Rheumatoid arthritis: Forward and reverse inheritance - the yin and the yang

Abstract

The theory of Mendelian inheritance states that half our genes are maternal and half are paternal. This view is incomplete, as maternal–fetal exchange creates a legacy of non-native cells within an individual that can affect their health for better or worse, including contributing to their risk of developing autoimmune disease.

Figure 1. Forward and reverse inheritance from microchimerism of maternal and of fetal origin

Maternal–fetal exchange creates a long-term legacy of a small number of cells in an individual that have a different genetic makeup, known as microchimerism. The individuals AC and EH in the middle generation harbour microchimerism from their mothers (AB and EF, respectively). In addition, AC can acquire cells from her children (AE, CH and AH) as a result of her own pregnancies. Other possible sources of microchimerism include a twin (including a vanished twin), pregnancies not resulting in a birth, and, potentially, previous microchimerism from maternal miscarriages or an older sibling that is carried with maternal cells to a later pregnancy (the latter illustrated as microchimerism from AE in AH).