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<span>Medical Genetics and Ophthalmic Genomics Unit</span>
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<h2>About our work</h2>
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<p>The Medical Genetics and Ophthalmic Genomics (MGOG) Unit seeks to understand the mechanistic basis of human heritable ocular disorders, including those in children and adults with rare diseases and syndromes. Causal genetic variation explaining central vision loss in pediatric blinding disorders is poorly understood for two reasons. First, current clinical genetic testing strategies fail to provide a molecular diagnosis in a large proportion of patients. Our understanding of variant pathogenicity is limited both by the rare frequency of these disorders, preventing creation of large disease-specific population studies, and by a lack of knowledge of the consequences of variation in the noncoding genome. Second, there are no established model systems for diseases of the macula and fovea, two neural retina specializations specific to the high acuity vision present only in humans, certain primates, lizards, and birds. Given that the macula and fovea are morphologically and molecularly distinct tissues, this creates hurdles to pre-clinical studies for gene-directed and cellular replacement therapies.</p><p>Our investigations are in the following areas:</p><ul><li>Modeling novel associations of ocular syndromes: novel candidate human disease genes are validated in zebrafish, mouse, and in vitro using CRISPR/Cas9 gene editing and developmental, molecular, and cellular biology investigations to elucidate disease mechanisms. We are currently modeling several new human disease genes in animal and cellular models. Several examples are PNPLA6 (Hufnagel et al, Journal of Medical Genetics, 2015), encoding neuropathy target esterase, CSDE1 (Guo et al, Science Advances, 2019), encoding a cold-shock domain containing RNA-binding protein, and UBA2 (Schur, Yousaf, Liu etc al, Genetics in Medicine, 2021), encoding a protein critical in SUMOylation. We have shown that, in all three cases, loss-of-function variants cause unique and recognizable neurodevelopmental disorders in humans as well as animal models, such as zebrafish. Our group has also collaborated to define multiple additional new disease-gene associations, including <em>SLC25A46</em>, <em>SMO</em>, and <em>MYRF</em>. In total, we have participated in the delineation of more than 10 new human disease genes.</li><li>Functional genomics: Defining disease-associations in the noncoding genome and in eye tissues using functional genomics techniques. Using RNAseq, ATACseq, and Hi-C, along with single-cell sequencing technologies, we are mapping the active genome in human ocular cells derived from primary and induced pluripotent cell lines for variant prioritization from human sequencing data. These transcriptomic efforts contributed to public databases such as eyeIntegration (eyeintegration.nei.nih.gov) and plae (plae.nei.nih.gov). These information are then used to annotate human exome and genome data to further genetic discovery for the coding and noncoding genome.</li></ul><p><em><strong>No longer accepting new fellows/trainees.</strong></em></p>
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<h2>Medical Genetics and Ophthalmic Genomics Unit key staff</h2>
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<div class="js-view-dom-id-02a25fc4e9fa8d61b375f27097fd8b32e6c79dc5f6461d186288ea3fd1b284b1 lab-alumni">
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</div>
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</article>
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<div class="c-callout__content">
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<h2 class="c-callout__heading">Research at NEI</h2>
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<ul><li><a href="/research/research-labs-and-branches">Research Labs and Branches</a></li><li><a href="/research/research-labs-and-branches/we-are-nei-intramural">Principal Investigators</a></li><li><a href="/grants-and-training/training-nei">Training at NEI</a></li><li><a href="/about/news-and-events/news">Research News</a></li></ul>
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<p class="views-element-container c-last-updated" id="block-views-block-nei-last-updated-block-1"><strong>Actualización más reciente:</strong> 26 de noviembre de 2024</p>
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Building 10, Room 10N226<br>
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<br>
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Bethesda,
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Maryland
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20892
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