Daryl Scott, M.D., Ph.D.
Assistant Professor of Molecular and Human Genetics
B.S., Brigham Young University, 1993
M.D./Ph.D., University of Iowa, 2000
Resident, Pediatrics, University of Utah, 2003
Resident, Clinical Genetics, Baylor College of Medicine, 2005
American Board of Pediatrics
American Board of Medical Genetics: Clinical Genetics
Member, American Society of Human Genetics
Member, American Academy of Pediatrics
Our laboratory is dedicated to identifying and characterizing genes that cause common, life-threatening birth defects and determining the molecular mechanisms by which they impact human health.
Congenital Diaphragmatic Hernia (CDH): Children with congenital diaphragmatic hernia (CDH) have an abnormal opening in the diaphragm that allows abdominal organs, like the liver and intestines, to enter into the chest. This invasion interferes with normal lung development causing severe respiratory problems at birth. CDH affects about one in every 2,500 newborns. To date, we have identified over 20 genomic regions that are recurrently deleted or duplicated in individuals with CDH. It is likely that each of these regions harbors one or more dosage-sensitive CDH genes. Using a combination of molecular cytogenetic data and mouse modeling, we have identified and characterized several genes that cause CDH in humans including HCCS, FZD2, FREM1 and ZFPM2. We have also developed novel mouse models for CDH that carry mutations in Sox7 and Frem1. We are now using these models to learn how diaphragmatic hernias form and how various CDH genes interact in vivo.
Esophageal Atresia/Tracheoesophageal Fistula (EA/TEF): Another life-threatening birth defect of interest is esophageal atresia/tracheoesophageal fistula (EA/TEF). During development, the esophagus (stomach tube) and the trachea (windpipe) develop from a common progenitor called the anterior foregut tube. In about one in 3,500 newborns, the development of these tubes is abnormal resulting in failure of the esophagus to reach the stomach (esophageal atresia) or an abnormal connection between the trachea and esophagus (tracheoesophageal fistula). Approximately 50% of EA/TEF cases occur in association with additional anomalies and 10% of cases have a constellation of findings known as VACTERL (Vertebral, Anal, Cardiac, TracheoEsophageal Fistula, Renal and Limb) association. We are presently using array-based copy number detection assays and whole exome sequencing to identify genes that cause these disorders.
1p36 Deletion Syndrome: Deletions of chromosome 1p36 can cause a variety of birth defects including brain anomalies, eye/vision problems, hearing loss, cardiovascular defects, cardiomyopathy and renal anomalies. Approximately one in 5,000 newborns carries either a terminal or interstitial deletion on chromosome 1p36. The RERE gene is located on chromosome 1p36 and encodes a nuclear receptor coregulator that plays an important role during embryonic development. Using mouse models developed in our laboratory, we have shown that RERE plays a critical role in the development of the brain, eye, inner ear, heart and kidneys. We are actively working to determine the molecular mechanisms by which RERE-deficiency causes defects in each of these organs.
- Beck TF, Veenma D, Shchelochkov OA, Yu Z, Kim BJ, Zaveri HP, van Bever Y, Choi S, Douben H, Bertin TK, Patel PI, Lee B, Tibboel D, de Klein A, Stockton DW, Justice MJ, Scott DA (2013). Deficiency of FRAS1-related extracellular matrix 1 (FREM1) causes congenital diaphragmatic hernia in humans and mice. Hum. Mol. Genet. 22(5): 1026-38. PubMed PMID: 23221805
- Kim BJ, Zaveri HP, Shchelochkov OA, Yu Z, Hernández-García A, Seymour ML, Oghalai JS, Pereira FA, Stockton DW, Justice MJ, Lee B, Scott DA (2013). An allelic series of mice reveals a role for RERE in the development of multiple organs affected in chromosome 1p36 deletions. PLoS One 8(2): e57460. PubMed PMID: 23451234
- Beck TF, Shchelochkov OA, Yu Z, Kim BJ, Hernández-García A, Zaveri HP, Bishop C, Overbeek PA, Stockton DW, Justice MJ, Scott DA (2013). Novel frem1-related mouse phenotypes and evidence of genetic interactions with gata4 and slit3. PLoS One 8(3): e58830. PubMed PMID: 23536828
- Wat MJ, Beck TF, Hernández-García A, Yu Z, Veenma D, Garcia M, Holder AM, Wat JJ, Chen Y, Mohila CA, Lally KP, Dickinson M, Tibboel D, de Klein A, Lee B, Scott DA (2012). Mouse model reveals the role of SOX7 in the development of congenital diaphragmatic hernia associated with recurrent deletions of 8p23.1. Hum. Mol. Genet. 21(18): 4115-25. PubMed PMID: 22723016
- Hernández-García A, Brosens E, Zaveri HP, de Jong EM, Yu Z, Namwanje M, Mayle A, Fernandes CJ, Lee B, Blazo M, Lalani SR, Tibboel D, de Klein A, Scott DA (2012). Contribution of LPP copy number and sequence changes to esophageal atresia, tracheoesophageal fistula, and VACTERL association. Am. J. Med. Genet. A 158A(7): 1785-7. PubMed PMID: 22639458
- Richards EG, Zaveri HP, Wolf VL, Kang SH, Scott DA (2011). Delineation of a less than 200 kb minimal deleted region for cardiac malformations on chromosome 7p22. Am. J. Med. Genet. A. 155(7): 1729-34. PubMed PMID: 21671376
- Wat MJ, Enciso VB, Wiszniewski W, Resnick T, Bader P, Roeder ER, Freedenberg D, Brown C, Stankiewicz P, Cheung SW, Scott DA (2010). Recurrent microdeletions of 15q25.2 are associated with increased risk of congenital diaphragmatic hernia, cognitive deficits and possibly Diamond-Blackfan anemia. J. Med. Genet. 47(11): 777-81. PubMed PMID: 20921022
- Qidwai K, Pearson DM, Patel GS, Pober BR, Immken LL, Cheung SW, Scott DA (2010). Deletions of Xp provide evidence for the role of holocytochrome C-type synthase (HCCS) in congenital diaphragmatic hernia. Am. J. Med. Genet. A. 152A(6): 1588-90. PubMed PMID: 20503342
- Wat MJ, Shchelochkov OA, Holder AM, Breman AM, Dagli A, Bacino C, Scaglia F, Zori RT, Cheung SW, Scott DA, Kang SH (2009). Chromosome 8p23.1 deletions as a cause of complex congenital heart defects and diaphragmatic hernia. Am. J. Med. Genet. A. 149A(8): 1661-77. PubMed PMID: 19606479
Awards and Honors
2000: National finalist for Council of Graduate Schools/UMI Outstanding Dissertation in the Biological and Life Sciences 1997-1999
1999: Spriestersbach Dissertation Prize, University of Iowa
1997: 3rd Place, Oral Presentation, Midwest Student Medical Research Forum
1996: Borts Award, University of Iowa Medical Student Research Day
1994: New Researcher Club Award, University of Iowa Medical Student Research Day
Daryl Scott, M.D., Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM227
Houston, TX, 77030, U.S.A.