ABSTRACT
This chapter looks at the consequences of the exon-intron structure, both good and bad, starting with a famous case of an inherited bleeding disorder. Exons and introns have very different length distributions, as introns are typically much longer than the exons. The chapter considers a disorder that is the most common cause of inherited deafblindness. In the search for causative mutations in monogenic disorders, it is essential to take into the account any mutations with potential phenotypic consequences. Genomic variants in noncoding regions that affect splicing play a role in complex traits and disorders, as shown by analysis of human genomes. In the case a novel nonsynonymous mutation is identified in a coding region in the context of disorder, it is often thought to be causative, as many inherited disorders are the result of alterations in the amino acid sequence.
