Model of a possible crossover mechanism giving rise to the GTGT-containing ψNCF-1 and the prevalent A47°CGD allele.

In the top part of the figure, 2 chromosomes, each of the more common 2:1 extended haplotype, are misaligned. This event is probably most likely to occur between chromatids during meiosis. Dashed lines indicate possible sites of a double, reciprocal crossover event.NCF-1 is shown in green and its pseudogenes in red. The sequence at the start of exon 2 (GTGT or ΔGT) is shown above each gene, and the informative sequence differences (C/T in intron 1; 269G>A; 496A>G; 849A>G) are shown below (558A>G is omitted for the sake of clarity). The presence of the single (NCF-1) or duplicate (ψNCF-1) 20-bp stretch in intron 2 is indicated by bands in the body of the gene. The products of the crossover are shown in the bottom part of the figure, below the arrow. In the uppermost of these chromosomes, NCF-1 has acquired a pseudogene fragment containing ΔGT, resulting in the prevalent A47°CGD haplotype. One copy of ψNCF-1 on the lower chromosome has acquired a GTGT-containing fragment fromNCF-1 to form the Type II pseudogene (1:2 haplotype). In this model, the 3′ crossover site is based on data from subject P, but published data suggest that it is likely to vary. The exact position of the 5′ site is unknown, except that it is upstream of the C/T transition in intron 1 (see “Results and discussion”).