Somatic Variation in Humans
Research type
Research Study
Full title
Investigating the contribution of somatic variation to development, differentiation and aging.
IRAS ID
158022
Contact name
Serena Nik-Zainal
Contact email
Research summary
Humans develop from a single fertlised egg, which undergoes mulitple rounds of cell division, during which cells acquire changes (somatic changes) to DNA. The changes can contribute to human diseases, and are likely to be different between cells of the same person, leading to inter-tissue variation, as well as between people.
For some genetic conditions, the same disease-causing mutation is not always expressed in all individuals who carry it i.e. not all carriers will show the disease phenotype (clinical symptoms). Moreover, when expressed, the mutation may not be expressed in the same way, leading to variation in the severity of symptoms experienced.
Somatic changes are one factor thought to contribute to the variability of disease phenotype, but our current knowledge on the causes remains limited.
Studying different cells or tissues from one individual and between individuals can help to provide insights into how acquired variation influences phenotypes. Using modern sequencing and modern cell-based approaches, we would like to exhaustively study cells/tissues from people who have genetic diseases as well as healthy people to better understand how and why humans develop so individually.
We envisage two broad approaches in our study:
First, we will acquire cells to derive induced pluripotent stem cells (iPSCs) and/or tissue samples (fresh/stored/surplus) from patients with known genetic diseases who have well-characterised clinical phenotypes (high-quality in vivo information), who have been appropriately consented. Second, we plan to supplement this work using modern gene-editing technologies to generate purely in vitro cell-based systems where we will systematically model variability between different cell-types.An identical set of experiments will also be carried out on healthy people in order to provide comparisons.
By studying somatic changes in patients suffering from genetic diseases, we hope to be better able to understand the clinical manifestations (symptoms) of individual disorders, which can often vary between sufferers.
REC name
East of England - Essex Research Ethics Committee
REC reference
14/EE/1061
Date of REC Opinion
22 Sep 2014
REC opinion
Further Information Favourable Opinion