D Haig offers the interesting suggestion that selective elimination of a recombinant CFTR gene TG12-T5-V470 haplotype would contribute to maintaining the different patterns of genetic variation seen on the M470 and the V470 haplotypes. He correctly indicates an increased frequency of the haplotype in CBAVD, and one might add in CF-like lung disease1 and nonclassic CF2 as well.
The effect of the selective elimination would be rather low though, as the haplotype would be eliminated only if: (1) it occurs in a male, and (2) it is compounded with a CF mutation (0.02). Therefore, the efficiency of transmission of this haplotype would be less than that of the other haplotypes, but just by 1%.
He suggests that a recombination process might have occurred between T5 and V470 on the CFTR gene: we would like to indicate that also a replication slippage mechanism might be involved in a change of nucleotide repeat number to generate the haplotype.
References
Noone PG, Pue CA, Zhou Z et al: Lung disease associated with the IVS8 5T allele of the CFTR gene. Am J Resp Crit Care Med 2000; 162: 1919–1924.
Groman JD, Hefferon TW, Casals T et al: Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign. Am J Hum Genet 2004; 74: 176–179.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pignatti, P. Reply to Professor Haig. Eur J Hum Genet 14, 801 (2006). https://doi.org/10.1038/sj.ejhg.5201621
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ejhg.5201621
