Small deletions and duplications frequently occur in the pericentromeric region 
of chromosomes and many of these are associated with developmental 
abnormalities. These developmental syndromes are conventionally attributed to 
abnormal expression of protein-coding genes in the affected region. A hypothesis 
has recently been published concerning a Master Development Program based on 
noncoding transcripts from these regions (Parris GE. A hypothetical Master 
Development Program for multi-cellular organisms: Ontogeny and phylogeny. Biosci 
Hypotheses 2009;2:3-12.). This paper summarizes and expands the recently 
published hypothesis to include it application to developmental diseases. The 
author proposes that development of multi-cellular organisms is guided by a 
Master Development Program (MDP) located primarily in the pericentromeric 
heterochromatin. The MDP is believed to consist of a series of 
Generation-Specific Control Keys (GSCK) transcribed in sequence by Ikaros family 
transcription factors unless the GSCKs are suppressed by Sall1-family or 
Dnmt3b-family proteins. The MDP is proposed to increment with each cell cycle to 
the next GSCK resulting in development of the clone. A clone may be programmed 
to split into two clones as necessary through a two-cycle mitosis processes. The 
transcripts of the GSCKs presumably yield noncoding nuclear messenger RNAs 
(nmRNAs, 8-30 nt units) that act directly (e.g., as primers for RNA polymerase 
II) and indirectly to regulate HOX and other high-level transcription factor and 
developmental genes. As envisioned, the MDP would evolve by terminal addition of 
new GSCKs. The new GSCKs are produced by evolutionary consolidation of 
retro-transcripts into pyknons that collect and evolve at the end of the 
pericentromeric heterochromatin and are eventually incorporated into the MDP. 
The retro-transcripts are though to be produced during episodic retrovirus 
epidemics and account for punctuated equilibrium in species evolution.