Innovation
Research in the Department spans a broad spectrum of cutting-edge genetics, encompassing global genomics, evolution of complex traits, single-cell multiomics, precision gene editing, and mechanisms of epigenetic inheritance, among others.
Passion
Our faculty, trainees, and staff are united by an enduring curiosity about the fundamental principles of life and a relentless drive to uncover the genetic underpinnings of health and disease.
Collaboration
Scientific discovery in the Department is deeply collaborative by design. Faculty partner across disciplines with leading experts in medicine, computational biology, engineering, and public health to tackle the most complex questions in genetics.
Impact
Our labs combine advanced technologies with biological insights to accelerate the translation of genetic knowledge in precision medicine, enhance genomic diagnostics, and train future leaders in genomic science.
Message from the Chair: Daniel J. Rader, M.D.
Welcome to the Department of Genetics at the Perelman School of Medicine (PSOM) at the University of Pennsylvania. Our 35 primary faculty members conduct cutting-edge research across a broad spectrum of genetics and genomics, including human genetics, evolutionary and population genetics, epigenetics, functional genomics, experimental model systems, RNA biology, and computational and statistical genomics. Our research ranges from fundamental biological discovery to genomic medicine and translational therapeutics. As the central hub for genetics and genomics research on campus, the Department maintains strong collaborations with clinical departments and numerous Centers and Institutes across PSOM and the University. We also provide administrative oversight for several core facilities that support research laboratories throughout the School of Medicine and affiliated institutions. Additionally, the Department plays a vital role in educating medical and graduate students, as well as training the next generation of genomic scientists.
News
New Publication from Glennis Logsdon, PhD
A recent Nature study from the Logsdon lab provides the most comprehensive view to date of human centromere diversity and evolution by resolving and characterizing 2,110 centromeres from 65 individuals representing 28 global population groups. The study revealed extensive variation in centromere sequence, structure, and epigenetic organization, identifying 226 major centromere haplotypes and 1,870 α-satellite repeat variants. Kinetochore position was strongly associated with the underlying centromere sequence and structure, suggesting that genetic variation helps shape centromere chromatin organization. By extending these analyses to thousands of additional centromeres and a multigenerational family, the researchers further showed that centromeres evolve remarkably rapidly, with mutation rates varying more than 20-fold among chromosomes and the kinetochore-forming region representing the most rapidly changing portion of the centromere. Together, these findings reveal human centromeres as highly dynamic genomic regions and provide a framework for understanding how their rapid evolution may influence chromosome segregation and genome stability.
New publication from Bogdan Pasaniuc
In one of the largest admixture mapping study to date in African-European admixed individuals, researchers analyzed genetic and health data from nearly 49,000 participants in the NIH All of Us Research Program and Penn Medicine Biobank, identifying 71 ancestry-trait associations across 22 health-related traits. The study found little evidence of selection shaping genetic architecture of human traits since admixture while uncovering genetic associations that may be missed by traditional genome-wide association studies.
New Publication from Golnaz Vahedi, PhD
Researchers from Penn Genetics and their collaborators have shown how immune cells physically reorganize their genome to commit to a specialized fate. Naïve CD4⁺ T cells interpret cytokine cues to become helper T cells, a decision that requires reshaping how DNA folds inside the nucleus. Using single-allele chromatin tracing, a super-resolution imaging approach that follows individual chromatin fibers one cell at a time, the team studied the disease-associated Ets1–Fli1 locus. They found that cytokine signaling repositions a super-enhancer toward the geometric center of the folded locus, where it simultaneously engages the Ets1 and Fli1 genes and sustains the expression that T helper differentiation requires. Deleting the super-enhancer abolished this reorganization, leaving cells in a precursor-like state , offering a mechanistic framework for how noncoding variants at this locus may predispose individuals to immune-mediated disorders.
New Publication from Dong Li, PhD
Researchers from Penn Genetics and an international team of collaborators have identified DMAP1 as a new gene responsible for a syndromic neurodevelopmental disorder. Studying 20 patients from 16 families worldwide, the team found that biallelic variants in DMAP1, a protein involved in DNA methylation and chromatin remodeling, cause developmental delay, intellectual disability, seizures, hypotonia, and distinctive facial features. Using fruit flies to model the human variants, the researchers showed that DMAP1 is essential for brain development and identified two downstream target genes, Cbl and SF1, that may offer future therapeutic targets. The team also developed a DNA methylation "fingerprint" (episignature) that successfully diagnosed a previously unresolved patient, demonstrating a new tool for identifying this condition in the clinic.