RNA

protein

DNAPromoter complexity – Transcriptional Start Sites,

Enhancers, Insulators, etc.

Structural variants:Deletions, Duplications & Inversions.

Physical variants (variation in receptors, etc).

Gene expressionmicroRNA

Epigenetics

Variation occurs at all levels of regulation in the system

SNPs & Haplotypes

Confers robustness and underlies

phenotypic diversity.

A stem cell model for neurological diseaseNasal biopsies from donors in a larger study on Parkinson's disease and Schizophrenia, and related controls.

Patient-Derived Cell Lines9 healthy (matched) controls

9 Schizophrenia patients13 Parkinson’s disease patients

• Stem cells isolated from olfactory neuroepithelium; are multipotent - giving rise to neurons and glia in culture.

• Patient-derived human olfactory neurosphere-derived (hONS) cells are informative and tissue-specific for studying the etiology of human brain disorders like SZ and PD.

Matigian et al. (2010) Disease Models & Mechanisms.

Control CellsAntibody-labeled Cells

Variance of gene expression identifies altered network constraints in neurological disease

Mar et al. (2011) PLoS Genetics.

Which genes have high variance across patients in the same disease group?

How is this distributed through the genome?

Difference in Averages

𝑻 (𝒈𝒆𝒏𝒆)=𝑫−𝑪

𝒇 (𝑽𝒂𝒓 (𝑫 ,𝑪 ))

𝑫 𝑪

Control Group

Disease Group

gene expression

𝑫 𝑪

Variance of gene expression identifies altered network constraints in neurological disease

Mar et al. (2011) PLoS Genetics.

Which genes have high variance across patients in the same disease group?

How is this distributed through the genome?