PT  - JOURNAL ARTICLE
AU  - Gholson J. Lyon
AU  - Jason O’Rawe
TI  - Clinical genetics of neurodevelopmental disorders
AID  - 10.1101/000687
DP  - 2013 Jan 01
TA  - bioRxiv
PG  - 000687
4099  - http://biorxiv.org/content/early/2013/11/18/000687.short
4100  - http://biorxiv.org/content/early/2013/11/18/000687.full
AB  - There are ∼6 billion nucleotides in every cell of the human body, and there are ∼25-100 trillion cells in each human body. Given somatic mosaicism, epigenetic changes and environmental differences, no two human beings are the same, particularly as there are only ∼7 billion people on the planet. One of the next great challenges for studying human genetics will be to acknowledge and embrace complexity3–13. Every human is unique, and the study of human disease phenotypes (and phenotypes in general) will be greatly enriched by moving from a deterministic to a more stochastic/probabilistic model14–19. The dichotomous distinction between ‘simple’ and ‘complex’ diseases is completely artificial, and we argue instead for a model that considers a spectrum of diseases that are variably manifesting in each person. The rapid adoption of whole genome sequencing (WGS) and the Internet-mediated networking of people promise to yield more insight into this century-old debate2,20–25. Comprehensive ancestry tracking and detailed family history data, when combined with WGS or at least cascade-carrier screening26, might eventually facilitate a degree of genetic prediction for some diseases in the context of their familial and ancestral etiologies. However, it is important to remain humble, as our current state of knowledge is not yet sufficient, and in principle, any number of nucleotides in the genome, if mutated or modified in a certain way and at a certain time and place, might influence some phenotype during embryogenesis or postnatal life9,27–44.