Things to consider:
1. How cost-effective would it be to design and build a custom home? How will the dollars per square foot cost to build compare to the dollars per square foot average in the area? Will you receive any kind of family discount from the uncle and/or grandfather?
2. How radical will your custom home be and how will this affect resale value? It's all well and good to design and build something that you like outside the "cookie-cutter" models, but you may find it difficult to sell something if it is too weird.
3. Could you achieve similar result by purchasing a fixer-upper and doing custom renovations? In some situations, this can be much more cost-effective than a ground-up project.