@article{Bagnall01022005,
author = {Bagnall, Richard D. and Ayres, Karen L. and Green, Peter M. and Giannelli, Francesco}, 
title = {Gene conversion and evolution of Xq28 duplicons involved in recurring inversions causing severe hemophilia A},
volume = {15}, 
number = {2}, 
pages = {214-223}, 
year = {2005}, 
doi = {10.1101/gr.2946205}, 
abstract ={Inversions breaking the 1041 bp int1h-1 or the 9.5-kb int22h-1 sequence of the F8 gene cause hemophilia A in 1/30,000 males. These inversions are due to homologous recombination between the above sequences and their inverted copies on the same DNA molecule, respectively, int1h-2 and int22h-2 or int22h-3. We find that (1) int1h and int22h duplicated more than 25 million years ago; (2) the identity of the copies (>99%) of these sequences in humans and other primates is due to gene conversion; (3) gene conversion is most frequent in the internal regions of int22h; (4) breakpoints of int22h-related inversions also tend to involve the internal regions of int22h; (5) sequence variations in a sample of human X chromosomes defined eight haplotypes of int22h-1 and 27 of int22h-2 plus int22h-3; (6) the latter two sequences, which lie, respectively, 500 and 600 kb telomeric to int22h-1 are five-fold more identical when in cis than when in trans, thus suggesting that gene conversion may be predominantly intrachromosomal; (7) int1h, int22h, and flanking sequences evolved at a rate of about 0.1% substitutions per million years during the divergence between humans and other primates, except for int1h during the human-chimpanzee divergence, when its rate of evolution was significantly lower. This is reminiscent of the slower evolution of palindrome arms in the male specific regions of the Y chromosome and we propose, as an explanation, that intrachromosomal gene conversion and cosegregation of the duplicated regions favors retention of the ancestral sequence and thus reduces the evolution rate.}, 
URL = {http://genome.cshlp.org/content/15/2/214.abstract}, 
eprint = {http://genome.cshlp.org/content/15/2/214.full.pdf+html}, 
journal = {Genome Research} 
}