Multiple substitutions in the von Willebrand factor gene that mimic the pseudogene sequence.

Abstract

We have analyzed a type IIB and a type

A p47-phox pseudogene carries the most common mutation causing p47-phox- deficient chronic granulomatous disease.

“…As the products of crossing over and gene conversion events are virtually indistinguishable at the DNA level in higher eukaryotes, however, such events are commonly referred to as gene conversions (45). Gene conversion events between homologous genes and their pseudogenes have been described in the pathogenesis of several genetic disorders such as 21-hydroxylase deficiency (40), von Willebrand disease (46), and Gaucher disease (42), and have also been postulated for many clustered gene families (47). The presence of at least one p47-phox pseudogene carrying the GT deletion suggests that such events might also be responsible for the transfer of the GT deletion from the p47-phox pseudogene to the wild-type gene, thus leading to A47Њ CGD.…”

“…In addition, the HMR has been described as another hot spot for recombination in humans (37). The high incidence of recombination events between genes and pseudogenes for 21-hydroxylase or for von Willebrand factor has been attributed to the presence of Chi and HMR sequences in these genes (46,51,52). The presence of three Chi consensus sequences, one of them in intron 1, and one HMR consensus motif, might also be related to recombination events between p47-phox wild-type and pseudogene.…”

Pseudogenes in ribonuclease evolution: a source of new biomacromolecular function?

“…It is interesting to note that in the region of the kudu deletion, the sequence of the expressed seminal RNase gene in ox is quite similar to the sequence of the ox pancreatic gene, more than it is to the kudu seminal RNase pseudogene, and that this similarity extends some 70 base pairs into the 3'-untranslated region (with 62 of the 70 nucleobases, 89%, identical). We may speculate that information from the pancreatic gene may have been used to repair a damaged ancestral seminal RNase gene, perhaps by a gene conversion event [26][27][28][29]. This may be the first example of gene conversion being used to create new physiological function in paleogeological evolution, and it will be interesting to test this hypothesis with more sequence data.…”

T-cell clonality of undetermined significance

“…15 Six other cases of homologous gene conversion have been reported previously to be the cause of VWD type 1 or type 2B in 5 unrelated families. 15,16,17 A Q1311 mutation has also recently been detected in the homozygous state in 4 Spanish patients from 2 apparently unrelated families of gypsy origin. 18 The rest of the VWF gene was screened by investigating six overlapping mRNA segments.…”