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 driver mutations are enriched and associated with inflammatory states in Alzheimer's disease microglia

Huang AY*, Zhou Z*, Talukdar M*, Miller MB, Chhouk B, Enyenihi L, Rosen I, Stronge E, Zhao B, Kim D, Choi J, Khoshkhoo S, Kim J, Ganz J, Travaglini KJ, Gabitto M, Hodge RD, Kaplan E, Lein E, De Jager P, Bennett DA, Lee EA#, Walsh CA#. bioRxiv. 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


MosaicBase: A Knowledgebase of Postzygotic Mosaic Variants in Noncancer Diseases and Asymptomatic Human Individuals

Yang X*, Yang C*, Zheng X*, Xiong L, Tao Y, Wang M, Ye AY, Wu Q, Dou Y, Luo J, Wei L#, Huang AY#. Genom Proteom Bioinf. 2020


Somatic LINE-1 retrotransposition in cortical neurons and non-brain tissues of Rett patients and healthy individuals

Zhao B*, Wu Q, Ye AY, Guo J, Zheng X, Yang X, Yan L, Liu QR, Hyde TM, Wei L#, Huang AY#. PLoS Genet. 2019


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