Although they probably weren't named Sarah, Rebekah, Rachel and Leah, four Jewish "founding mothers" who lived in Europe 1,000 years ago have been credited with being the ancestors of nearly half of all Ashkenazi Jews, who constitute the majority of the current Jewish population. About 3.5 million people - or 40 percent of Ashkenazi Jews currently alive - are descended from these matriarchs, who were among a small group, probably after migrating from the Middle East, according to the Israeli researchers, who also provide evidence of shared maternal ancestry between Ashkenazi and non-Ashkenazi (Sephardi and Oriental) Jews. The studies that led to these findings were performed by Dr. Doron Behar as part of his doctoral thesis, and were done under the supervision of Prof. Karl Skorecki of the Rappaport Faculty of Medicine and Research Institute at the Technion-Israel Institute of Technology and at the Rambam Medical Center in Haifa. Skorecki is best known for his 1997 discovery of genetic evidence indicating that the majority of modern-day Jewish men of the priestly tribe (kohanim) are descendants of a single common male ancestor, consistent with the biblical high priest, Aaron. Researchers from universities in Italy, Estonia, Portugal, France, the US and Russia contributed to the important study, which was published on-line by the prestigious American Journal of Human Genetics on Thursday and will appear in print in the March. The Technion team's discoveries have significant implications beyond their inherent interest and relevance to human history; they are vital to understanding the mechanisms of genetic health and disease in human populations. The researchers' conclusions are based on detailed comparative analysis of DNA sequence variation in the mitochondrial DNA (mtDNA) region of the human genome. This type of DNA is transmitted to descendants solely by the mother. The researchers found that the mtDNA of some 3.5 million of the 8 million Ashkenazi Jews currently living throughout the world can be traced back to only four women carrying distinct mtDNA of a type virtually absent in other populations. Non-Ashkenazi Jews also carry low frequencies of these distinct mtDNA types, thus providing evidence of shared maternal ancestry of Ashkenazi and non-Ashkenazi Jews. This is consistent with previous findings based on studies of the Y-chromosome, pointing to a similar pattern of shared paternal ancestry of global Jewish populations, originating in the Middle East. The researchers concluded that the four founding mtDNA - likely of Middle Eastern origin - underwent a major overall expansion in Europe during the last millennium. The Ashkenazi Jewish population has often been studied by experts in human genetics because of the accumulation of some 20 recessive hereditary disorders that are concentrated in this population, the authors wrote. The human genome project for mapping human DNA sequence variation has not only made it possible to predict certain genetic diseases, but also the identification of family and genealogical relationships (shared ancestries) among individuals. The human genome includes some three billion chemical letters (known as nucleotides), which comprise the sequence of nucleic acids in DNA in almost every cell of the human body. Most of the human genome is diploid, meaning that it has genetic material representing both parents. However, the Y-chromosome carried only by males is haploid (without maternal input), as is mitochondrial DNA, which has no paternal input. Thus geneticists can learn about paternal ancestry from the Y chromosome and material ancestry from mtDNA. As a result, DNA sequence analysis of these two regions of the human genome are important tools in phylogenetics - the study of global populations through genetic analysis.