggested that Ashkenazi Jews can trace their origins to the Middle East, along a timeline that seems to link the groups around the time of the destruction of the Second Temple in 70 CE, she said. Research was underway to check whether other ethnic groups who carry the same mutation might also share the same historic origin, she said.

Rapid progress in medical research reinforced the need for development of sophisticated ethical guidelines for its application, she said. Having identified the genetic mutations that established a predisposition toward both dystonia and Parkinson's, Bressman's team was now looking for modifier genes that would explain why only 30% of carriers go on to develop these diseases. She said he hoped this would bring them closer to finding cures.

Predisposition to genetic disease was explored by Rabbi Prof. Avraham Steinberg, senior pediatric neurologist and director of the medical ethics unit at Jerusalem's Shaare Zedek Hospital. He discussed when screening for such genes was justified. Judaism believes human beings had free will, but our genetic make-up determined some of our characteristics, said Israel Prize laureate Steinberg. Most genes were only partial determinants or establish predispositions that could be altered by our environment or overcome through our choices, including genetic treatments, he said.

Pre-implantation genetic diagnosis and implantation (PGD) was permitted by halacha (Jewish law) for serious single-gene and chromosomal disease, he said, however new and challenging ethical questions have been raised by recent research into adult-onset diseases such as breast cancer and Parkinson's.

The possibility of screening out embryos with these mutations already exists, said Steinberg. He suggested that one test that might be applied was whether the development of an implanted embryo would result in a happy and purposeful life. This standard might also be employed when a family wanted to choose the embryo that would give them a child who would provide the best genetic donor material for a sibling suffering from leukemia, for example, because that child would grow up to feel an added sense of purpose to their existence, he said.

Diseases: Torsion Dystonia

The Impact of Generalized Dystonia on the Jewish Community

Rare Ailment Occurs More in Ashkenazis

Dystonia in Ashkenazi Jews: clinical characterization of a founder mutation

On The Evolution Of Ashkenazi Jewish Intelligence

Overclocking

The Whole Side of It—An Interview with Neil Risch

Studies Casting New Light On Origin of Europe's Jews

A Population-Genetic Test of Founder Effects and Implications for Ashkenazi Jewish Diseases