Publications

New Publication from Sarah Tishkoff, PhD
A new study published in The American Journal of Human Genetics examines anthropometric, cardiovascular and metabolic traits in 2,124 individuals from diverse populations across sub-Saharan Africa. Researchers analyzed 27 traits and identified more than 100 genetic variants with significant associations, many of which are rare outside Africa. The findings underscore the importance of including genetically diverse African populations in genomic research and in the development of more broadly applicable genetic prediction tools.
Anthropometric and cardio-metabolic trait variation and genetic associations in sub-Saharan Africa. Hansen MEB, Hazra U, Kim M, Raj SM, Fan S, Beggs W, Mpoloka SW, Mokone GG, Nyambo T, Meskel DW, Belay G, Hirbo J, Ranciaro A, Lachance J, Tishkoff SA. Anthropometric and cardio-metabolic trait variation and genetic associations in sub-Saharan Africa. Am J Hum Genet. 2026 Sep 3;113(9):2001-2020.

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.
A global view of human centromere variation and evolution. Gao S, Oshima KK, Chuang SC, Loftus M, Potapova TA, Montanari A, Gordon DS, Yang Z, Human Genome Structural Variation Consortium, Human Pangenome Reference Consortium, Mao Y, Hsieh P, Gerton JL, Konkel MK, Ventura M, Logsdon GA. Nature (2026) Aug 5. doi: 10.1038/d41586-026-02327-5. Epub ahead of print.

New Publication from Bogdan Pasaniuc, PhD
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.
Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences. Mandla R, Shi Z, Hou K, Wang Y, Mies G, Aw AJ, Cullina S; Penn Medicine BioBank; Kenny E, Mathieson I, Atkinson EG, Martin AR, Pasaniuc B. Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences. Nat Commun. 2026 Aug 12;17(1):9677.

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.
Single-allele chromatin tracing reveals cytokine-dependent super-enhancer repositioning in CD4⁺ T cells. Jay A, Zhou Y, Yoon S, Abeje BN, Chandra A, Michieletto MF, Wald J, Henao-Mejia J, Raj A, Faryabi RB, Vahedi G. Single-allele chromatin tracing reveals cytokine-dependent super-enhancer repositioning in CD4⁺ T cells. Immunity. 2026 Sep 8;59(9):2483-2499.e10.

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.
Biallelic inactivating variants in the chromatin remodeler DMAP1 cause a syndromic neurodevelopmental disorder. Wang Q, Sobering AK, Tirrito C, Haghshenas S, Hjortshøj TD, Platzer K, Redler S, March ME, Matsuoka LS, Xi H, Zoodsma J, Chen Y, Mori M, Leung ML, Couque N, Verloes A, Pouzet A, Giesbertz NA, Simon ME, Yearwood AK, Assing DL, Hsieh TC, Li JM, Levy MA, Kerkhof J, McConkey H, Rzasa J, Lauzon-Young C, Sulaiman RA, Abdulwahab F, Shamseldin HE, Almontashiri NA, Afqi M, Vedanarayanan V, Guillen Sacoto MJ, Wentzensen IM, Damseh NS, Birnbaum R, van Ommeren B, Hopman SM, Zaki MS, Elmakkawy G, Afzal E, Kim J, Efthymiou S, Houlden H, Nusrat A, Toft M, Abdullah U, Iqbal Z, Terek S, Alkuraya FS, Bhoj EJ, Maroofian R, Sadikovic B, Hakonarson H, Song Y, Li D. J Clin Invest. 2026 Jun 11;136(15):e198229

New Publication fro Stuart Grant, PhD
Congratulations to the Grant Lab and collaborators on their new publication in Genome Research,“Cross-species variant-to-function analyses implicate MEIS1 in conferring sleep abnormalities and impaired cerebellar development.” Using a cross-species approach that combined human genetic data with functional studies in zebrafish, the team identified MEIS1 as a key regulator of sleep maintenance and cerebellar development. The findings provide important biological insight into how genetic variants associated with insomnia influence sleep behavior and demonstrate the power of vertebrate models for validating genes identified through human genome-wide association studies.
Cross-species variant-to-function analyses implicate MEIS1 in conferring sleep abnormalities and impaired cerebellar development. Zimmerman AJ, Almeraya Del Valle E, Pahl MC, Doldur-Balli F, Keenan BT, Liu PZ, Shetty ZY, Tsundupalli TR, Palermo J, Krishnan A, Pippin JA, Wells AD, Veatch OJ, Chesi A, Gehrman PR, Keene AC, Pack AI, Grant SFA. Cross-species variant-to-function analyses implicate MEIS1 in conferring sleep abnormalities and impa ired cerebellar development. Genome Res. 2026 Sep 1;36(9):1785-1799.

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.
Genome-wide analysis implicates inner ear development in Ménière disease.  Shi Z, Mandla R, Li J, Li X, Zhang Z, Xhen S, Lapinska S, Flynn-Carroll AO, Pasiniuc B, Epstein DJ, Mathieson I. Genome-wide analysis implicates inner ear development in Ménière disease. Am J Hum Genet. 2026 Jul 2;113(7):1509-1520.

Villification of the intestinal epithelium is driven by Foxl1 through activation of PDGFRα and BMPs.  Zhu G, Rozenberg G, Lahori D, Schug J, Tigue M, Cheng L, Batmanov K, Kaestner KH. Villification of the intestinal epithelium is driven by Foxl1 through activation of PDGFRα and BMPs. Nat Commun. 2026 Feb 24;17(1):3122.

Interbreeding between Neanderthals and modern humans was strongly sex biased. Platt A, Harris DN, Tishkoff SA. Interbreeding between Neanderthals and modern humans was strongly sex biased. Science. 2026 Feb 26;391(6788):922-925. 

Hotwired: How the hidden power of heat makes us stronger. Gifford B. (2026). In Hotwired: How the Hidden Power of Heat Makes Us Stronger, science journalist Bill Gifford highlights groundbreaking research by Penn geneticist  Yana Kamberov on the evolutionary genetics of human sweat glands, explaining how humans’ exceptional sweating capacity evolved as a key thermoregulatory adaptation and contributor to endurance and resilience.

AAV8 gene therapy and dietary insults together precipitate cholestatic liver disease in a mouse model of X-linked myotubular myopathy. Pannia E, Simonian R, Sabha N, Maani N, Zhu Y, Karolczak S, Raileanu V, Bottiglieri T, Andreoletti G, Edgar RD, MacParland SA, Mitina A, Cho CE, Lawlor MW, Coleman KE, Byrne BJ, Deshwar AR, Dowling JJ. AAV8 gene therapy and dietary insults together precipitate cholestatic liver disease in a mouse model of X-linked myotubular myopathy. Sci Transl Med. 2026 Feb 18;18(837):eadr1483.

GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density. Mitchell Conery, James A. Pippin, Yadav Wagley, Khanh Trang1, Matthew C. Pahl, David A. Villani, Lacey J. Favazzo, Cheryl L. Ackert‑Bicknell, Michael J. Zuscik, Eugene Katsevich, Andrew D. Wells, Babette S. Zemel, Benjamin F. Voight, Kurt D. Hankenson, Alessandra Chesi, and Struan F. A. Grant. Genome Biol 26, 331 (2025).

Complex genetic variation in nearly complete human genomes. Logsdon GA, Ebert P, Audano PA, Loftus M, Porubsky D, Ebler J, Yilmaz F, Hallast P, Prodanov T, Yoo D, Paisie CA, Harvey WT, Zhao X, Martino GV, Henglin M, Munson KM, Rabbani K, Chin CS, Gu B, Ashraf H, Scholz S, Austine-Orimoloye O, Balachandran P, Bonder MJ, Cheng H, Chong Z, Crabtree J, Gerstein M, Guethlein LA, Hasenfeld P, Hickey G, Hoekzema K, Hunt SE, Jensen M, Jiang Y, Koren S, Kwon Y, Li C, Li H, Li J, Norman PJ, Oshima KK, Paten B, Phillippy AM, Pollock NR, Rausch T, Rautiainen M, Song Y, Söylev A, Sulovari A, Surapaneni L, Tsapalou V, Zhou W, Zhou Y, Zhu Q, Zody MC, Mills RE, Devine SE, Shi X, Talkowski ME, Chaisson MJP, Dilthey AT, Konkel MK, Korbel JO, Lee C, Beck CR, Eichler EE, Marschall T.  Nature 2025 2025 Aug;644(8076):430-441.  

Exclusion-based exome sequencing in critically ill adults 18–40 years old has a 24% diagnostic rate and finds racial disparities in access to genetic testing. Jessica I. Gold, Colleen M. Kripke, Regeneron Genetics Center, Penn Medicine BioBank, Theodore G. Drivas. Am J Hum Genet. Aug 7; 112(8): 1792-1804. 

Lineage-resolved analysis of embryonic gene expression evolution in C. elegans and C. briggsae. Large CRL, Khanal R, Hillier L, Huynh C, Kubo C, Kim J, Waterston RH, Murray JI. Science. 2025 Jun 19;388(6753):eadu8249.

Characterization of non-coding variants associated with transcription-factor binding through ATAC-seq-defined footprint QTLs in liver. Dudek MF, Wenz BM, Brown CD, Voight BF, Almasy L, Grant SFA. Am J Hum Genet. 2025 Apr 10:S0002-9297(25)00140-5.

A lack of commensal microbiota influences the male reproductive tract intergenerationally in mice. Trigg NA, Zhou SK, Harris JC, Lamonica MN, Nelson MA, Silverman MA, Kambayashi T, Conine CC. Reproduction. 2025 Mar 4;169(4):e240204. 

Nuclear speckles regulate functional programs in cancer. Alexander KA, Yu R, Skuli N, Coffey NJ, Nguyen S, Faunce CL, Huang H, Dardani IP, Good AL, Lim J, Li CY, Biddle N, Joyce EF, Raj A, Lee D, Keith B, Simon MC, Berger SL. Nat Cell Biol. 2025 Feb;27(2):322-335.

 Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal. Song X, Xia Z, Martinez D, Xu B, Spritzer Z, Zhang Y, Nugent E, Ho Y, Terzic B, Zhou Z. Cell Rep Med. 2025 Feb 18;6(2):101926.

Insufficient evidence for natural selection associated with the Black Death. Barton AR, Santander CG, Skoglund P, Moltke I, Reich D, Mathieson I. Nature. 2025 Feb;638(8051):E19-E22.

 Polygenic burden of short tandem repeat expansions promotes risk for Alzheimer's disease. Guo MH, Lee WP, Vardarajan B, Schellenberg GD, Phillips-Cremins JE. Nat Commun. 2025 Jan 28;16(1):1126.

Risk factors affecting polygenic score performance across diverse cohorts. Hui D, Dudek S, Kiryluk K, Walunas TL, Kullo IJ, Wei WQ, Tiwari H, Peterson JF, Chung WK, Davis BH, Khan A, Kottyan LC, Limdi NA, Feng Q, Puckelwartz MJ, Weng C, Smith JL, Karlson EW; Regeneron Genetics Center; Penn Medicine BioBank; Jarvik GP, Ritchie MD. Elife. 2025 Jan 24;12:RP88149.

G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells. Bahl V, Rifkind R, Waite E, Hamdan Z, May CL, Manduchi E, Voight BF, Lee MYY, Tigue M, Manuto N, Glaser B, Avrahami D, Kaestner KH. Sci Transl Med. 2025 Jan;17(779):eadi6148.

 The Pax transcription factor EGL-38 links EGFR signaling to assembly of a cell type-specific apical extracellular matrix in the Caenorhabditis elegans vulva. Schmidt HF, Darwin CB, Sundaram MV. Dev Biol. 2025 Jan;517:265-277.

Bidirectional Risk Modulator and Modifier Variant of Dilated and Hypertrophic Cardiomyopathy in BAG3. Park J, Levin MG, Zhang D, Reza N, Mead JO, Carruth ED, Kelly MA, Winters A, Kripke CM, Judy RL, Damrauer SM, Owens AT, Bastarache L, Verma A, Kinnamon DD, Hershberger RE, Ritchie MD, Rader DJ. JAMA Cardiol. 2024 Dec 1;9(12):1124-1133.

FMRP regulates MFF translation to locally direct mitochondrial fission in neurons. Fenton AR, Peng R, Bond C, Hugelier S, Lakadamyali M, Chang YW, Holzbaur ELF, Jongens TA. Nat Cell Biol. 2024 Dec;26(12):2061-2074.

Multiple allelic configurations govern long-range Shh enhancer-promoter communication in the embryonic forebrain. Harke J, Lee JR, Nguyen SC, Arab A, Rakowiecki SM, Hugelier S, Paliou C, Rauseo A, Yunker R, Xu K, Yao Y, Lakadamyali M, Andrey G, Epstein DJ, Joyce EF. Mol Cell. 2024 Dec 19;84(24):4698-4710.e6.

 Clustering-independent estimation of cell abundances in bulk tissues using single-cell RNA-seq data. Aubin RG, Montelongo J, Hu R, Gunther E, Nicodemus P, Camara PG. Cell Rep Methods. 2024 Nov 18;4(11):100905.

Conserved autism-associated genes tune social feeding behavior in C. elegans. Cowen MH, Haskell D, Zoga K, Reddy KC, Chalasani SH, Hart MP. Nat Commun. 2024 Oct 28;15(1):9301.

 Contrasting and combining transcriptome complexity captured by short and long RNA sequencing reads. Han SW, Jewell S, Thomas-Tikhonenko A, Barash Y. Genome Res. 2024 Oct 29;34(10):1624-1635.

Pooled endogenous protein tagging and recruitment for systematic profiling of protein function. Serebrenik YV, Mani D, Maujean T, Burslem GM, Shalem O. Cell Genom. 2024 Oct 9;4(10):100651.

 Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory. Feierman ER, Louzon S, Prescott NA, Biaco T, Gao Q, Qiu Q, Choi K, Palozola KC, Voss AJ, Mehta SD, Quaye CN, Lynch KT, Fuccillo MV, Wu H, David Y, Korb E. Mol Cell. 2024 Aug 8;84(15):2822-2837.e11.

 Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects. Fabyanic EB, Hu P, Qiu Q, Berríos KN, Connolly DR, Wang T, Flournoy J, Zhou Z, Kohli RM, Wu H. Nat Biotechnol. 2024 Jun;42(6):960-974.

Modeling type 1 diabetes progression using machine learning and single-cell transcriptomic measurements in human islets. Patil AR, Schug J, Liu C, Lahori D, Descamps HC; Human Pancreas Analysis Consortium; Naji A, Kaestner KH, Faryabi RB, Vahedi G. Cell Rep Med. 2024 May 21;5(5):101535.

Integrative functional genomic analyses identify genetic variants influencing skin pigmentation in Africans. Feng Y, Xie N, Inoue F, Fan S, Saskin J, Zhang C, Zhang F, Hansen MEB, Nyambo T, Mpoloka SW, Mokone GG, Fokunang C, Belay G, Njamnshi AK, Marks MS, Oancea E, Ahituv N, Tishkoff SA. Nat Genet. 2024 Feb;56(2):258-272.

Unveiling recent and ongoing adaptive selection in human populations. Gao Z. PLoS Biol. 2024 Jan 18;22(1):e3002469.

Sweat gland development requires an eccrine dermal niche and couples two epidermal programs. Dingwall HL, Tomizawa RR, Aharoni A, Hu P, Qiu Q, Kokalari B, Martinez SM, Donahue JC, Aldea D, Mendoza M, Glass IA; Birth Defects Research Laboratory (BDRL); Wu H, Kamberov YG. Dev Cell. 2024 Jan 8;59(1):20-32.e6.