A method to map cellular lineage trees for humans. The human body is made of about 100 trillion cells, all of which are descendants of a single cell, the fertilized egg. The quest to understand their path of descent, called a cell lineage tree, is shared by many branches of biology. Cell lineage trees have been determined so far only for tiny organisms, relying on direct observations of developing embryos, a method which is inapplicable for humans, or even for newborn mice. Lineage relations among smaller subsets of cells are mainly studied using a variety of clonal assays. However, these assays provide limited lineage information because they determine only whether certain cells are descendants of the founder cell. Therefore, although there is a great need for a high-resolution method for cell lineage analysis, the current methods are very limited, with almost no possibility to study lineage relations in humans. The current technology consists of an automated procedure for the reconstruction of cell lineage trees for humans from DNA samples.
The outlined technology is based on the discovery that somatic mutations accumulated during normal development of a higher organism implicitly encode its entire cell lineage tree with very high precision. Mathematical analysis of known mutation rates in microsatellites (repetitive DNA elements) shows that the entire cell lineage tree of a human embryo, or a mouse, in which no cell is a descendent of more than 40 divisions, can be reconstructed from information on somatic microsatellites mutations alone with no errors, with probability greater than 99.95%.