In a major breakthrough in kidney disease research, a team of Israeli scientists led by Dr. Karl Skorecki has isolated a genetic mutation that is linked to contracting the disease, the first step in developing a cure. He has also discovered genetic patterns which connect most Jews' ancestry to the region of the Near East.
Dr. Karl Skorecki is a nephrologist by profession. The only child of Holocaust survivors, Prof. Skorecki was born and raised in Toronto. He received his medical degree from the University of Toronto in 1977 and conducted his post-graduate clinical and research training in the U.S.. After a sabbatical at the Weizmann Institute in 1991, Prof. Skorecki and his family decided to make aliyah to Israel and he joined the Technion faculty in 1995. He has been engaged for the last 18 years in population genetics research in general and in relation to specific diseases. He shared his story with Israel National News.
"Kidney disease is very common," said Skorecki, "but there are different stages of its development. End stage kidney disease (ESKD) is the final and most lethal stage. Five thousand patients in Israel and 500,000 in the United States have ESKD. In most parts of the world, people don't have access to dialysis or transplantation, which are necessary to treat ESKD, and therefore do not live. For each person with ESKD, there are 10 other people with earlier stages of the disease, who suffer from many complications."
Even the more fortunate patients who have access to treatment are not immune to suffering. "On dialysis, even though it's life sustaining, there is still a short life expectancy and a hard life. Transplant patients also have reduced life expectancy and lowered quality of life. Therefore, it's important to find out why people develop kidney disease and see if it can be prevented," said Skorecki.
Skorecki's team began by looking for genetic clues, analyzing ethnic groups who have a much higher rate of kidney disease. "One of the important clues was the discovery that African American's have 4-5 times higher rate of ESKD than Americans of European and East Asian ancestry. Hispanic Americans also have a much higher percentage than those groups. It makes you think that there is something hereditary or genetic involved. Our group at the Technion Faculty of Medicine and the Rambam Medical Center in Haifa began researching African Americans and Ethiopians in Israel to see if there was a genetic link between the groups."
"We published a paper in 2006 with our findings. We showed that Ethiopians in Israel, unlike African Americans, are protected from kidney disease. We reasoned that maybe because humans originated in Africa, during the evolution, groups split. In Africa, you find more diversity of humanity than across the whole world. We reasoned that we might find a difference between East and West Africans."
"We looked at DNA markers across the whole genome, and we identified differences in the gene APOL-1 that encodes a protein that's involved in cholesterol and blood fat. It turns out that there is a West African mutation that occurred in this gene in Africa, that was specific to certain populations and became very prominent there. The APOL-1 mutation is responsible for many kinds of kidney disease. If we knew how to cure that mutation and block it, we could reduce kidney disease by 70 percent."
"Finally we had a handle on how to fix and control kidney disease. It's like a treasure hunt - and now we know where to dig. We are currently working with other groups around the world to find out how the APOL-1 mutation causes kidney disease. And hopefully we can develop a drug that will block it."
Skorecki explained the origin of the mutation. "The APOL-1 mutation protects against a form of African sleeping sickness, which is a deadly disease transmitted by the tsetse fly. There was probably an epidemic in the past that killed a lot of Africans, but those with the mutation survived. That's called 'evolutionary medicine', since now, those Africans who live elsewhere in the world are immune to sleeping sickness, an immunity they don't really need any more, but they have this negative side effect that they contract kidney disease as they grow older."
The Jewish Genome
Dr. Skorecki is also involved in another fascinating area of genetic research - Jewish population genetics. Here too, his team has made some remarkable recent discoveries.
"Fifteen years ago, I started getting interested in population genetics," said Skorecki. "My research on genetic markers of Kohanim (the Jewish priestly class) is well-documented, so I won't get into that. But if we fast forward to 2010, we (my team at the Technion, Rambam, and scientists from eight other countries) decided to look at the whole genome, and try to discover the ethnic roots of the Jewish people as a whole."
"What we showed in a nutshell, after studying 14 Jewish communities whose ancestors came from Europe, the Soviet Union, North Africa, the Middle East, and India, and compared them with non-Jews (with parentage from those countries), we found that Jews in 90 percent of the Diaspora showed shared ancestry, different ancestry from their host country population. We found that Jews share a surprising similarly of markers across the whole genome. In each community you can see an admixture with the local community. But what you can't miss is that the Jewish genome is most similar to the populations of the Levant: Lebanese, Palestinians, Druse, and Cypriots."
"What does that mean? It certainly doesn't fit with theories that Jews have nothing to do with the Near East. Theories that say Jews are from North Africa or Europe. The genetic evidence doesn't support the notion that there is no tie between Jews and the Near East."
"Long before there were Jews, Druse, or Palestinians in the Near East there were people living in Lebanon, Israel, Jordan and Syria. Judaism was founded when there were already people here. We are seeing that Jews are descended from people that became part of the Jewish people. So it's not surprising that they share similarities with people of the Levant, with Druse especially."