Exploring Disrupted Gene Networks in Human 22q11.2 Microdeletion

Abstract

Several deletions are observed at the 22q11 locus and are responsible for 22q11.2 deletion syndrome (22q11DS), also known as DiGeorge syndrome, conotruncal anomaly face syndrome, or velocardiofacial syndrome. These microdeletions on human chromosome 22 range from 0.7 to 3 Mb. Many genes are affected by 22q11.2 deletion. However, despite the well-established clinical signs for the diagnosis of 22q11.2 deletion syndrome, the interactome background of 22q11.2 deletion syndrome is unknown. Here, we analyzed protein–protein interaction networks (PPIs) to assess the influences of 3 Mb 22q11.2 deletion on this network. We compared the general human PPI network against a network without 48 genes of the 3 Mb 22q11.2 locus in a homozygous condition: we compared topological metrics, enrichment of gene ontology terms, community assignments, and edge rewiring. The PPI networks revealed that this deletion affected the relevance of hundreds of nondeleted genes. Additionally, this 22q11.2 deletion induces intense rewiring of subnetworks, promoting an accumulation of proteins associated with DiGeorge clinical signs (CTCF, YY1, TFAP2A, PPARG, PAX6, RAX, and E2F3) in a single community (community 1). Therefore, we identified new genes that may be associated with the 22q11.2 deletion syndrome. Altogether, the systemic approaches used here yielded new insights into the 22q11.2 deletion syndrome.

Received: 21 February 2024 | Revised: 26 April 2024 | Accepted: 29 April 2024

Conflicts of Interest

The authors declare that they have no conflicts of interest to this work.

Data Availability Statement

The data that support the findings of this study are openly available in Figshare at https://figshare.com/s/3ba9c70ea933f19b238c, https://figshare.com/s/bd2d409096a90ba3a57c, https://figshare.com/s/4d4ea6783504fde27c44, and https://figshare.com/s/951db97a3f4ab4c4f977.