The key idea is that genetic variants that have strong phenotypic effect through variation in just one gene are mostly rare, and genetic variants influencing most human traits of interest (heart disease risk, cancer risk, physical stature, alcoholism, IQ score, etc.) act in combination with many other gene variants, each of which alone has weak effect. This is the consistent finding of genome-wide association studies (GWASes) as those studies grow in sample size and in sophistication of the statistical analyses applied to them. Most gene variants in the human genome have nil effect on phenotype or such a weak effect that the influence of that one gene is undetectable even in GWASes with hundreds of thousands of subjects. So the word "rare" in the submitted article title (from the article description in the original article metadata) is the key word here.<p>These rare gene defects with strong effect on phenotype are likely to be helpful in illuminating the biological pathways involved in individuals developing those phenotypes, if the individuals are studied thoughtfully in clinical studies and especially if genetic engineering in an animal model can replicate the effect. But many of the diseases and disorders that you and I most care about will not be understood through this kind of research, because those diseases and disorders are already known to be polygenic (influenced by many genes, each of small effect) and multifactorial (subject to influence both from genes and from various environmental factors, some of which are very poorly understood). Identical (monozygotic) twins differ for many traits of interest, showing that influences other than genetic influences still make a difference in human development.