Positions
- Assistant Professor
-
Molecular & Human Genetics
Baylor College of Medicine
Houston, Texas, United States
Addresses
- Adult Genetics Clinic (Clinic)
-
Baylor College of Medicine - McNair Campus
7200 Cambridge St
Houston, TX, 77030
United States
Phone: (713) 798-7764
jennifer.posey@bcm.edu
Certifications
- Board Certification
- American Board of Internal Medicine
- Board Certification
- American Board of Medical Genetics and Genomics
Honors & Awards
- Chao Physician-Scientist Award
- Ting Tsung and Wei Fong Chao Foundation
- (07/2016)
- BCM "That's the Way" Award
Professional Statement
As a physician-scientist and a medical and human geneticist, my ultimate goal is to be able to translate our understanding of the relationship between an individual’s genotype and phenotype into actionable and treatable information in the clinic. The first step toward this goal is the elucidation of the complex relationships between genotypes and human disease phenotypes. My research program is focused on the following three scientific inquiries, each of which will lead to a more precise understanding of these relationships:
1. What is the genetic etiology of Postural Orthostatic Tachycardia Syndrome (POTS), and to what extent do genetic heterogeneity and more complex modes of inheritance play a role in the clinical expression of POTS?
POTS represents one of many adolescent- or adult-onset conditions for which the molecular contribution – and genetic architecture – of disease is not well understood (Posey et al., 2016). Despite numerous examples of families with POTS following an autosomal dominant mode of inheritance, candidate disease genes have not been forthcoming, supporting the possibility that genetic heterogeneity, or perhaps more complex modes of inheritance, may play a role in the clinical expression of this condition. To address this possibility, we have built a cohort of individuals and families with POTS and other forms of autonomic dysfunction and are applying and analyzing genomic methods to identify the molecular etiologies of disease in these individuals.
2. How common are dual molecular diagnoses, and can we take advantage of structured phenotype data to predict which individuals with rare conditions are more likely to have two (or more) molecular diagnoses contributing to disease expression?
Dual or multiple, molecular diagnoses break from the ‘one-gene-one-disease’ paradigm, resulting in two or more independently segregating Mendelian conditions within an individual. Despite being long-recognized to occur in ‘rare’ cases, the true frequency of multiple molecular diagnoses has only more recently been described with the emergence of genome-wide techniques, such as array comparative genomic hybridization (aCGH) and ES, enabling a comprehensive identification of rare variation. In collaboration with the BG diagnostic laboratory and the BHCMG, we demonstrated that multiple molecular diagnoses are identified in at least 4.9% of individuals for whom ES is diagnostic (Posey, Harel, et al., 2017). We are now expanding this cohort and utilizing structured phenotype data to develop methods to predict which individuals may have multiple molecular diagnoses.
3. What are the roles of nuclear and mitochondrial genome variation in the expression of atypical forms of diabetes?
Diabetes has been broadly classified into type 1 diabetes (T1D) associated with auto-immune destruction of the pancreas, and type 2 diabetes (T2D) with adult-onset insulin resistance and/or impaired glucose tolerance. Despite these classifications, approximately 1-4% of individuals < 18 years with diabetes have a monogenic form that is clinically (phenotypically) distinct from T1D and T2D. As a member of the Rare and Atypical DIAbetes NeTwork (RADIANT) consortium, we are applying genomic methods to identify the molecular etiology of rare, monogenic forms of diabetes.
1. What is the genetic etiology of Postural Orthostatic Tachycardia Syndrome (POTS), and to what extent do genetic heterogeneity and more complex modes of inheritance play a role in the clinical expression of POTS?
POTS represents one of many adolescent- or adult-onset conditions for which the molecular contribution – and genetic architecture – of disease is not well understood (Posey et al., 2016). Despite numerous examples of families with POTS following an autosomal dominant mode of inheritance, candidate disease genes have not been forthcoming, supporting the possibility that genetic heterogeneity, or perhaps more complex modes of inheritance, may play a role in the clinical expression of this condition. To address this possibility, we have built a cohort of individuals and families with POTS and other forms of autonomic dysfunction and are applying and analyzing genomic methods to identify the molecular etiologies of disease in these individuals.
2. How common are dual molecular diagnoses, and can we take advantage of structured phenotype data to predict which individuals with rare conditions are more likely to have two (or more) molecular diagnoses contributing to disease expression?
Dual or multiple, molecular diagnoses break from the ‘one-gene-one-disease’ paradigm, resulting in two or more independently segregating Mendelian conditions within an individual. Despite being long-recognized to occur in ‘rare’ cases, the true frequency of multiple molecular diagnoses has only more recently been described with the emergence of genome-wide techniques, such as array comparative genomic hybridization (aCGH) and ES, enabling a comprehensive identification of rare variation. In collaboration with the BG diagnostic laboratory and the BHCMG, we demonstrated that multiple molecular diagnoses are identified in at least 4.9% of individuals for whom ES is diagnostic (Posey, Harel, et al., 2017). We are now expanding this cohort and utilizing structured phenotype data to develop methods to predict which individuals may have multiple molecular diagnoses.
3. What are the roles of nuclear and mitochondrial genome variation in the expression of atypical forms of diabetes?
Diabetes has been broadly classified into type 1 diabetes (T1D) associated with auto-immune destruction of the pancreas, and type 2 diabetes (T2D) with adult-onset insulin resistance and/or impaired glucose tolerance. Despite these classifications, approximately 1-4% of individuals < 18 years with diabetes have a monogenic form that is clinically (phenotypically) distinct from T1D and T2D. As a member of the Rare and Atypical DIAbetes NeTwork (RADIANT) consortium, we are applying genomic methods to identify the molecular etiology of rare, monogenic forms of diabetes.
Selected Publications
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Assia Batzir N, Posey JE, Song X, Akdemir ZC, Rosenfeld JA, Brown CW, Chen E, Holtrop SG, Mizerik E, Nieto Moreno M, Payne K, Raas-Rothschild A, Scott R, Vernon HJ, Zadeh N; Baylor-Hopkins Center for Mendelian Genomics, Lupski JR, Sutton VR. " Phenotypic expansion of POGZ-related intellectual disability syndrome (White-Sutton syndrome). " Am J Med Genet A. 2020 Jan ; 182 (1) : 38-52.
Pubmed PMID: 31782611. -
Assia Batzir N, Kishor Bhagwat P, Larson A, Coban Akdemir Z, (...); Baylor-Hopkins Center for Mendelian Genomics, Posey JE, Lupski JR, Beaudet AL, Wangler MF. " Recurrent arginine substitutions in the ACTG2 gene are the primary driver of disease burden and severity in visceral myopathy. " Hum Mutat.. 2020 Mar ; 41 (3) : 641-654.
Pubmed PMID: 31769566. -
Hansen AW, Murugan M, Li H, Khayat MM, Wang L, (...), Posey JE, Yang Y, Wangler MF, Eng CM, Sutton VR, Lupski JR, Boerwinkle E, Gibbs RA. " A Genocentric Approach to Discovery of Mendelian Disorders. " Am J Hum Genet.. 2019 Nov 7; 105 (5) : 974-986.
Pubmed PMID: 31668702. -
Herman I, Jolly A, Du H, Dawood M, Abdel-Salam GMH, (…), Posey JE, Lupski JR. " Quantitative dissection of multilocus pathogenic variation in an Egyptian infant with severe neurodevelopmental disorder resulting from multiple molecular diagnoses " Am J Med Genet A.. 2022 ; 188 : 735-750.
Pubmed PMID: 34816580.
Memberships
- American Society of Human Genetics
- American College of Physicians
- American College of Medical Genetics
Funding
-
Individual Genomic Analyses to Discover the Molecular Basis and Mechanisms Contributing to Adult-Onset Disease
#K08 HG008986 - Grant funding from National Human Genome Research Institute (NHGRI)
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