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Genetic Engineering
Published in Shintaro Furusaki, John Garside, L.S. Fan, The Expanding World of Chemical Engineering, 2019
In bacteria, proteins are coded by an uninterrupted stretch of DNA. In contrast, eucaryotic genes are often disrupted by non-coding sequences (intron), and freshly produced messenger RNA (primary transcript) is modified through three main processing steps including 5’-capping, poly A tail addition and splicing before it exits the nucleus. By splicing, intron sequences are removed and coding sequences (exon) joined together. After splicing, eukaryotic messenger RNA is functional (Figure 12.6). Therefore, to produce an eucaryotic gene product in E. coli, complementary DNA to the matured messenger RNA after splicing is enzymatically synthesized by reverse-transcriptase of RNA tumor viruses. Then, a DNA product named complementary DNA (cDNA) is ligated to a suitable vector and E. coli is transformed. To produce abundant amounts of specific proteins in E. coli or other particular host organisms, many expression systems have been designed. Since promoters of eucaryotic origin do not work in E. coli, the regulatory sequences have to be changed to that of E. coll. Now, strong and inducible promoters such as the E. coli lactose operon (lac) and tryptophan operon (trp) are used (Figure 12.7). By using these expression systems, cloned gene products can be produced with up to 30% of E. coli total cellular protein under suitable conditions. As shown in Figure 12.7, gene expression from lac and trp promoters can be induced by simply adding inducing chemicals (inducer) to the culture medium.
Naturally Occurring Polymers—Animals
Published in Charles E. Carraher, Carraher's Polymer Chemistry, 2017
It appears that another way to gain complexity is the division of genes into different segments and by using them in different combinations, increasing the possible complexity. These protein coding sequences are known as exons and the DNA in between them as introns. The initial transcript of a gene is processed by a spliceosome that strips out the introns and joins the exons together into different groupings governed by other active agents in the overall process. This ability to make different proteins from the same gene is called alternative splicing. Alternative splicing is more common with the higher species. Related to this is the ability of our immune system to cut and paste together varying genetic segments that allow the immune system to be effective against unwanted invaders.
A Survey of QSAR Studies
Published in Tanmoy Chakraborty, Lalita Ledwani, Research Methodology in Chemical Sciences, 2017
Seema Dhail, Tanmoy Chakrborty, Lalita Ledwani
DNA acts as the genetic material in each living organism. It consists of billions of nucleotides containing numerous genes, which can express several different types of proteins. DNA consists of exons and introns. Exons are the protein-coding regions, and introns are the noncoding regions. DNA undergoes transcription process and gives rise to mRNA; further, it undergoes translation process that ultimately gives rise to specific proteins. Splice junction sites are also present, and they act as boundaries where splicing occurs. Chanin et al. (2009) developed a computational approach for the recognition of DNA splice junction sites. They transformed the DNA sequences to sequences of binary numbers by converting each nucleotide’s adenine (A), tyrosine (T), guanine (G), and cytosine (C) as 0001, 0010, 0100, and 1000, respectively. Each entry of the data set describes information surrounding the splice junction site, mainly, 15 nucleotides upstream and 32 nucleotides downstream. Approximately 1424 human DNA sequences data set is made by them that is divided into two portions: i) a training set of 1000 sequences and ii) a testing set of 424 sequences. Various types of predictive models were developed using three different types of learning algorithm, which consists of i) self-organizing map, ii) back propagation neural network, and iii) support vector machine.
Study of age-related changes in Middle ear transfer function
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2019
Lei Zhou, Na Shen, Miaolin Feng, Houguang Liu, Maoli Duan, Xinsheng Huang
There are numerous studies on otosclerosis (OS) and OP. Swinnen et al. found that patients with osteogenesis imperfecta are at risk of hearing loss (Swinnen et al. 2012). Clark et al. studied the relationship between hearing loss and bone mass in 369 females drawn from a population of rural women aged 60–85 years, and found that a consistent association between femoral neck bone mass and age-related hearing loss (Clark et al. 1995). Atan et al. investigated OS and OP using a bone mineral density test in postmenopausal women, and noted a tendency for OP in patients with OS (Atan et al. 2016). Clayton et al. reported a positive association between OS and OP in 200 women aged 50–75 years (Clayton et al. 2004). Mckenna et al. found that some cases of OS and OP shared a functionally significant polymorphism in the Sp1 transcription factor binding site in the first intron of the COL1A1 gene (Mckenna et al. 2004). Quesnel et al. used an anti OP drug to treat sensorineural hearing loss (SNHL) related to OS, and achieved stabilization in their treatment groups (Quesnel et al. 2012). These studies demonstrate a correlation between OP and OS, a common cause of conductive hearing loss; these two diseases are both metabolic bone abnormality. It is possible that ossicles may also undergo metabolic abnormalities, such as OP, in common with other bones. Furthermore, the soft tissue in the middle ear may develop age-related changes.
Discovery of genetic risk factors for disease
Published in Journal of the Royal Society of New Zealand, 2018
In 1999 I moved to the Queensland Institute for Medical Research (QIMR) to lead a molecular genetics laboratory within a group studying genetic contributions to human traits and diseases. The Brisbane group had many years’ experience working with twin families to estimate genetic contributions for many conditions. We embarked on a significant programme to collect biological samples from twin families and disease cohorts for mapping studies. Risk factors for melanoma include genes associated with mole count and pigmentation. While linkage studies lack power to detect genetic risk factors for most complex human traits and diseases, some genes affecting pigmentation have sufficiently large effects that the location of these genes can be detected. Using linkage mapping, we mapped the major locus for blue/brown eye colour to chromosome 15 in the region of the oculocutaneous albinism II (OCA2) gene (Zhu et al. 2004). Subsequent fine mapping studies identified a single SNP (rs12913832) which accounted for 95% of the variation in blue/brown eye colour (Sturm et al. 2008). This SNP is located 21 kb upstream of OCA2 within an intron of the adjacent gene, HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2), in an enhancer regulating OCA2 transcription (Visser et al. 2012). The allele for blue eyes reduces the recruitment of transcription factors helicase-like transcription factor (HLTF), lymphoid enhancer-binding factor 1 (LEF1), and melanogenesis associated transcription factor (MITF), and reduces interactions between the enhancer and the promoter of OCA2 (Visser et al. 2012).
A feasible direction algorithm for nonlinear second-order cone programs
Published in Optimization Methods and Software, 2019
Alfredo Canelas, Miguel Carrasco, Julio López
Next, we describe four benchmark datasets that will be used to solve numerically problem (27), these data were scaled to the interval More information on these datasets can be found in the UCI Repository [3]. Wisconsin Breast Cancer (WBC): It contains m=569 tissue samples ( diagnosed as malignant and as benign tumors) described by n=30 continuous features.Pima Indians Diabetes (DIA): It contains m=768 samples ( tested as positive and tested as negative), with n=8 features.German Credit (GC): It presents m=1000 granted loans, good and bad payers in terms of repayment, with n=24 attributes.Splice (SPL): It contains 1000 randomly selected instances (from the complete set of 3190 splice junctions), with labeled as intro-exon and as exon-intron, described by n=60 categorical variables (the gene sequence).