Genomics, Genetics and Epigenetics Laboratory
Research Areas
Genetic studies of Human Ocular Disorders
Ocular development is a complex process requiring carefully orchestrated differentiation of cells. Study of the genetic causes of pediatric/early onset conditions provides important insight into the mechanisms of normal development and disease. For affected families, identification of a genetic cause provides more accurate diagnosis and medical management.
Developmental Genomics Program
Many genes important in early development are active in many parts of the body. Disruption of one of these genes can cause multiple congenital anomaly (MCA) syndromes. The current diagnosis rate for exome sequencing in MCA syndromes varies from 15-50% in different settings, indicating that additional causes remain to be identified. Through analysis of samples from affected families as well as work in zebrafish and iPSC cell lines, we aim to expand understanding of known developmental genes and identify new genes important in early development.
Meet Our Team
Elena Semina, PhD
Marjorie and Joseph Heil Professor of Ophthalmology & Visual Sciences; Professor, Pediatrics; Professor, Cell Biology, Neurobiology and Anatomy
Isabelle Banke, BS
Clinical Research Coordinator II
Kailey Frank, BS
Research Technologist II
Megan Fischer
G2 Student
Justin Freestone
Graduate Student
Gary Gardner
Research Technologist I
Linda Reis, MS, LCGC
Program Manager; Adjunct Instructor
Maria R. Replogle, PhD
Research Scientist I
Sarah Seese, PhD
Research Scientist I
Elena A. Sorokina, MS
Research Scientist I
Samuel Thompson
Research Technologist III
Publications
Ferre-Fernández JJ, Reis LM, Semina EV. Displacement of distant regulatory elements of FOXC1 as a potential human disease mechanism. Hum Genomics. 2025 Mar 29;19(1):33. PMID: 40158102
Reis LM, Basel D, Bitoun P, Walton DS, Glaser T, Semina EV. Novel Intragenic and Genomic Variants Highlight the Phenotypic Variability in HCCS-Related Disease. Genes (Basel). 2024 Dec 20;15(12):1636. PMID: 39766903 PMCID: PMC11675438
Ceroni F, Cicekdal MB, Holt R, Sorokina E, Chassaing N, Clokie S, Naert T, Talbot LV, Muheisen S, Bax DA, Kesim Y, Kivuva EC, Vincent-Delorme C, Lienkamp SS, Plaisancié J, De Baere E, Calvas P, Vleminckx K, Semina EV, Ragge NK. Deletion upstream of MAB21L2 highlights the importance of evolutionarily conserved non-coding sequences for eye development. Nat Commun. 2024 Oct 26;15(1):9245. doi: 10.1038/s41467-024-53553-2. PMCID: PMC11511899
Reis LM, Zaidman GW, Thompson S, Muheisen S, Glaser T, Semina EV. Further Evidence for a Possible Role for ZHFX4 in Human Ocular Development and Disease. Am J Med Genet A. 2024 Oct 25:e63911. Online ahead of print. PMCID: PMC11821440
Reis LM, Seese SE, Costakos D, Semina EV. Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms. Prog Retin Eye Res. 2024 Sep;102:101288. Epub 2024 Aug 2. PMCID: PMC11392650
Replogle MR, Thompson S, Reis LM, Semina EV. A De Novo Noncoding RARB Variant Associated with Complex Microphthalmia Alters a Putative Regulatory Element Human Mutation. 2024;2024. PMCID: PMC11501074
Farris J, Khanna C, Smadbeck JB, Johnson SH, Bothun E, Kaplan T, Hoffman F, Polonis K, Oliver G, Reis LM, Semina EV, Rust L, Hoppman NL, Vasmatzis G, Marcou CA, Schimmenti LA, Klee EW. Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld-Rieger Syndrome. Am J Med Genet A. 2024 May;194(5):e63542. PMCID: PMC11003841
Untaroiu A, Reis LM, Higgins BP, Walesa A, Zacharias S, Nikezic D, Costakos DM, Carroll J, Semina EV. In Vivo Assessment of Retinal Phenotypes in Axenfeld-Rieger Syndrome. Invest Ophthalmol Vis Sci. 2024 Apr 01;65(4):20. PMCID: PMC11005067
Reis LM, Maheshwari M, Capasso J, Atilla H, Dudakova L, Thompson S, Zitano L, Lay-Son G, Lowry RB, Black J, Lee J, Shue A, Kremlikova Pourova R, Vaneckova M, Skalicka P, Jedlickova J, Trkova M, Williams B, Richard G, Bachman K, Seeley AH, Costakos D, Glaser TM, Levin AV, Liskova P, Murray JC, Semina EV. Axenfeld-Rieger syndrome: more than meets the eye. J Med Genet. 2023 Apr;60(4):368-379. PMCID: PMC9912354
Reis LM, Chassaing N, Bardakjian T, Thompson S, Schneider A, Semina EV. ARHGAP35 is a novel factor disrupted in human developmental eye phenotypes. Eur J Hum Genet. 2023 Mar;31(3):363-367. PMCID: PMC9995503
Daruich A, Duncan M, Robert MP, Lagali N, Semina EV, Aberdam D, Ferrari S, Romano V, des Roziers CB, Benkortebi R, De Vergnes N, Polak M, Chiambaretta F, Nischal KK, Behar-Cohen F, Valleix S, Bremond-Gignac D. Congenital aniridia beyond black eyes: From phenotype and novel genetic mechanisms to innovative therapeutic approaches. Prog Retin Eye Res. 2023 Jul;95:101133. PMCID: PMC11062406
Seese SE, Muheisen S, Gath N, Gross JM, Semina EV. Identification of HSPA8 as an interacting partner of MAB21L2 and an important factor in eye development. Dev Dyn. 2023 Apr;252(4):510-526. PMCID: PMC10947772
Reis LM, Atilla H, Kannu P, Schneider A, Thompson S, Bardakjian T, Semina EV. Distinct Roles of Histone Lysine Demethylases and Methyltransferases in Developmental Eye Disease. Genes (Basel). 2023 Jan 14;14(1). PMCID: PMC9859058
Oppermann H, Marcos-Grañeda E, Weiss LA, Gurnett CA, Jelsig AM, Vineke SH, Isidor B, Mercier S, Magnussen K, Zacher P, Hashim M, Pagnamenta AT, Race S, Srivastava S, Frazier Z, Maiwald R, Pergande M, Milani D, Rinelli M, Levy J, Krey I, Fontana P, Lonardo F, Riley S, Kretzer J, Rankin J, Reis LM, Semina EV, Reuter MS, Scherer SW, Iascone M, Weis D, Fagerberg CR, Brasch-Andersen C, Hansen LK, Kuechler A, Noble N, Gardham A, Tenney J, Rathore G, Beck-Woedl S, Haack TB, Pavlidou DC, Atallah I, Vodopiutz J, Janecke AR, Hsieh TC, Lesmann H, Klinkhammer H, Krawitz PM, Lemke JR, Jamra RA, Nieto M, Tümer Z, Platzer K. CUX1-related neurodevelopmental disorder: deep insights into phenotype-genotype spectrum and underlying pathology. Eur J Hum Genet. 2023 Nov;31(11):1251-1260. PMCID: PMC10620399
Amlie-Wolf L, Bardakjian T, Kopinsky SM, Reis LM, Semina EV, Schneider A. Review of 37 patients with SOX2 pathogenic variants collected by the Anophthalmia/ Microphthalmia Clinical Registry and DNA research study. Am J Med Genet A. 2022 Jan;188(1):187-198. PMCID: PMC9169870
Al-Jawahiri R, Foroutan A, Kerkhof J, McConkey H, Levy M, Haghshenas S, Rooney K, Turner J, Shears D, Holder M, Lefroy H, Castle B, Reis LM, Semina EV, University of Washington Centre for Mendelian Genomics (UW-CMG), Lachlan K, Chandler K, Wright T, Clayton-Smith J, Hug FP, Pitteloud N, Bartoloni L, Hoffjan S, Park SM, Thankamony A, Lees M, Wakeling E, Naik S, Hanker B, Girisha KM, Agolini E, Giuseppe Z, Alban Z, Tessarech M, Keren B, Afenjar A, Zweier C, Reis A, Smol T, Tsurusaki Y, Nobuhiko O, Sekiguchi F, Tsuchida N, Matsumoto N, Kou I, Yonezawa Y, Ikegawa S, Callewaert B, Freeth M, Genomics England Research Consortium, Kleinendorst L, Donaldson A, Alders M, De Paepe A, Sadikovic B, McNeill A. SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile. Genet Med. 2022 Jun;24(6):1261-1273. PMCID: PMC9245088
Reis LM, Seese S, Maheshwari M, Basel D, Weik L, McCarrier J, University Of Washington Center For Mendelian Genomics, Semina EV. Novel Genetic Diagnoses in Septo-Optic Dysplasia. Genes (Basel). 2022 Jun 28;13(7). PMCID: PMC9320703
Hijazi H, Reis LM, Pehlivan D, Bernstein JA, Muriello M, Syverson E, Bonner D, Estiar MA, Gan-Or Z, Rouleau GA, Lyulcheva E, Greenhalgh L, Tessarech M, Colin E, Guichet A, Bonneau D, van Jaarsveld RH, Lachmeijer AMA, Ruaud L, Levy J, Tabet AC, Ploski R, Rydzanicz M, Kępczyński Ł, Połatyńska K, Li Y, Fatih JM, Marafi D, Rosenfeld JA, Coban-Akdemir Z, Bi W, Gibbs RA, Hobson GM, Hunter JV, Carvalho CMB, Posey JE, Semina EV, Lupski JR. TCEAL1 loss-of-function results in an X-linked dominant neurodevelopmental syndrome and drives the neurological disease trait in Xq22.2 deletions. Am J Hum Genet. 2022 Dec 01;109(12):2270-2282. PMCID: PMC9748253
Reis LM, Sorokina EA, Dudakova L, Moravikova J, Skalicka P, Malinka F, Seese SE, Thompson S, Bardakjian T, Capasso J, Allen W, Glaser T, Levin AV, Schneider A, Khan A, Liskova P, Semina EV. Comprehensive phenotypic and functional analysis of dominant and recessive FOXE3 alleles in ocular developmental disorders. Hum Mol Genet. 2021 Aug 12;30(17):1591-1606. PMCID: PMC8369840
Seese SE, Reis LM, Deml B, Griffith C, Reich A, Jamieson RV, Semina EV. Identification of missense MAB21L1 variants in microphthalmia and aniridia. Hum Mutat. 2021 Jul;42(7):877-890. PMCID: PMC8238893
Seese SE, Deml B, Muheisen S, Sorokina E, Semina EV. Genetic disruption of zebrafish mab21l1 reveals a conserved role in eye development and affected pathways. Dev Dyn. 2021 Aug;250(8):1056-1073. PMCID: PMC8349561
Reis LM, Costakos D, Wheeler PG, Bardakjian T, Schneider A, Fung SSM, University of Washington Center for Mendelian Genomics, Semina EV. Dominant variants in PRR12 result in unilateral or bilateral complex microphthalmia. Clin Genet. 2021 Mar;99(3):437-442. PMCID: PMC8259391
Sorokina EA, Reis LM, Thompson S, Agre K, Babovic-Vuksanovic D, Ellingson MS, Hasadsri L, van Bever Y, Semina EV. WDR37 syndrome: identification of a distinct new cluster of disease-associated variants and functional analyses of mutant proteins. Hum Genet. 2021 Dec;140(12):1775-1789. PMCID: PMC9241141
Reis LM, Basel D, McCarrier J, Weinberg DV, Semina EV. Compound heterozygous splicing CDON variants result in isolated ocular coloboma. Clin Genet. 2020 Nov;98(5):486-492. PMCID: PMC8341436
Ferre-Fernández JJ, Sorokina EA, Thompson S, Collery RF, Nordquist E, Lincoln J, Semina EV. Disruption of foxc1 genes in zebrafish results in dosage-dependent phenotypes overlapping Axenfeld-Rieger syndrome. Hum Mol Genet. 2020 Sep 29;29(16):2723-2735. PMCID: PMC7530528
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Support the Genomics, Genetics, and Epigenetics (GGE) Laboratory
The GGE Laboratory could not exist without the generosity and support of federal agencies and individual donors. Funds donated to the program are used to acquire new equipment and research consumables, to provide clinically confirmed results back to participants, to enable the presentation of our research findings at scientific meetings and to fund positions for support staff. Please contact SeminaGenetics@mcw.edu with have any questions. If you are interested in supporting our program at any level please click below, select “Other” from the drop-down menu and indicate ‘Elena Semina’ to donate securely online.
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Join our studies
Enrollment in our studies is open to individuals affected with relevant conditions living in the United States or Canada. We are able to enroll in-person or remotely via a phone/Zoom call with samples collected at home.Genetic Studies of Human Ocular Disorders
Developmental Genomics Program
Feedback From Our Families
Having a confirmed diagnosis has been wonderful. I can say this is what my child has and this is how we can help him.
GGE Lab Study Participant
"Very appreciative to have been included. Also, very happy with the professionalism of the staff of researchers and the quick and personal responses"
GGE Lab Study Participant
"Relief. While the number of individuals identified with this syndrome is incredibly small, the characteristics or potential other issues are minimal. The nagging worry that something may be seriously wrong and just was not identified yet is gone."
GGE Lab Study Participant
"I am happy our genetic cause has been identified so now more families can be helped."
GGE Lab Study Participant
Contact Us
Genomics, Genetics, and Epigenetics (GGE) Laboratory
(414) 955-7645
seminagenetics@mcw.edu