Coding single nucleotide substitutions (cSNSs) have been studied on hundreds of genes using small samples (ngapproximate to100-150 genes). In the present investigation, a large random European population sample (average ngapproximate to1500) was studied for a single gene, the CFTR ( Cystic Fibrosis Transmembrane conductance Regulator). The nonsynonymous (NS) substitutions exhibited, in accordance with previous reports, a mean probability of being polymorphic (q>0.005), much lower than that of the synonymous ( S) substitutions, but they showed a similar rate of subpolymorphic (q<0.005) variability. This indicates that, in autosomal genes that may have harmful recessive alleles (nonduplicated genes with important functions), genetic drift overwhelms selection in the subpolymorphic range of variability, making disadvantageous alleles behave as neutral. These results imply that the majority of the subpolymorphic nonsynonymous alleles of these genes are selectively negative or even pathogenic.

Modiano, G., Bombieri, C., Ciminelli, B.m., Belpinati, F., Giorgi, S., De_georges, M., et al. (2005). A large-scale study of the random variability of a coding sequence: a study on the CFTR gene. EUROPEAN JOURNAL OF HUMAN GENETICS, 13(2), 184-192 [10.1038/sj.ejhg.5201306].

A large-scale study of the random variability of a coding sequence: a study on the CFTR gene

MODIANO, GUIDO;CIMINELLI, BIANCA MARIA;
2005-01-01

Abstract

Coding single nucleotide substitutions (cSNSs) have been studied on hundreds of genes using small samples (ngapproximate to100-150 genes). In the present investigation, a large random European population sample (average ngapproximate to1500) was studied for a single gene, the CFTR ( Cystic Fibrosis Transmembrane conductance Regulator). The nonsynonymous (NS) substitutions exhibited, in accordance with previous reports, a mean probability of being polymorphic (q>0.005), much lower than that of the synonymous ( S) substitutions, but they showed a similar rate of subpolymorphic (q<0.005) variability. This indicates that, in autosomal genes that may have harmful recessive alleles (nonduplicated genes with important functions), genetic drift overwhelms selection in the subpolymorphic range of variability, making disadvantageous alleles behave as neutral. These results imply that the majority of the subpolymorphic nonsynonymous alleles of these genes are selectively negative or even pathogenic.
2005
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/18 - GENETICA
English
Con Impact Factor ISI
CFTR gene; Common vs rare alleles; Synonymous and nonsynonymous variability
Modiano, G., Bombieri, C., Ciminelli, B.m., Belpinati, F., Giorgi, S., De_georges, M., et al. (2005). A large-scale study of the random variability of a coding sequence: a study on the CFTR gene. EUROPEAN JOURNAL OF HUMAN GENETICS, 13(2), 184-192 [10.1038/sj.ejhg.5201306].
Modiano, G; Bombieri, C; Ciminelli, Bm; Belpinati, F; Giorgi, S; De_georges, M; Scotet, V; Pompei, F; Ciccacci, C; Guittard, C; Audrezet, Mp; Begnini,...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/27159
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