{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:32:08Z","timestamp":1786375928661,"version":"build-2736575974"},"reference-count":95,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1RF1AG060285"],"award-info":[{"award-number":["1RF1AG060285"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01ES034796"],"award-info":[{"award-number":["R01ES034796"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["K01MH133970"],"award-info":[{"award-number":["K01MH133970"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008227","name":"ARCS Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008227","id-type":"DOI","asserted-by":"publisher"}]},{"name":"John B. Lyon Memorial Scholarship Award"},{"name":"HHMI Gilliam Award"},{"name":"Emory Transgenic Mouse and Genomics Cores"},{"DOI":"10.13039\/100007623","name":"Emory University School of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007623","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Genomic copy number variations, such as the 22q11.2 microdeletion syndrome, cause pleiotropic disorders that affect diverse organ systems and disrupt neurodevelopment. Deletions of the 22q11.2 locus reduce the dosage of up to 46 protein coding genes, raising questions about the identity of haploinsufficient genes and their genetic interactions contributing to 22q11.2 phenotypes. Here, we dissect functional and molecular relationships between two genes encoded within the 22q11.2 locus: the mitochondrial ribosomal protein gene MRPL40 and the mitochondrial citrate transporter SLC25A1. We show that a MRPL40 null mutation disrupts mitochondrial translation, impairs respiration, and affects multiple components of the SLC25A1 interactome, including factors required for lipid metabolism, mitochondrial ribosome subunits, and the mitochondrial RNA processing machinery. In silico coessentiality network analysis revealed correlated and anticorrelated fitness interactions linking MRPL40 and SLC25A1 to mitochondrial translation, intermediate carbon metabolism, and interferon signaling. We determined that Mrpl40-null mutations are embryonic lethal in mice, but Mrpl40\u2212\/+ mice are viable and displayed embryonic cardiac development and adult behavioral phenotypes. Similarly, Slc25a1+\/\u2212 animals showed embryonic cardiac developmental defects but lacked the adult behavioral phenotypes observed in Mrpl40\u2212\/+ mice. Surprisingly, transheterozygotic Slc25a1+\/\u2212;Mrpl40\u2212\/+ mice suppressed or mitigated cardiac development, behavioral, and brain transcriptome phenotypes observed in single heterozygotic animals. These results reveal that MRPL40 and SLC25A1 are haploinsufficient genes within the 22q11.2 locus that genetically and biochemically interact to define tissue development and physiology. Our findings provide a framework for understanding the complexity and type of gene dosage interactions within the 22q11.2 deletion syndrome locus.<\/jats:p>","DOI":"10.1093\/hmg\/ddag073","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T13:42:21Z","timestamp":1785159741000},"source":"Crossref","is-referenced-by-count":0,"title":["Suppressive genetic interactions between haploinsufficient mitochondrial genes encoded in the 22q11.2 microdeletion locus define brain and cardiac phenotypes"],"prefix":"10.1093","volume":"35","author":[{"given":"Meghan","family":"Wynne","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Emory University , 615 Michael Street, Atlanta, GA 30322 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A","family":"Zlatic","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University , 615 Michael Street, Atlanta, GA 30322 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin S","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Emory University School of Medicine, and Children's Healthcare of Atlanta , 1750 Haygood Dr., Atlanta, GA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1768-7841","authenticated-orcid":false,"given":"Amanda","family":"Crocker","sequence":"additional","affiliation":[{"name":"Program in Neuroscience, Middlebury College , Bicentennial Way, Middlebury, VT 05753 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadassah","family":"Mendez-Vazquez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University , 615 Michael Street, Atlanta, GA 30322 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Liporace","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University , 615 Michael Street, Atlanta, GA 30322 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avanti","family":"Gokhale","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University , 615 Michael Street, Atlanta, GA 30322 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristy","family":"Tower-Gilchrist","sequence":"additional","affiliation":[{"name":"Nell Hodgson Woodruff School of Nursing. Emory University , 1520 Clifton Rd NE, Atlanta, GA 30322 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxine","family":"Robinette","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University , 615 Michael Street, Atlanta, GA 30322 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan H","family":"Purcell","sequence":"additional","affiliation":[{"name":"Fralin Biomedical Research Institute at Virginia Tech Carilion , 4 Riverside Circle, Roanoke, VA 24016 ,","place":["United States"]},{"name":"School of Neuroscience, Virginia Tech , 210 Drillfield Dr.Blacksburg, Blacksburg, VA 24061, \u00a0","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2622-0127","authenticated-orcid":false,"given":"Gary J","family":"Bassell","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University , 615 Michael Street, Atlanta, GA 30322 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University , 615 Michael Street, Atlanta, GA 30322 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer Q","family":"Kwong","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Emory University School of Medicine, and Children's Healthcare of Atlanta , 1750 Haygood Dr., Atlanta, GA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2114-5271","authenticated-orcid":false,"given":"Victor","family":"Faundez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University , 615 Michael Street, Atlanta, GA 30322 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"2026081011262947500_ref1","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.cell.2012.02.039","article-title":"CNVs: harbingers of a rare variant revolution in psychiatric genetics","volume":"148","author":"Malhotra","year":"2012","journal-title":"Cell"},{"key":"2026081011262947500_ref2","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1038\/s41380-023-02293-8","article-title":"Genomic findings in schizophrenia and their implications","volume":"28","author":"Owen","year":"2023","journal-title":"Mol Psychiatry"},{"key":"2026081011262947500_ref3","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.bj.2021.02.003","article-title":"DNA copy number variation: main characteristics, evolutionary significance, and pathological aspects","volume":"44","author":"Pos","year":"2021","journal-title":"Biomed 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gene and oculocutaneous albinism type 1 (OCA1): a model for understanding the molecular biology of melanin formation","volume":"13","author":"Oetting","year":"2000","journal-title":"Pigment Cell Res"},{"key":"2026081011262947500_ref42","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1093\/emboj\/17.12.3484","article-title":"Binary specification of nonsense codons by splicing and cytoplasmic translation","volume":"17","author":"Thermann","year":"1998","journal-title":"EMBO J"},{"key":"2026081011262947500_ref43","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1007\/s00246-019-02161-9","article-title":"Defects in trabecular development contribute to left ventricular noncompaction","volume":"40","author":"Choquet","year":"2019","journal-title":"Pediatr Cardiol"},{"key":"2026081011262947500_ref44","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1007\/s00246-018-1882-z","article-title":"Potential common pathogenic pathways for the left ventricular 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