Recent research in the Laird Lab addresses the developmental biological process of cell-cell mosaicism. Epigenetic variation in Fragile X syndrome provides a model of such mosaicism, which can have important phenotypic consequences. For individuals with Fragile X syndrome, the proportion of cells with hypermethylated FMR1 alleles is highly correlated with decreases in IQ scores compared with parental IQs (Stöger et al., 1997) and see Human Disease.
Variation in X-chromosome inactivation patterns, long appreciated as a consequence of random X-inactivation occurring in a small number of embryonic cells (Nesbitt, 1971; Fialkow, 1973), has special importance for the penetrance of the cognitive phenotype in females with Fragile X syndrome. Extremes of X-inactivation patterns of identical twins is correlated with IQ differences of 50-60 points (Tuckerman, Webb, and Bundey, 1985).
Epigenetic mosaicism has not been studied as extensively in normal development as it has in human disease. Because the fidelity of epigenetic inheritance is considerably lower than the fidelity of genetic inheritance (Laird et al., 2004), it is reasonable to expect that variations in developmental patterns within the normal range may arise from epigenetic switching leading to cell mosaicism.
The Laird Lab has published in others areas of Developmental Biology.