“I had my genome sequenced,” Dr. Karl Skorecki said. “I didn’t find out anything about health related genes. But it’s important for someone my age and above to transmit it to the kids.”
Dr. Skorecki explained that a DNA sequence is a legacy of helpful information, particularly if there are genetic predispositions that have not yet led to disease. “Everyone should give their DNA sequence to the kids, and deposit their DNA for future use,” he said. “It will be more and more impactful.”
Dr. Skorecki is a professor at Technion — Israel Institute of Technology, where he directs the laboratory of molecular medicine, and talked to me at the “Jewish Genomics Evening: Heritage to Health,” held on November 19 at the New York Genome Center in lower Manhattan. The program was designed to “explore how the revolution in genetic research … has transformed the way we think about Jewish identity.”
A genome comprises a person’s entire set of genes, and it is responsible for that person’s physical makeup — a multitude of traits that are expressed in that person’s lifetime. Sequencing refers to reading the entire genetic code found in a person’s cells, in order to decode the DNA language. When DNA is sequenced it can be compared, genetic letter by letter, to sequences of other people and populations, leading to a better understanding of the genetic basis of disease, as well as migration and human history. President Bill Clinton and British Prime Minister Tony Blair announced a working draft of the first human genome sequence with much fanfare; it was completed in 2000 and cost almost $3 billion. Thanks to rapidly progressing technological breakthroughs, the cost of a complete human sequence has plummeted to about $1,500 per person.
The prospects of a “$1,000 sequence” has been greeted with excitement, anticipation, and some trepidation, since the collection of detailed personal data carries with it questions related to privacy as well as equal access to the technology. The New York Genome Center’s mission is to “implement advanced genomic research…in order to help solve diseases. We harness the diversity of New York’s institutions and people to drive scientific discoveries that will vastly improve clinical care — ethically, equitably and urgently.” The New York Genome Center, which was founded in 2010, moved into its $50 million downtown Manhattan facility in 2013. It is an independent, nonprofit consortium of “academic, medical and industry leaders across the globe…translating genomic research into clinical solutions for serious diseases.” Its 12 prestigious institutional founding members include the Albert Einstein College of Medicine, Columbia University, Memorial Sloan-Kettering Cancer Center, and the Rockefeller University.
The Jewish genomics evening brought together experts from the NYGC and other institutions to discuss the implications of genome sequencing for understanding unique aspects of Jewish genes, genealogy, and genetic disease in the Jewish community.
Professor Skorecki, who is a renal specialist (“My day job is kidney disease”), became involved in genomics research when he observed in his synagogue that modern day kohanim — Jews descended from the biblical high priest Aaron — are a diverse group, and include Ashkenazim as well as Sephardim. As a kohen himself, he wanted to pursue this issue at a genetic level. If all kohanim are descended from one man, he reasoned, then all male kohanim should carry a Y chromosome (which is transmitted from father to son) with similar genetic markers. His research in the late 1990s confirmed the common ancestry of many modern day kohanim, who share certain genetic sequences on their Y chromosomes.
The panelists of the evening were able to explore the question of Jewish genomics in more depth, because today we have access to the complete set of genes, not just a few markers on the Y chromosome. The NYGC’s Dr. Yaniv Erlich, who opened the program, asked, “Are we a group of people who like gefilte fish? Are we from Europe? Are we from the Levant?” We can learn about “ancestry and health from a genetic perspective,” he said.
Panelist and moderator Carl Zimmer, a columnist for the New York Times, said that he was initially asked to attend as a journalist, but his role became integral to the program. “When Yaniv asked ‘are you Jewish?’ I said, ‘It’s complicated. My father’s Jewish, my mother is not. I converted and got a bar mitzvah, so I guess I am.’” He became one of four Jews whose DNA was sequenced for the Jewish genomics evening.
Dr. Skorecki explained how genomics could be used historically. Since mutations, or genetic changes, occur with some regularity over time, the divergence from one person’s genome to another can be traced back to a common ancestor, and that timeline can be estimated in numbers of generations and years. For instance, he said, “we can date the founder [of the kohanim] to 104 generations back, which fits with the biblical idea of the Aaronite founder, whoever that person was.”
Panelist Cece Moore talked about how modern sequencing can delve into genealogical questions. Ms. Moore, who worked as a consultant on the PBS show “Finding Your Roots, with Henry Louis Gates, Jr.” and co-founded the Institute for Genetic Genealogy, said that genetic genealogy can approach sequence studies from three perspectives. Y chromosome DNA studies give insight into paternal lineage. Mitochondrial DNA studies document the lineage from mother to children (children inherit mitochondrial genes only from their mother), and autosomal DNA documents the transmission of all the genes from generation to generation.
Ms. Moore reported that through sequencing, “I discovered that I have distant Ashkenazi Jewish ancestry, which was not known in the family.
“I work with a lot of people of unknown parentage,” she added. Adoptees and people who were conceived using donor sperm or eggs who want to learn more about their genetic heritage can do so through DNA sequencing.
One case Ms. Moore reported involved a baby switched at birth about 100 years ago. “One family was Irish and the other Ashkenazi Jewish,” she said. It was the story of Alice Collins Plebuch, who began to explore her own genetic genealogy using an online DNA test. She expected to find that she was Irish, English, and Scottish, but the test revealed that she was 50 percent Ashkenazi Jewish. Her six siblings were tested and had the same results, leading them to speculate that one of their parents was switched at birth. Through genetic analysis and a dogged search of birth records, they learned that their father and another newborn were sent home with the wrong parents. They eventually made contact with the offspring of the other man, discovering long-lost blood relatives.
“It can be pretty shocking if you thought you were 100 percent Italian and find out you were donor conceived and are half Jewish,” Ms. Moore said. “There’s always something surprising and [the genome] shows more diversity than what people expect.”
Yaniv Erlich took a small device, an “illumina flow cell chip,” from his pocket, describing how it is used for sequencing. The device, which costs several thousand dollars, can sequence up to eight genomes. “From the ancestry point of view, you don’t have to choose,” Dr. Erlich said. “You can look at all the autosomal DNA and get one big picture. You can also look at the genetic variations, which can have profound effects on the health side — the clinical side.”
“We use these tools with archeology and history,” Dr. Skorecki said. A genetic bottleneck is when a group of people has been dramatically reduced in number, then expanded in later generations. “There were just a few hundred founders [of the Ashkenazi Jewish population] not that long ago,” he said. “If some of them carried a disease-causing mutation it would have been magnified.” Mutated genes responsible for such diseases as Tay Sachs, Canavan, and cystic fibrosis appear at a higher incidence in Ashkenazi Jewish populations because of the genetic bottleneck effect. Other populations, such as the Finns, carry a higher incidence of other genetic glitches, because of their own historic genetic bottlenecks.
Nathan Pearson, NYGC’s senior director of scientific engagement and public outreach, described four people’s genomic results. “There is no such thing as a pure genome,” he noted. Singer and song writer Jill Sobule’s DNA showed that she is 99 percent Ashkenazi and 1 percent “other.” Alisa Robbins Doctoroff, president of UJA-Federation of New York, had similar results, with 98 percent Ashkenazi Jewish and 2 percent “other Mediterranean.” Mitochondrial DNA research on these women suggested that their ancestors’ route of migration over tens of thousands of years took them from Africa through the Levant and into Europe.
Journalist A.J. Jacobs, a self-described guinea pig, relished the experience of DNA sequencing, but said he was disappointed with the results, which showed him to be 99.9 percent Ashkenazi Jewish and 0.1 percent other. “I wanted a little Roma, or Scandinavian,” he quipped.
Carl Zimmer’s DNA analysis showed more diversity. Autosomal analysis showed him to be 50 percent Ashkenazi Jewish, 35 percent Northern European, 7 percent Southwest European, and 8 percent Southern European. He always knew that his father is Jewish and his mother of English, German, and Irish descent, so only the Southern European contribution was surprising. “My mother is shaking her head in total refusal,” Mr. Zimmer said, smiling at his parents, who were sitting in the audience. “I always thought of myself as a mongrel. Clearly we have a lot more research to do.”
“Sometimes DNA turns up something that is not in the paper trail,” Ms. Moore said. “The DNA doesn’t lie. But sometimes the paper trail does. Carl Zimmer is 8 percent Southeastern European.” She said that the DNA could be from one great grandparent or from many lines further back. It is possible to do more analysis to reveal the origin or origins of that genetic line, she added.
Dr. Pearson revealed medical related findings from the four people whose DNA had been sequenced. “A.J. is a carrier of cystic fibrosis, but he has a unique variant, from France, not Ashkenazi. Carl Zimmer has an FMF variant — Familial Mediterranean Fever. Cece has no history of CF [cystic fibrosis] in her family but is a carrier for CF. Cece has Ashkenazi Jewish sequences, including this CF variant.”
“I recommend that you do carrier tests and pass on this information to your family,” Dr. Erlich said. When people discover that they are carriers, this information can empower them to make important decisions, and to inform family members of possible disease risks.
“Do it responsibly,” Dr. Skorecki cautioned. “There is a controversy about do-it-yourself genetic testing, since health phenotypes and genetic information need to be carefully considered. One thing I can pass on to my children is health information, coupled with my genetic sequence.”
“When I learned I was a carrier it was important to my family,” Ms. Moore said. “My nieces were tested and none were carriers. It made me a personal genomics advocate.”
Information on the New York Genome Center is online at www.nygenome.org. The phone number is (646) 977-7000, and it is at 101 Avenue of the Americas. Information on The Institute for Genetic Genealogy is at www.i4gg.org.
Dr. Miryam Z. Wahrman is professor of biology at William Paterson University and author of “The Hand Book: Surviving in a Germ-Filled World,” which explores how handwashing can reduce the risk of disease in health-care settings, homes, schools, the workplace, and anywhere else people spread germs.