Somatic mutation in normal development and aging

The accumulation of somatic mutations throughout development and aging is shaped by a variety of mutational processes, resulting in distinctive profiles of genomic contexts, known as “mutational signatures.” These mutations create inter-cellular genomic diversity and can serve as endogenous molecular barcodes for tracing developmental lineage. By utilizing state-of-the-art bulk and single-cell sequencing technologies, our team is investigating the mechanisms underlying somatic mutation accumulation in various human tissues, as well as their functional impacts on the transcriptome and epigenome of carrier cells.

Related Publications

Somatic mutations in single human cardiomyocytes reveal a rapid increase in age-associated DNA damage and widespread oxidative genotoxicity

Choudhury S*#, Huang AY*, Kim J, Zhou Z, Morillo K, Maury EA, Tsai JW, Miller MB, Lodato MA,  Araten S, Hilal N, Lee EA#, Chen MH#, Walsh CA#. Nat Aging. 2022

Parallel RNA and DNA analysis after Deep-sequencing (PRDD-seq) reveals cell type-specific lineage patterns in human brain

Huang AY*, Li P*, Rodin RE, Kim SN, Dou Y, Kenny CJ, Akula SK, Hodge RD, Bakken TE, Miller JA, Lein ES, Park PJ, Lee EA, Walsh CA#. PNAS. 2020

A model for postzygotic mosaicisms quantifies the allele fraction drift, mutation rate, and contribution to de novo mutations

Ye AY*, Dou Y*, Yang X, Wang S, Huang AY#, Wei L#. Genome Res. 2018

Distinctive types of postzygotic single-nucleotide mosaicisms in healthy individuals revealed by genome-wide profiling of multiple organs

Huang AY*#, Yang X*, Wang S, Zheng X, Wu Q, Ye AY, Wei L#. PLoS Genet. 2018