Contribution of somatic mutation in human diseases

Somatic mutation, a previously overlooked genetic factor, can disrupt crucial gene function in carrier cells and contribute to the unexplained risk of human diseases. If a somatic mutation occurs in the germ cell lineage, it may be transmitted to the offspring, causing a de novo mutation. Our prior research discovered that somatic mutation plays a critical role in various diseases, including autism, Alzheimer's disease, and vascular malformation. We are currently deciphering the pathogenic contribution and mechanism of somatic mutations in many diseases, which will shed new light on their prevention, diagnosis, and treatment.

Related Publications

Somatic cancer variants enriched in Alzheimer disease microglia-like cells drive inflammatory and proliferative states

Huang AY*#, Zhou Z*, Talukdar M*, Enyenihi L*, Miller MB, Chhouk B, Rosen I, Zheng M, Zhou M, Yang A, Stronge E, Durens M, Nguyen M, Choi J, Zhao B, Khoshkhoo S, Kim J, Andersen R, An Z, Cheng Y, Ganz J, Mekerishvili L, Travaglini KJ, Gabitto MI, Hodge RD, Kaplan ES, Belk JA, Landau D, Lein ES, De Jager PL, Bennett DA, Marro SG#, Papapetrou EP#, Lee EA#, Walsh CA#. Cell. (Accepted)

Somatic Mosaicism in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Reveals Widespread Degeneration from Focal Mutations

Zhou Z*, Kim J*, Huang AY*, Nolan M, Park J, Doan R, Shin T, Miller MB, Bae M, Zhao B, Kim J, Chhouk B, Morillo K, Yeh RC, Kenny C, Neil JE, Lee C-Z, Ohkubo T, Ravits J, Ansorge O, Ostrow LW, Lagier-Tourenne C#, Lee EA#, Walsh CA#. Nat Genet. (Accepted)

Diverse somatic genomic alterations in single neurons in chronic traumatic encephalopathy

Dong G*, Ma CC*, Mao S, Brown KS, Naik SM, McDonough GA, Wijethunga SP, Kim J, Kirkham SL, Shao DD, Cherry JD, Uretsky M, Spurlock E, McKee AC, Huang AY#, Miller MB#, Lee EA#, Walsh CA#. Science. 2025

Analysis of DNA from brain tissue on stereo-EEG electrodes reveals mosaic epilepsy-related variants

D'Gama AM*, Phillips HW*, Wang Y*, Chiu MY, Chahine Y, Swanson AC, Smith RS, Pearl PL, Tsuboyama M, Madsen JR, Lidov H, Lee EA, Prabhu SP, Huang AY#, Stone SSD#, Walsh CA#, Poduri A#. Brain Commun. 2025

Neuropathologically directed profiling of PRNP somatic and germline variants in sporadic human prion disease

McDonough GA*, Cheng Y*, Morillo K, Doan RN, Kenny CJ, Foutz A, Kim C, Cohen ML, Appleby BS, Walsh CA, Safar JG, Huang AY#, Miller MB#. Acta Neuropathol. 2024

Somatic Mosaicism in PIK3CA Variant Correlates With Stereoelectroencephalography-Derived Electrophysiology

Phillips HW*, D'Gama AM*, Wang Y*, Chahine Y, Chiu M, Swanson AC, Ahtam B, Bolton JB, Madsen JR, Lee EA, Prabhu SP, Lidov HG, Papadakis J, Huang AY#, Poduri A#, Stone SS#, Walsh CA#. Neurol Genet. 2023

Somatic genomic changes in single Alzheimer’s disease neurons

Miller MB*, Huang AY*, Kim J, Zhou Z, Kirkham SL, Maury EA, Ziegenfuss JS, Reed HC, Neil JE, Rento L, Ryu SC, Ma CC, Luquette LJ, Ames HM, Oakley DH, Frosch MP, Hyman BT, Lodato MA#, Lee EA#, Walsh CA#. Nature. 2022

Somatic MAP2K1 Mutations Are Associated with Extracranial Arteriovenous Malformation

Couto JA*, Huang AY*, Konczyk DJ, Goss JA, Fishman SJ, Mulliken, JB, Warman ML, Greene AK#. Am J Hum Genet, 2017

Postzygotic single‐nucleotide mosaicisms contribute to the etiology of autism spectrum disorder and autistic traits and the origin of mutations

Dou Y*, Yang X, Li Z, Wang S, Zhang Z, Ye AY, Yan L, Yang C, Wu Q, Li J, Zhao B, Huang AY#, Wei L#. Hum Mutat. 2017