Implications of COMT long-range interactions on the phenotypic variability of 22q11.2 deletion syndrome.

[22q11.2 deletion syndrome]

22 q 11 .2 deletion syndrome (22 q 11 DS ) results from a hemizygous microdeletion on chromosome 22 and is characterized by extensive phenotypic variability . Penetrance of signs , including congenital heart , craniofacial , and neurobehavioral abnormalities , varies widely and is not well correlated with genotype . The three -dimensional structure of the genome may help explain some of this variability . The physical interaction profile of a given gene locus with other genetic elements , such as enhancers and co -regulated genes , contributes to its regulation . Thus , it is possible that regulatory interactions with elements outside the deletion region are disrupted in the disease state and modulate the resulting spectrum of symptoms . COMT , a gene within the commonly deleted ~3 Mb region has been implicated as a contributor to the neurological features frequently found in 22 q 11 DS patients . We used this locus as bait in a 4 C-seq experiment to investigate genome-wide interaction profiles in B lymphocyte and fibroblast cell lines derived from both 22 q 11 DS and unaffected individuals . All normal B lymphocyte lines displayed local , conserved chromatin looping interactions with regions that are lost in atypical and distal deletions , which may mediate similarities between typical , atypical , and distal 22 q 11 deletion phenotypes . There are also distinct clusterings of cis interactions based on disease state . We identified regions of differential trans interactions present in normal , and lost in deletion-carrying , B lymphocyte cell lines . This data suggests that hemizygous chromosomal deletions such as 22 q 11 DS can have widespread effects on chromatin organization , and may contribute to the inherent phenotypic variability .

Diseases
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Diseases presenting "extensive phenotypic variability" symptom

22q11.2 deletion syndrome

wolf-hirschhorn syndrome

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