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Human papillomavirus type 16 long control region and E6 variants stratified by cervical disease stage.

Marongiu L, Godi A, Parry JV, Beddows S - Infect. Genet. Evol. (2014)

Bottom Line: Almost all samples (110/112; 98%) were assigned to the EUR lineage, one sample was classified as European-Asian (EAS) and another African (Afr1a).None of these sites, however, including the T350G non-synonymous (L83V) substitution in E6, alone or in combination, were found to be associated with cervical disease stage.Monitoring intra-lineage, site-specific variants, such as T350G, is unlikely to be of diagnostic value.

View Article: PubMed Central - PubMed

Affiliation: Virus Reference Department, Public Health England, London, UK.

No MeSH data available.


Related in: MedlinePlus

Site-specific intra-type sequence diversity. Variation within the 1178 bp fragment is estimated using Shannon entropy, wherein a value of zero reflects site-specific conservation and higher values indicate increasing degrees of site-specific variation. A level of 5% variation equates to an entropy score of ca. 0.2. Site-specific variations above this level are indicated by convention, numbered according to the reference HPV16 sequence, K02718. The boundaries of the LCR (red) and E6 (green) are indicated as are major elements within the LCR, including the E2 binding site (E2BS), and transcriptional elements NF1, YY1, TEF1, AP1 and OCT1.
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f0010: Site-specific intra-type sequence diversity. Variation within the 1178 bp fragment is estimated using Shannon entropy, wherein a value of zero reflects site-specific conservation and higher values indicate increasing degrees of site-specific variation. A level of 5% variation equates to an entropy score of ca. 0.2. Site-specific variations above this level are indicated by convention, numbered according to the reference HPV16 sequence, K02718. The boundaries of the LCR (red) and E6 (green) are indicated as are major elements within the LCR, including the E2 binding site (E2BS), and transcriptional elements NF1, YY1, TEF1, AP1 and OCT1.

Mentions: We next used Shannon entropy to estimate site-specific variation (Fig. 2) which highlighted seven sites of significant variation: five in the LCR (G7193T, A7316C, T7449C, T7495C and G7520) and two in the E6 gene (T109C and T350G). The distribution of these variant sites was not clearly associated with any potential sub-clustering of the EUR lineage (Fig. 1B), with few exceptions. For example, T7449C was overrepresented in South Asian sequences (65% of sequences; 95%CI 45–81%) compared to the average (18%; 95%CI 14–23%; n = 255) (p < 0.001) and the T350G was underrepresented in East Asian sequences (8%; 95%CI 2–38%) compared to the average (44%; 95%CI 38–51%) (p = 0.014). These differences aside, EUR LCR–E6 variant sequences from England could be found distributed throughout these potential EUR variant sub-clusters (Fig. 1B). There were many other variant sites within the LCR region (n = 48 sites; 0.9–3.6% of total sequences) and E6 gene (n = 8; 0.9–2.7%), as exemplified by entropy scores of <0.2 (Fig. 2), but with each represented by only a handful of sequences within the panel. The mean pairwise distance of EUR LCR–E6 sequences in this study based on a single European country (0.29%; 95%CI 0.13–0.45%; n = 110) was similar to the mean pairwise distance of the geographically dispersed EUR sequences (0.35%; 0.21–0.49%; n = 145; Fig. 1B) (Cornet et al., 2012). Both of these were considerably less diverse than the panel of background HPV16 sequences regardless of variant lineage (1.34%; 0.99–1.69%; n = 353) (Cornet et al., 2012).


Human papillomavirus type 16 long control region and E6 variants stratified by cervical disease stage.

Marongiu L, Godi A, Parry JV, Beddows S - Infect. Genet. Evol. (2014)

Site-specific intra-type sequence diversity. Variation within the 1178 bp fragment is estimated using Shannon entropy, wherein a value of zero reflects site-specific conservation and higher values indicate increasing degrees of site-specific variation. A level of 5% variation equates to an entropy score of ca. 0.2. Site-specific variations above this level are indicated by convention, numbered according to the reference HPV16 sequence, K02718. The boundaries of the LCR (red) and E6 (green) are indicated as are major elements within the LCR, including the E2 binding site (E2BS), and transcriptional elements NF1, YY1, TEF1, AP1 and OCT1.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150919&req=5

f0010: Site-specific intra-type sequence diversity. Variation within the 1178 bp fragment is estimated using Shannon entropy, wherein a value of zero reflects site-specific conservation and higher values indicate increasing degrees of site-specific variation. A level of 5% variation equates to an entropy score of ca. 0.2. Site-specific variations above this level are indicated by convention, numbered according to the reference HPV16 sequence, K02718. The boundaries of the LCR (red) and E6 (green) are indicated as are major elements within the LCR, including the E2 binding site (E2BS), and transcriptional elements NF1, YY1, TEF1, AP1 and OCT1.
Mentions: We next used Shannon entropy to estimate site-specific variation (Fig. 2) which highlighted seven sites of significant variation: five in the LCR (G7193T, A7316C, T7449C, T7495C and G7520) and two in the E6 gene (T109C and T350G). The distribution of these variant sites was not clearly associated with any potential sub-clustering of the EUR lineage (Fig. 1B), with few exceptions. For example, T7449C was overrepresented in South Asian sequences (65% of sequences; 95%CI 45–81%) compared to the average (18%; 95%CI 14–23%; n = 255) (p < 0.001) and the T350G was underrepresented in East Asian sequences (8%; 95%CI 2–38%) compared to the average (44%; 95%CI 38–51%) (p = 0.014). These differences aside, EUR LCR–E6 variant sequences from England could be found distributed throughout these potential EUR variant sub-clusters (Fig. 1B). There were many other variant sites within the LCR region (n = 48 sites; 0.9–3.6% of total sequences) and E6 gene (n = 8; 0.9–2.7%), as exemplified by entropy scores of <0.2 (Fig. 2), but with each represented by only a handful of sequences within the panel. The mean pairwise distance of EUR LCR–E6 sequences in this study based on a single European country (0.29%; 95%CI 0.13–0.45%; n = 110) was similar to the mean pairwise distance of the geographically dispersed EUR sequences (0.35%; 0.21–0.49%; n = 145; Fig. 1B) (Cornet et al., 2012). Both of these were considerably less diverse than the panel of background HPV16 sequences regardless of variant lineage (1.34%; 0.99–1.69%; n = 353) (Cornet et al., 2012).

Bottom Line: Almost all samples (110/112; 98%) were assigned to the EUR lineage, one sample was classified as European-Asian (EAS) and another African (Afr1a).None of these sites, however, including the T350G non-synonymous (L83V) substitution in E6, alone or in combination, were found to be associated with cervical disease stage.Monitoring intra-lineage, site-specific variants, such as T350G, is unlikely to be of diagnostic value.

View Article: PubMed Central - PubMed

Affiliation: Virus Reference Department, Public Health England, London, UK.

No MeSH data available.


Related in: MedlinePlus