Analysis Of Human Papillomavirus Type34 Variants In Individual

Cervical cancer （CC） is one of the most common cancer in women worldwide. It is a serious threat to women’s health worldwide. The development of CC is associated with persistent infection by carcinogenic genotypes of HPV. All over the world, more than 200,000 women die of CC each year. In the developing countries, CC is a multiple gynecological tumor. There are about 150,000 new cases per year in China. According to the association between HPV infection and CC, HPV types are divided into high-risk HPV, possible high-risk HPV and low-risk HPV. High-risk HPV types, namely HPV16,18,31,33,35,39,45,51,52, 56,58,59 and 68, which often lead to malignant tumors of cervix uteri. In Europe countries, HPV16 and HPV18 are the most predominant prevalent types associated with CC. HPV epidemiological studies in some regions in China show that CC is associated with HPV16, HPV52 and HPV58 infection. Worldwide epidemiological studies indicate that HPV16 and HPV18 are the most carcinogenic types within high-risk HPV, being responsible for approximately 50% and 20% of cervical cancer respectively. Low-risk HPV, such as types 6, 11 and 34, which are mainly linked to benign genital warts.It has been recognized that HPV E6 protein and HPV E7 protein play an important role in carcinogenic mechanisms of molecular biology. The main function of HPV-E6 gene is that it encodes protein which have a activity of biotransformation. E6 protein is mainly located in the nucleus, E6 protein encodes 151 amino acids and has a 18KD molecular weight. There are four Cys-X-X-Cys conserved sequences which are involved in zinc binding region and cell transformation. HPV-E6 protein and p53 tumor suppressor gene product to form a com- plex, HPV-E6 protein product bind p53 protein which act as inhibit the degradation the cell cycle negative regulatory function and blocking apoptosis. It is possible that E6 protein induces malignant transformation of cells and cell immortalization. In addition, E6 protein is a multifunctional protein in the cell that can interact with a variety of proteins.The main function of E7 protein destroys retinoblastoma protein （pRb） and releases E2F transcription factor. E2F transcription factor activates cell cycle regulatory genes. These combined effect makes DNA-damaged cells proliferative excessive and turns to carcinogenic cells.Therefore, E6/E7 gene mutation related to HPV oncogenic capacity directly. Low-risk HPV infection that cause benign genital warts which do not cause high mortality rate compared with that high-risk HPV infection, but low-risk HPV infection bring great injury to human health and also bring enormous burden of disease. It is huge impact on the health which can not be underestimated. Therefore, research on low-risk HPV infection, especially clarify specific low-risk types of HPV are more urgent, which help us better understand its characteristics and traits of the infection and reduce the incidence of disease and disease burden.Researchs on low-risk HPV, especially for specific low-risk HPV infection makes to understand the presence of variants and variation of amino acid residues. In order to help us understand the host after the generation mechanism and immunity escape mechanism.In the present study, the DNA samples of HPV34 cervical cells were extracted and then carry out Next Generation Sequencing （NGS）. The sequencing depth was 24Gb, including the high quality FASTQ sequences of 241,568,984, and the HPV34 sequence of 3730. In order to determined variants and the variation of amino acid residues, HPV34 sequence are compared with the reference sequence （NC₀01587）.The results show that there are 15 variants in the HPV34, and the polymorphism is up to 20. Most nucleic acid variants cause variation of amino acid residues. We also observed linkage variation of 7 consecutive adjacent sites,15 kinds of nucleic acid polymorphism, polymorphism of amino acid residues for 14.2 consecutive adjacent loci linked variation and nucleic acid polymorphism for three, amino acid residues polymorphism for two. Thus, at least 15 variants of the in HPV34 individual.