Disease Example (nonallelic homologous recombination)

Hemophilia A is a coagulation disorder caused by mutation of the X chromosome gene F8, which codes for clotting factor VIII. Affected males have excessive bleeding of varying severity. Almost half of all severe hemophilia A results from an inversion mutation of exons 1-22 in F8, the underlying mechanism for which is abnormal pairing and recombination between two similar DNA sequences occurring in tandem.

Alpha thalassemia. The alpha globin genes on chromosome 16 are part of a highly homologous gene "family." The alpha globin cluster consists of five alpha-like genes, three functional and two pseudogenes, aligned head to tail along the chromosome. Because of the remarkable similarity between the genes, pseudogenes, and intron sequences in this cluster, homologous genes on chromosomes 16 can occasionally misalign at meiosis. This misalignment predisposes to unequal crossing over, thereby producing deletions and duplications.

Illustrations adapted from Nussbaum RL, McInnes RR, Willard HF, eds: Thompson & Thompson Genetics in Medicine, 6 ed. Genetic variation in individuals: mutation and polymorphism, Fig 6-2B (p 84) and Fig 3-7 (p 21). Copyright 2001, with permission from Elsevier.

Revised: 11-16-16

Related terms: deletion; duplication; gene conversion; recombination; unequal crossing over