By analyzing previously published three-dimensional chromatin interaction data, we found that in nuclei the 22q11.2 region could be physically juxtaposed to 6p21, where the HLA loci are located. Although this observation needs to be confirmed, it is consistent with previous reports that immunodeficiency is one of the key features of 22q11.2 DS [126, 127]. Interestingly, our pathway analysis of the differentially expressed genes also showed that immune response was among the most significant GO terms, after apoptosis and programmed cell death. However, as noted above, HLA proteins appear to have non-immune effects on synaptogenesis, which could also conceivably underlie potential functional associations between HLA and 22q11.2 DS [101–105].
