Epigenetics: We are more than just the sequence of our genes

Finding the missing heritability of complex diseases. Nature 461, 747-753(8 October 2009)

Ten years of genetics and genomics: what have we achieved and where are we heading?
Nat Rev Genet. 2010 Oct;11(10):723-33.
Heard E, et al.

Epigenetics provides hope that we are more than just the sequence of our genes–and our destiny and that of our children can be shaped, to some extent, by our lifestyle and environment.

… structural variants, such as highly repetitive DNA sequences, that may be inaccessible to the current high-throughput genotyping platforms.

One intriguing possibility is that a small portion of familial clustering is due to transgenerational effects— gene–environmental interaction events in parents, grandparents or beyond that alter the phenotypes and behaviors of the current generation.

debates rage on about ‘missing heritability’.

common alterations to gene expression and function do not map to obviously functional DNA changes, illustrating how little we know about genome function.

A recurrent theme emerging from such systematic, unbiased, high-throughput analyses is how much more complicated the molecular organization of the cell appears to be relative to what was originally revealed using focused, hypothesis-driven, reductionist molecular biology approaches.
Transcriptomes, both protein-coding and non-coding, are more complex than initially thought, by at least an order of magnitude, with more than 80% of the genome seemingly transcribed in humans.

estimates of the numbers of protein–protein and DNA–protein interactions that can happen in a single cell are in the range of 10exp5 to 10exp6.

The ‘gene number paradox’, according to which organisms of different complexity have similar numbers of protein-coding genes (for example, humans and worms both have approximately 20,000 genes)

Part of the confusion goes back to how we interchangeably use the concept of the gene as both a molecular encoding unit and a unit of heredity. but this classical problem has been enormously amplified in the past decade.
At the molecular level, it is increasingly harder to define the exact boundaries of both protein- and non-coding genes.
At the level of heredity, GWA studies now identify genes whose relative contribution to a particular phenotype of interest can be no more than a few per cent.

the kinds of genetic changes possible at any particular time in history and in each lineage depend on what kinds of transposable elements are present and active.

Estimating Trait Heritability