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PubMed1992

Molecular analysis of genetic mutation in electrophoretic variant of human lactate dehydrogenase-A(M) subunit.

An electrophoretic variant of lactate dehydrogenase-A (M) subunit was discovered in a patient with multiple myeloma. DNA analysis of the variant allele revealed a nucleotide substitution (transition) of C to T at codon 314 (CGT-TGT), and this mutation resulted in the replacement of an arginine by a cysteine (R314C). This amino acid replacement affects the net charge of the subunit and makes the LDH-A variant have a faster electrophoretic mobility. The responsible missense mutation created a new restriction site, AGGCCT, which can be simply detected by endonuclease AatI digestion. In addition, four synonymous substitutions with no amino-acid replacements were found at codons 51, 119, 163 and 175 in the LDH-A gene from the patient.

Aged↗
PubMed2005

Association of DRD2 gene variant with schizophrenia.

Schizophrenia is a complex multifactorial disorder for which the pathobiology still remains elusive. Dysfunction of the dopamine D2 receptor signaling has been associated with the illness, but numerous studies provide confounding results. This study investigates the association of synonymous polymorphisms (His313 and Pro319) in the dopamine D2 receptor gene with schizophrenia using a case-control approach, with 101 cases and 145 controls. Our results demonstrated that genotype distribution for the His313 polymorphism was significantly different between schizophrenia patients and control subjects (p=0.0012), while the Pro319 polymorphism did not show any association with the disease. The results suggest that the synonymous SNP His313 in DRD2 may be associated with the illness. However, there is a need for further replication studies with larger sample sets.

Adolescent↗
PubMed2003

Rates of DNA sequence evolution in experimental populations of Escherichia coli during 20,000 generations.

We examined rates of DNA sequence evolution in 12 populations of Escherichia coli propagated in a glucose minimal medium for 20,000 generations. Previous work saw mutations mediated by mobile elements in these populations, but the extent of other genomic changes was not investigated. Four of the populations evolved defects in DNA repair and became mutators. Some 500 bp was sequenced in each of 36 genes for 50 clones, including 2 ancestral variants, 2 clones from each population at generation 10,000, and 2 from each at generation 20,000. Ten mutations were found in total, all point mutations including mostly synonymous substitutions and nonsynonymous polymorphisms; all 10 were found in mutator populations. We compared the observed sequence evolution to predictions based on different scenarios. The number of synonymous substitutions is lower than predicted from measured mutation rates in E. coli, but the number is higher than rates based on comparing E. coli and Salmonella genomes. Extrapolating to the entire genome, these data predict about 250 synonymous substitutions on average per mutator population, but only about 3 synonymous substitutions per nonmutator population, during 20,000 generations. These data illustrate the challenge of finding sequence variation among bacterial isolates that share such a recent ancestor. However, this limited variation also provides a useful baseline for research aimed at finding the beneficial substitutions in these populations.

DNA, Bacterial↗
PubMed2005

Polymorphisms in the leptin receptor (LEPR)--putative association with obesity and T2DM.

Leptin plays an important role in regulating adipose-tissue mass. Leptin controls energy balance and food intake through the leptin receptor in the hypothalamus of the brain, which suggests that some polymorphisms of the leptin receptor gene (LEPR) might contribute to obesity or obesity-related diseases. In an effort to identify genetic polymorphisms in a potential candidate gene for obesity and type 2 diabetes mellitus (T2DM) in the Korean population, we have sequenced the LEPR gene. Thirty-five sequence variants were identified (including 9 novel polymorphisms): 1 single nucleotide polymorphism (SNP) in the promoter region, 1 SNP in the 5' UTR, 8 SNPs in exons (3 non-synonymous SNPs), 23 SNPs in introns, 1 ins/del in the 3' UTR, and 1 SNP in the 3' downstream region. To investigate possible association of LEPR polymorphisms with body mass index (BMI) and the risk of T2DM, we genotyped for 11 polymorphisms in the Korean population (n = 1,463). Using statistical analyses, no significant associations between the genetic polymorphisms in the LEPR gene and the risk of T2DM were detected. However, one non-synonymous SNP in exon 3, +5193G > A (Arg109Lys), showed marginal association with BMI (P = 0.02) and gene dose-dependent genetic effects were observed. The present study provides information about additional genetic polymorphisms in LEPR and positive associations of those polymorphisms with BMI in the Korean population.

Aged↗
PubMed2005

From DNA to fitness differences: sequences and structures of adaptive variants of Colias phosphoglucose isomerase (PGI).

Colias eurytheme butterflies display extensive allozyme polymorphism in the enzyme phosphoglucose isomerase (PGI). Earlier studies on biochemical and fitness effects of these genotypes found evidence of strong natural selection maintaining this polymorphism in the wild. Here we analyze the molecular features of this polymorphism by sequencing multiple alleles and modeling their structures. PGI is a dimer with rotational symmetry. Each monomer provides a critical residue to the other monomer's catalytic center. Sequenced alleles differ at multiple amino acid positions, including cryptic charge-neutral variation, but most consistent differences among the electromorph alleles are at the charge-changing amino acid sites. Principal candidate sites of selection, identified by structural and functional analyses and by their variants' population frequencies, occur in interpenetrating loops across the interface between monomers, where they may alter subunit interactions and catalytic center geometry. Comparison to a second (and basal) species, Colias meadii, also polymorphic for PGI under natural selection, reveals one fixed amino acid difference between their PGIs, which is located in the interpenetrating loop and accompanies functional differences among their variants. We also study nucleotide variability among the PGI alleles, comparing these data to similar data from another glycolytic enzyme gene, glyceraldehyde-3-phosphate dehydrogenase. Despite extensive nonsynonymous and synonymous polymorphism at PGI in each species, the only base changes fixed between species are the two causing the amino acid replacement; this absence of synonymous fixation yields a significant McDonald-Kreitman test. Analyses of these data suggest historical population expansion. Positive peaks of Tajima's D statistic, representing regions of neutral "hitchhiking," are found around the principal candidate sites of selection. This study provides novel views of molecular-structural mechanisms, and beginnings of historical evidence, for a long-persistent balanced enzyme polymorphism at PGI in these and perhaps other species.

Alleles↗
PubMed2024

Genetic evidence for predisposition to acute leukemias due to a missense mutation (p.Ser518Arg) in ZAP70 kinase: a case-control study.

BACKGROUND: The apparent lack of additional missense mutations data on mixed-phenotype leukemia is noteworthy. Single amino acid substitution by these non-synonymous single nucleotide variations can be related to many pathological conditions and may influence susceptibility to disease. This case-control study aimed to unravel whether the ZAP70 missense variant (rs104893674 (C > A)) underpinning mixed-phenotype leukemia. METHODS: The rs104893674 was genotyped in clients who were mixed-phenotype acute leukemia-, acute lymphoblastic leukemia- and acute myeloid leukemia-positive and matched healthy controls, which have been referred to all major urban hospitals from multiple provinces of country- wide, IRAN, from February 11' 2019 to June 10' 2023, by amplification refractory mutation system-polymerase chain reaction method. Direct sequencing for rs104893674 of the ZAP70 gene was performed in a 3130 Genetic Analyzer. RESULTS: We found that the AC genotype of individuals with A allele at this polymorphic site (heterozygous variant-type) contribute to the genetic susceptibility to acute leukemia of both forms, acute myeloid leukemia and acute lymphoblastic leukemia as well as with a mixed phenotype. In other words, the ZAP70 missense variant (rs104893674 (C > A)) increases susceptibility of distinct cell populations of different (myeloid and lymphoid) lineages to exhibiting cancer phenotype. The results were all consistent with genotype data obtained using a direct DNA sequencing technique. CONCLUSION: Of special interest are pathogenic missense mutations, since they generate variants that cause specific molecular phenotypes through protein destabilization. Overall, we discovered that the rs104893674 (C > A) variant chance in causing mixed-phenotype leukemia is relatively high.

Humans↗
PubMed1996

Molecular phylogeny of eastern Pacific sea cucumbers (Echinodermata: Holothuroidea) based on mitochondrial DNA sequence.

A molecular phylogenetic analysis of some Holothuroidea was undertaken in order to clarify the systematics and taxonomy of this class in the northeast Pacific. DNA sequence for portions of two mitochondrial genes, the large ribosomal subunit and cytochrome oxidase 1 was obtained from 16 species of sea cucumbers, including nine members of the family Cucumariidae. As reported for many mitochondrial genomes, a strong bias against G was noted in the coding strand at synonymous sites. In order to verify trees recovered in the presence of this bias, parsimony, maximum likelihood, distance, and log determinant methods were all employed. The resulting molecular phylogeny of the Cucumariidae, with a few exceptions, supported existing taxonomy which is based largely on the morphology of calcareous parts. In particular, evolutionary relationships among the brooding species were clarified. Our results confirm that C. pseudocurata Deichmann is distinct from C. curata Cowles and that these two species do not represent geographic variants of a single species. In fact C. pseudocurata appears to be conspecific with the more northerly distributed C. vegae Theel. We also clarify the identity of C. lubrica Clark and further suggest that C. fisheri astigmata (recently revised to Pseudocnus) should be considered a junior synonym of C. lubrica. The recent description of C. pallida Kirkendale and Lambert as a species, distinct from C. miniata (Brandt), is also supported. The resultant phylogenetic trees are consistent with multiple origins of direct development within the Cucumariidae. Finally, we suggest that an in-depth phylogenetic analysis of sea cucumber families will require examination of additional, more slowly evolving, regions of the genome(s).

Amino Acid Sequence↗
PubMed2003

Historical review: another 50th anniversary--new periodicities in coiled coils.

In 1953, Francis Crick and Linus Pauling both proposed models of supercoiled alpha helices ('coiled coils') for the structure of keratin. These were the first attempts at modelling the tertiary structure of a protein. Crick emphasized the packing mode of the side-chains ('knobs-into-holes'), which required a periodicity of seven residues over two helical turns (7/2) and a supercoil in the opposite sense of the constituent helices. By contrast, Pauling envisaged a broader set of periodicities (4/1, 7/2, 18/5, 15/4, 11/3) and supercoils of both senses. Crick's model became canonical and the 'heptad repeat' essentially synonymous with coiled coils, but 50 years later new crystal structures and protein sequences show that the less common periodicities envisaged by Pauling also occur in coiled coils, adding a variant packing mode ('knobs-to-knobs') to the standard model. Pauling's laboratory notebooks suggest that he searched unsuccessfully for this packing mode in 1953.

Amino Acid Motifs↗
PubMed2005

A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms and breast cancer risk.

INTRODUCTION: The gene XRCC1 (X-ray repair cross-complementing group 1) encodes a protein involved in DNA base excision repair. Two non-synonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) have been shown to alter DNA repair capacity in some studies in vitro. However, results of previous association studies of these two XRCC1 variants and breast cancer have been inconsistent. We examined the association between polymorphisms in XRCC1 and breast cancer in the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort, a large prospective study of cancer incidence in the USA. METHODS: Among the 21,965 women who were cancer-free in 1992 and gave blood between 1998 and 2001, 502 postmenopausal breast cancer cases were diagnosed between 1992 and 2001; 502 controls were matched to cases on age, race/ethnicity, and date of blood collection. Genotyping on DNA extracted from buffy coat was performed with Taqman. Conditional logistic regression was used to examine the association between each polymorphism and breast cancer risk controlling for breast cancer risk factors. We also examined whether factors associated with DNA damage, such as smoking and antioxidant intake, modified the association between XRCC1 polymorphisms and breast cancer. RESULTS: We observed a significant inverse association between Trp194 carriers (Trp/Trp and Trp/Arg) compared with Trp194 non-carriers in relation to breast cancer (Arg/Arg) (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.95). The inverse association between breast cancer and Trp194 carriers compared with non-carriers was slightly stronger among smokers (OR 0.47, 95% CI 0.24 to 0.94) than never smokers (OR 0.78, 95% CI 0.43 to 1.40). An increased risk associated with the Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was observed only among women who reported ever smoking cigarettes (OR 2.76, 95% CI 1.36 to 5.63), and not in women who were lifelong non-smokers (OR 0.64, 95% CI 0.33 to 1.26). No other factor examined modified the association between XRCC1 polymorphisms and breast cancer risk. CONCLUSION: Our results support the hypothesis that genetic variation in XRCC1, particularly in Arg194Trp, may influence postmenopausal breast cancer risk. In our study, genetic variation in XRCC1 Arg399Gln was associated with breast cancer risk only among women with a history of smoking cigarettes.

Aged↗
PubMed1988

Lack of cross-reactivity between variant T cell determinants from malaria circumsporozoite protein.

The discovery of polymorphism in the T cell determinants of the protein that covers the surface of malaria sporozoites, the circumsporozoite protein (CSP), may have a negative effect on the course of development of a sporozoite-derived anti-malaria vaccine. Comparison of CSP gene sequences from Plasmodium falciparum suggests, based on the lack of silent (i.e., synonymous) substitutions, that polymorphism is being biologically selected for in the field. Thus, variation in T cell determinant sequences may actually be a means of immune evasion. The central question addressed here is whether or not the natural polymorphisms found in three identified T cell determinants in the CSP gene of P. falciparum are immunologically significant with regard to T cell stimulation. In support of the immune evasion hypothesis, we show here that animals immunized with peptides based on one sequence (i.e., the 7G8 isolate) will not significantly respond when challenged with variant peptides based on other CSP sequences (i.e., the LE5 and We1 isolates). Polymorphism in T cell determinants thus indicates that infection with sporozoites will not necessarily boost immune (antibody help and/or proliferative) responses stimulated by prior infections or by a particular vaccine construct based on these determinants. The implications of these findings in regard to vaccine development are discussed.

Amino Acid Sequence↗
PubMed2001

Screening breast cancer patients for ATM mutations and polymorphisms by using denaturing high-performance liquid chromatography.

All 62 coding exons of the ATM gene, along with 10-20 bases of the intronic region flanking each exon, were screened for DNA base sequence alterations by using denaturing high-performance liquid chromatography (DHPLC) in a series of 52 breast cancer patients. Six (12%) of these patients exhibited a total of eight different novel germ-line mutations that do not represent common polymorphisms. Of these, three patients possessed four nonconservative missense mutations while two conservative missense and two synonymous mutations were detected in the other three patients. In addition, 43 patients were found to have a total of 141 DNA sequence variations representing 21 different common polymorphisms and rare variants. An analysis of the relationship between the presence of a novel ATM mutation and either patient demographics or tumor properties demonstrated a significant difference between African Americans (3/7 = 43%) and other ethnic groups (3/45 = 7%, P = 0.026). None of the other characteristics examined was found to be related to mutation status.

Adult↗
PubMed2005

Mutations of APC and MYH in unrelated Italian patients with adenomatous polyposis coli.

The analysis of APC and MYH mutations in adenomatous polyposis coli patients should provide clues about the genetic heterogeneity of the syndrome in human populations. The entire coding region and intron-exon borders of the APC and MYH genes were analyzed in 60 unrelated Italian adenomatous polyposis coli patients. APC analysis revealed 26 point mutations leading to premature termination, one missense variant and one deletion spanning the entire coding region in 32 unrelated patients. Novel truncating point mutations included c.1176_1177insT (p.His393_PhefsX396), c.1354_1355del (p.Val452_SerfsX458), c.2684C>A (p.Ser895X), c.2711_2712del (p.Arg904_LysfsX910), c.2758_2759del (p.Asp920_CysfsX922), c.4192_4193del (p.Ser1398_SerfsX1407), c.4717G>T (p.Glu1573X) and a novel cryptic APC exon 6 splice site. MYH analysis revealed nine different germline variants in nine patients, of whom five were homozygotes or compound heterozygotes. The mutations included 4 novel MYH missense variants (c.692G>A, p.Arg231His; c.778C>T, p.Arg260Trp; c.1121T>C, p.Leu374Pro; and c.1234C>T, p.Arg412Cys) affecting conserved amino acid residues in the ENDO3c or NUDIX domains of the protein and one novel synonymous change (c.672C>T, p.Asn224Asn). Genotype-phenotype correlations were found in carriers of APC mutations but not in carriers of biallelic MYH mutations, except for a negative correlation with low number of polyps. A distinctive characteristic of patients negative for APC and MYH mutations was a significantly (p<0.0001) older age at diagnosis compared to patients with APC mutations. Moreover, the proportion of cases with an attenuated polyposis phenotype was higher (p = 0.0008) among patients negative for APC and MYH mutations than among carriers of APC or biallelic MYH mutations.

Adenomatous Polyposis Coli↗
PubMed1997

Sequence variation in the hpd gene of nonencapsulated Haemophilus influenzae isolated from patients with chronic bronchitis.

The molecular diversity of protein D of nonencapsulated Haemophilus influenzae strains isolated from persistently infected patients with chronic bronchitis was studied by sequencing the hpd gene of four independently obtained isolates. The nucleotide (nt) sequences of the hpd genes of two strains were identical. The other two hpd sequences showed nt substitutions which were mostly synonymous. As a consequence the deduced amino acid (aa) sequences differed from the consensus sequence only by a few aa. No changes in the hpd genes were observed among the four variants of the four strains persisting in chronic bronchitis patients for 9, 11, 8 and 3 months, respectively, although variation in their major outer membrane proteins P2 and P5 occurred. We conclude that the hpd gene is conserved during chronic infections of nonencapsulated H. influenzae.

Amino Acid Sequence↗
PubMed2003

Transpecific polymorphisms in an inversion linked esterase locus in Drosophila buzzatii.

Nucleotide variation was studied in a 1.1 kb section of the coding region of an Esterase gene (Est-A) that maps in the center of the segments rearranged by polymorphic inversions in the cactophilic Drosophila buzzatii. We examine 30 homozygous second-chromosome lines differing in gene arrangement and three D. koepferae isofemale lines as outgroups. Our data show that Est-A is a highly polymorphic gene at both synonymous and replacement sites. Significant departures from homogeneity in the distribution of the ratio of silent polymorphism to divergence predicted by the neutral theory reveals a local excess of silent polymorphism. This is consistent with the presence of two apparent narrow peaks of elevated silent polymorphism surrounding nonconservative amino acid substitutions. These polymorphisms as well as others at synonymous and nonsynonymous sites are shared with D. koepferae. We suggest that the presence of shared nucleotide polymorphisms is probably due to interspecific gene flow and/or balancing selection acting on replacement variants and/or to a decreased probability of loss of ancestral polymorphisms caused by linkage to an adaptive inversion polymorphism. Recurrent mutation and persistence of neutral ancestral polymorphisms cannot, however, be ruled out. The analysis of the distribution of nucleotide variation among the three chromosomal arrangements sampled reveals that derived arrangements (J and JZ(3)) are less polymorphic than the ancestral ST, and that the widely distributed ST and J arrangements are genetically differentiated. However, a significant number of polymorphisms are shared between arrangements, suggesting frequent exchange either from gene conversion or from double crossovers in heterokaryotypes. Finally, our present results in combination with data of sequence variation at the breakpoints of inversion J suggest that this old gene arrangement has risen in frequency in relatively recent times.

Animals↗
PubMed2006

Emergence of a resistance-breaking isolate of Rice yellow mottle virus during serial inoculations is due to a single substitution in the genome-linked viral protein VPg.

The recessive gene rymv-1, responsible for the high resistance of Oryza sativa 'Gigante' to Rice yellow mottle virus (genus Sobemovirus), was overcome by the variant CI4*, which emerged after serial inoculations of the non-resistance-breaking (nRB) isolate CI4. By comparison of the full-length sequences of CI4 and CI4*, a non-synonymous mutation was identified at position 1729, localized in the putative VPg domain, and an assay was developed based on this single-nucleotide polymorphism. The mutation G1729T was detected as early as the first passage in resistant plants and was found in all subsequent passages. Neither reversion nor any additional mutation was observed. The substitution G1729T, introduced by mutagenesis into the VPg of an nRB infectious clone, was sufficient to induce symptoms in uninoculated leaves of O. sativa 'Gigante'. This is the first evidence that VPg is a virulence factor in plants with recessive resistance against viruses outside the family Potyviridae.

Genes, Viral↗
PubMed2005

Multigene tracking of quasispecies in viral persistence and clearance of hepatitis C virus.

AIM: To investigate the evaluation of hepatitis C virus (HCV) quasispecies in the envelope region and its relationship with the outcome of acute hepatitis C. METHODS: HCV quasispecies were characterized in specimens collected every 2-6 mo from a cohort of acutely HCV-infected subjects. We evaluated two individuals who spontaneously cleared viremia and three individuals with persistent viremia by cloning 33 1-kb amplicons that spanned E1 and the 5' half of E2, including hypervariable region 1 (HVR1). To assess the quasispecies complexity and to detect variants for sequencing, 33 cloned cDNAs representing each specimen were assessed by a combined method of analysis of a single-stranded conformational polymorphism and heteroduplex analysis. The rates of both synonymous and nonsynonymous substitutions for the E1, HVR1 and E2 regions outside HVR1 were analyzed. RESULTS: Serum samples collected from chronic phase of infection had higher quasispecies complexity than those collected from acute phase of infection in all individuals examined. The genetic diversity (genetic distance) within HVR1 was consistently higher than that in the complete E1 (0.0322+/-0.0068 vs -0.0020+/-0.0014, P<0.05) and E2 regions outside HVR1 (0.0322+/-0.0068 vs 0.0017+/-0.0011, P<0.05) in individuals with persistent viremia, but did not change markedly over time in those with clearance of viremia. For individuals with persistent viremia, the rate of nonsynonymous substitutions within the HVR1 region (2.76X10(-3)+/-1.51X10(-3)) predominated and gradually increased, as compared with that in the E1 and E2 regions outside HVR1 (0.23X10(-3)+/-0.15X10(-3), 0.50X10(-3)+/-0.10X10(-3)). By contrast, the rates of both nonsynonymous and synonymous substitutions for the E1 and E2 regions including HVR1 were consistently lower in individuals with clearance of viremia. CONCLUSION: HCV persistence is associated with a complexity quasispecies and positive selection of HVR1 by the host immune system.

Acute Disease↗
PubMed2001

The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants.

The pregnane X receptor (PXR)/steroid and xenobiotic receptor (SXR) transcriptionally activates cytochrome P4503A4 (CYP3A4) when ligand activated by endobiotics and xenobiotics. We cloned the human PXR gene and analysed the sequence in DNAs of individuals whose CYP3A phenotype was known. The PXR gene spans 35 kb, contains nine exons, and mapped to chromosome 13q11-13. Thirty-eight single nucleotide polymorphisms (SNPs) were identified including six SNPs in the coding region. Three of the coding SNPs are non-synonymous creating new PXR alleles [PXR*2, P27S (79C to T); PXR*3, G36R (106G to A); and PXR*4, R122Q (4321G to A)]. The frequency of PXR*2 was 0.20 in African Americans and was never found in Caucasians. Hepatic expression of CYP3A4 protein was not significantly different between African Americans homozygous for PXR*1 compared to those with one PXR*2 allele. PXR*4 was a rare variant found in only one Caucasian person. Homology modelling suggested that R122Q, (PXR*4) is a direct DNA contact site variation in the third alpha-helix in the DNA binding domain. Compared with PXR*1, and variants PXR*2 and PXR*3, only the variant PXR*4 protein had significantly decreased affinity for the PXR binding sequence in electromobility shift assays and attenuated ligand activation of the CYP3A4 reporter plasmids in transient transfection assays. However, the person heterozygous for PXR*4 is normal for CYP3A4 metabolism phenotype. The relevance of each of the 38 PXR SNPs identified in DNA of individuals whose CYP3A basal and rifampin-inducible CYP3A4 expression was determined in vivo and/or in vitro was demonstrated by univariate statistical analysis. Because ligand activation of PXR and upregulation of a system of drug detoxification genes are major determinants of drug interactions, it will now be useful to extend this work to determine the association of these common PXR SNPs to human variation in induction of other drug detoxification gene targets.

Alleles↗
PubMed2005

L1 sequence of a new human papillomavirus type-58 variant associated with cervical intraepithelial neoplasia.

The present study on molecular characterization of a human papillomavirus (HPV) isolated in Central Brazil describes the L1 gene sequence from a new variant of HPV-58, the isolate Bsb-02. The sample was from a smear obtained from a woman with cervical intraepithelial neoplasia grade II. The whole L1 gene from isolate Bsb-02 was sequenced automatically, showing 99.1% nucleotide identity with the gene from the HPV-58 reference. The clustering between Bsb-02 and HPV-58 reference sequence was also supported by phylogenetic analysis. Fourteen nucleotide substitutions were observed: eight were synonymous and six were associated with amino acid substitutions. A10V and V144I have not been previously described. At GenBank, the only complete L1 sequence from HPV-58 in addition to the HPV-58 reference one is that of Bsb-02. These data provide information that may be relevant to HPV diagnosis and to rational vaccine strategies. HPV variants may also be associated with host immune responses and with the risk of cervical neoplasia.

Amino Acid Sequence↗