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Molecular and Human Genetics

Houston, Texas

Department of Molecular and Human Genetics
Department of Molecular and Human Genetics
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Christian Schaaf, M.D., Ph.D.

Christian Schaaf, M.D., Ph.D.Assistant Professor of Molecular and Human Genetics


M.D., University of Heidelberg, 2005
Ph.D., Human Genetics, University of Heidelberg, 2005
Resident, Clinical Genetics, Baylor College of Medicine, 2010

Research Interests

Our laboratory is dedicated to understanding the genetic basis of neurodevelopmental and neuropsychiatric disorders. Our research focuses on translating the understanding of the underlying cause into novel therapeutic strategies for some of these devastating conditions.

The alpha7 nicotinic receptor and neuropsychiatric disease: The CHRNA7 gene, which encodes the alpha7 nicotinic acetylcholine receptor, plays a prominent role in the etiology of neuropsychiatric disease (intellectual disability, epilepsy, autism, bipolar disorder, and others). We have collected a large cohort of families with CHRNA7 mutations (deletions, duplications, triplications, point mutations), and study their clinical, behavioral, and electrophysiological phenotypes. Translating our understanding of alpha7’s function in the central nervous system, and making use of cholinergic modulating drugs that are available, we investigate the use of cholinergic agonists in individuals with CHRNA7 deletion and cholinergic antagonists in CHRNA7 duplication carriers.

In the laboratory, we study the genetics of CHRNA7 and its chimeric fusion gene CHRFAM7A, which is a human-specific paralog that has arisen by segmental duplication during human evolution. Using molecular, biochemical, mouse genetic, and behavioral analyses, we investigate the role of CHRFAM7A, and its physical and functional interaction with CHRNA7.

The genetics of developmental regression: Among all individuals with intellectual disability, those who develop normally for several years, and then manifest profound developmental regression, are the most devastating and intriguing. While the genetic and molecular bases of intellectual disability and autism spectrum disorder continue to be discovered, very little is known about the etiology and pathogenesis of developmental regression. We study individuals with childhood disintegrative disorder, a form of autism that is characterized by profound regression, and have recently identified a novel gene that may account for a rare form this disorder. Using traditional molecular biology, large-scale proteomics, mouse genetics, and behavioral analyses, we investigate the function of the respective protein, and the pathophysiologic consequences of its loss of function.

We are interested in both bedside-to-bench and bench-to-bedside investigations. The former make use of the wealth of intriguing patients presenting to our medical genetics clinic, and the abundance of fascinating cases sent to the Molecular Genetics Laboratory. The latter is our attempt to translate molecular genetics and our growing understanding of the pathophysiology of disease back into the clinic, to ultimately benefit the affected patients and their families.

Selected Publications

  1. Schaaf CP, Gonzalez-Garay ML, Xia F, Potocki L, Gripp KW, Zhang B, Peters BA, McElwain MA, Drmanac R, Beaudet AL, Caskey CT, and Yang Y (2013). Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism. Nat. Genet., in press.
  2. Witsch J, Szafranski P, Chen CA, Immken L, Simpson Patel G, Hixson P, Cheung SW, Stankiewicz P, Schaaf CP. Intragenic deletions of the IGF1 receptor gene in five individuals with psychiatric phenotypes and developmental delay. Eur. J. Hum. Genet. 2013 Mar 13. [Epub ahead of print] PubMed PMID: 23486542
  3. Heil KM, Schaaf CP (2013). The genetics of Autism Spectrum Disorders--a guide for clinicians. Curr. Psychiatry Rep. 15(1): 334. PubMed PMID: 23250815
  4. Schaaf CP, Boone PM, Sampath S, Williams C, Bader PI, Mueller JM, Shchelochkov OA, Brown CW, Crawford HP, Phalen JA, Tartaglia NR, Evans P, Campbell WM, Tsai AC, Parsley L, Grayson SW, Scheuerle A, Luzzi CD, Thomas SK, Eng PA, Kang SH, Patel A, Stankiewicz P, Cheung SW (2012). Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions. Eur. J. Hum. Genet. 20(12): 1240-7. PubMed PMID: 22617343
  5. Schaaf CP, Wiszniewska J, Beaudet AL (2011). Copy number and SNP arrays in clinical diagnostics. Annu. Rev. Genomics Hum. Genet. 12: 25-51. PubMed PMID: 21801020
  6. Schaaf CP, Zoghbi HY (2011). Solving the autism puzzle a few pieces at a time. Neuron 70(5): 806-8. PubMed PMID: 21658575
  7. Schaaf CP, Sabo A, Sakai Y, Crosby J, Muzny D, Hawes A, Lewis L, Akbar H, Varghese R, Boerwinkle E, Gibbs RA, Zoghbi HY (2011). Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders. Hum. Mol. Genet. 20(17): 3366-75. PubMed PMID: 21624971
  8. Schaaf CP, Scott DA, Wiszniewska J, Beaudet AL (2011). Identification of incestuous parental relationships by SNP-based DNA microarrays. Lancet 377(9765): 555-6. PubMed PMID: 21315943
  9. Szafranski P, Schaaf CP, Person RE, Gibson IB, Xia Z, Mahadevan S, Wiszniewska J, Bacino CA, Lalani S, Potocki L, Kang SH, Patel A, Cheung SW, Probst FJ, Graham BH, Shinawi M, Beaudet AL, Stankiewicz P (2010). Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological? Hum. Mutat. 31(7): 840-50. PubMed PMID: 20506139
  10. Shinawi M, Schaaf CP, Bhatt SS, Xia Z, Patel A, Cheung SW, Lanpher B, Nagl S, Herding HS, Nevinny-Stickel C, Immken LL, Patel GS, German JR, Beaudet AL, Stankiewicz P (2009). A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes. Nat. Genet. 41(12): 1269-71. PubMed PMID: 19898479

Contact Information

Christian Schaaf, M.D., Ph.D.
Department of Molecular and Human Genetics, Baylor College of Medicine
The Jan and Dan Duncan Neurological Research Institute
1250 Moursund St, Suite 1325
Houston, TX, 77030, U.S.A.

Phone: 832-824-8787
Fax: 832-825-1251

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