Somatic Mosaicism Across Human Tissues (SMaHT): Unlocking Genetic Diversity

The NIH has launched the SMaHT network, which will transform our understanding of biology and disease, with the potential to unlock new possibilities in genetics and medical research

Logo of the SMaHT project. Image provided by New York Genome Center

The National Institute of Health (NIH) Common Fund has launched a groundbreaking initiative: the SMaHT Network. The project has the potential to transform our understanding of somatic mosaicism in human cells and its influence on biology and disease. Though we typically think of our DNA as a fixed blueprint for life, recent research has revealed that genetic diversity can exist within a single individual. This phenomenon, known as somatic mosaicism, challenges our traditional understanding of genetics and can impact various fields from medicine to evolutionary biology.

Understanding Somatic Mosaicism

To comprehend SMaHT, it is important to first understand the concept of somatic mosaicism. Traditional genetics suggests that each individual carries a single, uniform set of genes throughout their body. However, somatic mosaicism demonstrates that genetic variation can occur within different tissues of the same individual.

Somatic mosaicism within humans refers to the presence of distinct genetic mutations or alterations in various tissues within the same person, or as defined by the Vaccarino Lab of the Yale School of Medicine, as “the accumulation of mutations in DNA sequence or copy number in cellular genomes after fertilization.” These mutations can encompass single nucleotide changes, structural alterations, or epigenetic modifications. As a result, each tissue in the body may possess its own unique genetic identity. The alterations in our DNA may lead to genetic variations among cells within our bodies.

While the scientific community recognizes somatic mosaicism's role in conditions like cancer and neurological disorders, the full extent of its role within our genomes and its overall influence on human biology remains a subject of ongoing study.

Project Goals

The SMaHT Network has several overarching goals:

1. The cataloging of somatic mosaicism to uncover the extent of somatic mosaicism in various cell types, disease states, and life stages, to give insights into how somatic mosaicism shapes fetal development, influences disease processes and leaves its mark on the aging human body.

2. Catalyzing research into the role of personal genomes in an array of diseases and disorders, from undiagnosed conditions to conditions affecting the skin, muscle, brain, and immune system.

3. Advancing sequencing technologies in order to achieve these goals, allows researchers to detect various forms of DNA variation, including rare mutations and reproductive cell variants, which would also provide more information into how both major and minor genetic variants contribute to biology and human development.

Outcomes and Innovations

The SMaHT Network envisions several outcomes and innovations:

1. Creation of a comprehensive catalog of the somatic variants found in diverse human donors' select tissues, which would serve as a foundation for deeper genetic exploration for many researchers worldwide.

2. Advancement of the sequencing tools and analysis methods used to detect genetic variants, which would benefit all researchers in the world of genetics.

3. Development of a data workbench that seamlessly integrates with current tools for DNA sequence analysis, such as genome browsers, which would fuse the analysis of somatic variation with the current human genome and provide a wider perspective of our genetic landscape.

4. Unlocking a new chapter and advancing genetic discovery, while also increasing our comprehension of somatic variation's contribution to human biology.

The SMaHT Network project is very promising, with the NIH allocating $140 million to support its endeavors. Many new insights are bound to be uncovered by researchers soon!