Ohnologs -paralogous gene pairs generated by whole genome duplication- are 
enriched for dosage sensitive genes, that is, genes that have a phenotype due to 
copy number changes. Dosage sensitive genes frequently occur in the same 
metabolic pathway and in physically interacting proteins. Accumulating evidence 
reveals that functionally related genes tend to co-localize in the 
three-dimensional (3D) arrangement of chromosomes. We query whether the spatial 
distribution of ohnologs has implications for their dosage balance. We analyzed 
the colocalization frequency of ohnologs based on chromatin interaction datasets 
of seven human cell lines and found that ohnolog pairs exhibit higher spatial 
proximity in 3D nuclear organization than other paralog pairs and than randomly 
chosen ohnologs in the genome. We also found that colocalized ohnologs are more 
resistant to copy number variations and more likely to be disease-associated 
genes, which indicates a stronger dosage balance in ohnologs with high spatial 
proximity. This phenomenon is further supported by the stronger similarity of 
gene co-expression and of gene ontology terms of colocalized ohnologs. In 
addition, for a large fraction of ohnologs, the spatial colocalization is 
conserved in mouse cells, suggestive of functional constraint on their 3D 
positioning in the nucleus.