Most genetic disorders have been deliberately induced. There are some things that happen as a consequence of environmental degradation via radioactivity or chemical mutagens, but that is more recent due to the advent of human technological advancement to create many novel chemical substances and use them throughout the environment for pest control, and for preservation of foods, and in weaponry. There have been genetic alterations all through history designed to cause problems in human or done inadvertently with respect to actual outcome. There are many genetic alterations done to see what will happen as this can be a simpler way to sort out the actual workings of the genome. Those changes that are harmful but survivable, can persist through inheritance in many cases, and then add more problems to the overall gene pool.