Relationships In Mice And Humans

Testis-expressed 19 (TEX19)

The Tex19 is the gene which was at first discovered in the germ cells of mice and is referred as a specific gene present in mammals (Wang et al., 2001; Kuntz et al., 2008). In case of duplication of the Tex19 gene in the rodents, it is seen that the process has resulted to generate paralogue pairs named as Tex19.1 and Tex19.2 in rats and mice whereas in humans a single genetic form is present. The location of the Tex19.1 and tex19.2 are on the 11th chromosome in case of rodents whereas in case of humans Tex19 is seen to be located on the 17th chromosome (Fig 1.7). The murine Tex19.1 and the human Tex19 are seen to have link with various other genes such as CD7, UTS2R and Sectm1. Further, Tex19 present in both the mice and humans are seen to be oriented in a similar line with the centromere where it is separated by similar distance from the UTS2R. The highlighted information supports that the human Tex19 is therefore in close relation with the murine Tex19.1 and refers that it is the Tex19 is the orthologous human gene in relation to the form of Tex19.1 (Kuntz et al., 2008). This aspect of gene comparison is significant in biology dissertation help, as it underscores the genetic similarities and differences between species.

The location of the Human Tex19 is on the 17th chromosome and the other paralogous genes that are Tex19.1 and Tex 19.2 are present on the 11th chromosome. In comparison to the paralogous gene that is Tex19.2, it is seen that the Tex19.1 which is the human orthologue gene is located in close position near the human Tex19 in a similar manner (Kuntz et al., 2008).

The Tex19 orthologue is seen to have undergone a change through duplication process on rodent for generating pair of gene paralogue named as Tex19.1 and Tex19.2 (Kuntz et al., 2008). However, the murine genes are seen to be expressed differently with the Tex19.1 gene expressed in the placenta, adult testis and early embryo in a certain pattern that matches the Oct4gene which is pluripotent marker and expression of Tex19.2 gene is seen to be restricted to the adult testis and the gonadal testis (Kuntz et al., 2008). However, way the expression of the two genes is controlled is seen to be distinct in nature (Hackett et al., 2012). The expression of Tex19.1 gene is seen in the embryonic stem cells (ESCs) and this might be able to interfere with the functional role of the stemness (Kuntz et al., 2008). There are no overt proliferative defects in the Tex19.1ESCs and no form of overtly phenotypic defects are seen for them in case of expression in the spermatogonial germ cells (Tarabay et al., 2013; Öllinger et al., 2008). The initial analysis regarding the expression of human Tex19 informs that it is orthologous related to tex19.1 as it is seen to be expressed in the human ESCs. The cytoplasm present in the Tex19.1 is large in nature and its location appears to be on the spermatogonial germline cells present in the seminiferous tubules thus suggesting that relates its function to be germline-specific ( Öllinger et al., 2008; Kuntz et al., 2008; Tarabay et al., 2013).

The Tex19 expression in the human cells is seen in the testis tissues of the adults and the placental cells (Kuntz et al., 2008). In a recently mentioned study, Tex19 has not been found in the normal tissues but in the testis tissue (Reichmann et al., 2013). In contrast, Tex19.2 is seen to be expressed in a different way from the murine Tex19.1 that informs different functioning during the course of development of embryo (Yang et al., 2010). The other studies are seen to indicate an essential functioning of tex19.1 in which the loss of the gene shows postponement of development of embryo (Öllinger et al., 2008). The deletion of Tex19.1 is seen to create defects in the meiotic synapsis of chromosome and spermatogenesis (Öllinger et al., 2008). Further, the deletion of tex19.1 results in infertility among males which also impairs their process of spermatogenesis (Tarabay et al., 2013). Thus, this informs that the existence of Tex19.1 is vital for the placental development in women and spermatogenesis in males (Öllinger et al., 2008). Other studies have informed that tex19.1 has the key function of executing transposable regulation of elements. In the initial stage of spermatogenesis, the deletion of Tex19.1 in the testis has resulted in creating consistent change of the genes that are encoded to serve the purpose of synaptonemal complex and meiotic recombination like SPO11, REC8 and Smc1β (Öllinger et al., 2008). In comparison to this, in case of long terminal repeats, an important upregulating change is been seen in the long terminal repeats (LTRs)-retrotransposon MMERVK10C but the elevation in the MMERVK10C elements has the ability to drive defects in spermatogenesis (Öllinger et al., 2008). The study has further supported that the Tex19.1 play the role of repressing retrotransposon among the females in their placenta. The Tex19.1 deletion in the cells of the placenta increases the expression of LINE-1 (long interspersed nuclear element). The increase in the level is seen to contribute deregulation of retrotransposons which acts subsequently to the dysfunction of the placenta (Reichmann et al., 2013). Thus, this findings refers that the Tex19.1 is a regulated part present in the germline for controlling transposable elements as well as sustain the balance of the genomic through consecutively generating (Reichmann et al., 2013; Öllinger et al., 2008). Most current studies have informed that the Tex19 function to suppress transposable elements is able to be linked with the functioning of the flanking gene that is secreted and transmembrane 1 gene (sectm1) that has the function to get involved for effective regulation of retrotransposon activity (Bianchetti et al., 2015).

The Tex19 depletion in certain type of cancer cell lines in vivo and in vitro is seen to cause restriction of self-renewal or proliferation or reduction of volume of tumour thus indicating Tex19 is needed for self-renewal potential or cancer cell proliferation. The Tex19 is also seen to be present in the cytoplasm and nucleus in both normal testis and cancerous cells. In the cancer cells, the localisation is seen to switch in the form of context-dependent fashion. On transcriptome analysis of the depleted cells of Tex19, it informs altered transcript level of various proliferation or cancer associated genes which suggests that Tex19 is able to control the proliferation of an oncogenic gene through the transcription or transcript regulation pathway. Further, the survival analysis regarding the high versus low Tex19 expressing tumours informs that the expression of Tex19 is able to be linked with the prognostic outcomes in various tumour types (Planells-Palop et al., 2017).

Tex19 and Cancer

The Tex19 is referred by Feichtinger et al. for the first time as a form of CT gene in 2012. In this study, the two different approaches being used are done for identification of set of CT genes that are meiosis-related. In the first strategy, a manual curation is done for the genes mentioned in the literature with the reported meiosis-specific expression. In the second approach, a multi-step bioinformatics analysis is being used. The human orthologues were seen to be allocated to a range of 744 mouse meiosis-specific genes is identified in the previously executed studies (Chalmel et al., 2007). The genes in the non-Central Nervous System Expressed Sequence tag (EST) or non-testis libraries are dismissed and the one which lacked representation in the cancer EST libraries were also dismissed. The candidates present were seen to be tested by the RT-PCR and the patterns of their expression were cross-compared in the form of meta-analysis including cancer microarray data derived from patients. The Tex19 is seen to be defined in the form of cancer-selective CT gene that shows the expression in the thymus and the testis in case of normal tissues as well as in different ranges of cancer samples and cancer cell lines. The positive deletion of the Tex19 present in the thymus is seen to be explained through the process of atrophy according to which the tissue develops experiences with ageing (Feichtinger et al., 2012).

Zhong et al. after executing check of the presence of Tex19 genes in the normal tissues informed that 60% of the tumours in the bladder are positive tex19 when they were analysed through the process of RT-PCR or RT-qPCR. The Te19 protein is also seen to be detected in the samples of cancer cells and its presence in them was seen to statistically higher in number at a higher-grade in comparison to low-grade tumours. In the study sample, it has been seen that Tex19 is detected in the cancer cell lines in the bladder at both the protein level as well as in the mRNA (Zhong et al., 2015). Thus, all of these studies informed that Tex19 may be important or key biomarkers for cancer diagnosis or prognostics. Further, Tex19 functioning in the cancer cells is going to provide a valuable platform for the researchers to develop a novel approach for providing deep insight into the aetiology of different types of cancer.

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This information is supported by the findings derived in case of the tumours in Drosophila melanogaster where it is found that the tumours act to activate larger cohort of germline of the genes in the process of oncogenesis and some of these genes are essential for the species for their tumour progression. The analysis of the gene expression done in case of human tumour informs that similar germline gene patterns activation is apparent while intergerring possible functional requirement.

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