Two models accounting for origin of the double mutation in the amorph Rhnull disease gene. (A) Spontaneous mutation model. Sequences of codons 318-327 in RhD and RhCe genes are shown on top. Three mismatches at center right are marked by stars. Possible arrangements of the mutated region (boxed) in the amorph gene are depicted in two hypothetical schemes (see Discussion for details). a and b denote alternatives of the same scheme. Scheme I shows a noncontiguous deletion of two nucleotides, whereas scheme II shows a contiguous deletion of 2 nucleotides in association with a T→C transition. The BamHI site is shown. (B) Microgene conversion model. A heteroduplex is formed between RhD and RhCe genes via homologous pairing and strand synapsis. A failure in repair synthesis involving codons 322 and 323 would result in A→C transition and contiguous deletion of 2 nucleotides (boxed). This model is compatible with scheme II shown above but accommodates the latter in a single event.
