Cystic fibrosis (and most rare genetic disorders) can be caused by multiple different genetic variants within a single gene. Because the effect of the genetic variants is so strong, cystic fibrosis follows an autosomal dominant inheritance pattern in families with the disorder. One of the major successes of human genetics was the identification of multiple mutations in the CFTR gene as the cause of cystic fibrosis [8]. This was achieved by genotyping families affected by cystic fibrosis using a collection of genetic markers across the genome, and examining how those genetic markers segregate with the disease across multiple families. This technique, called linkage analysis, was subsequently applied successfully to identify genetic variants that contribute to rare disorders like Huntington disease [9]. When applied to more common disorders, like heart disease or various forms of cancer, linkage analysis has not fared as well. This implies the genetic mechanisms that influence common disorders are different from those that cause rare disorders [10].
