Figure 2

Maternal imprinting and mother male-feto microchimeristic genomic change. Proposed model of the segregation of susceptibility. Maternally imprinted susceptibility genes: Black square (affected male) or black circle (affected female); combined black and white (carrier); white (normal person) in four generations (I–IV). Mother-son microchimeristic changes of susceptibility genes: red capital “A to G” (strong expression of susceptibility); red small letters “a to g” (weak expression of susceptibility). Capital at the same line as the mother (acquired microchimeristic genomic change in the mother); red capital underlined (male inducer of microchimerism). Anticipation can be seen as an increased microchimeristic genomic load (red letters) down through the generations. Manifest disease depends on a certain load of susceptibility genes, for example black signature (imprinted genes) and at least two red letters (microchimeristic genomic changes). Paternal (PA) lines: Manifest male disease accumulates e.g. in the father-son line to the left in the figure from IIIAB to IVABD and further on in the PA males in the next generations with highly expressed microchimeristic genomic changes (red capitals only). And in the PA lines of sons of carrier fathers, e.g. IVaCF and further down in the next generations, all with partial expression of the microchimeristic genomic changes (mixed red capital and red small letters). Thus, the male probands in PA lines have a greater number of male affected relatives than female probands, because the female probands create carriers that break up the continuous lines of affected males and thereby reduce the number of available affected relative males per female proband. Maternal (MA) lines: An equal number of carrier males and females are produced from affected females. Transgenerational lines of female carriers are produced in MA lines, e.g. to the right in the figure from IIIacG to IVacg and further on in the subsequent generations of MA.