Perspectives in Biology and Medicine

The first decades of the new medical genetics (1980 to 2000) were marked by resounding successes, with the identification of the genes responsible (when defective) for muscular dystrophy, cystic fibrosis, or Huntington’s disease, to name just a few of the several thousand Mendelian genetic conditions whose causes are now known. In contrast, the search for genes involved in common disorders such as diabetes, hypertension, schizophrenia, or autism failed miserably in the 1990s, with inconsistent and conflicting results—although the strong genetic component of these diseases (that also involve environmental factors) was (and still is) beyond doubt. From 2000 on, thanks to huge progress in genomic knowledge, technology, and analytical methods, it became possible to reliably identify genes influencing the risk of complex conditions, using the so-called GWAS (Genome-Wide Association Study) approach. Yet many problems remain, such as the vexing question of the “missing heritability,” or the difficulty of translating these scientific results into genetic tests with real clinical validity and utility. Autism is one of the cases in which a strong genetic component has been demonstrated, but where the search for causative genes remains difficult and attempts at developing valid genetic tests have failed, because of the many genes involved and possibly of the heterogeneity of the condition.