Layered founders : a novel approach to investigate the ancestral transmission of complex traits

A novel approach based on graph theory is presented to reason about the genetic contribution of ancestors at different genealogical distances from today's individuals (different definitions of layers and distances are propos ed and discussed). It allows the maximum likelihood classification of specific founders who predominantly contribute to one class of individuals and the analysis of separability of specific founders with respect to two classes of individuals that have been selected based on LOD (logarithm of odds) score determined by a total genome scan and on ScaI marker genotype of a candidate gene of hypertension, ANP. Several experiments have been performed on a genealogy comprising more than 40,000 people and spanning 17 generations from the Saguenay-Lac-Saint-Jean population. We have computed: the founders obtained by using different definitions of layers and distances, the contribution of specific and unique founders, and the separability of specific founders. The results indicate that most defini tions of layers of founders show a similar trend over layers for size and content, that specific and unique genetic contributions are very high for recent generations and, as expected, decrease for older generations, and, also, that separability is higher for recent generations than for older ones. The presented approach allows a much finer grain analysis of genetic contribution of founders than previously-reported approaches.