Biology in Genomics
Ben Hui Liu in Statistical Genomics, 2017
Mendel discovered the genetic segregation of simple traits using crosses of garden peas expressing different characteristics. This chapter discusses genetics basics relevant to genomics. These include: meiosis and recombination in cytogenetics, gene frequency and additive and dominant genetic effects in population and quantitative genetics and DNA sequence and gene expression in molecular genetics. Mendelian genetics is concerned with classical simple trait segregation theory and simple linkage genetics. Mendelian laws include the law of segregation and the law of independent assortment. For traits controlled by a single gene and having simple heredity, each somatic cell of an individual carries a pair of alleles. There are two regular types of cell division in biological development: mitosis and meiosis. Both genetic and cytological techniques have been used to study genetic recombination and chiasmata formation. Population genetics focuses on the frequencies, distribution and origins of genes in populations.
Restarting DNA Replication by Recombination
James E. Haber in Genome Stabilty, 2013
For almost 100 years, scientists have been fascinated with the mechanisms that promote crossing over in meiosis. It is much more recently that we have begun to understand that the mechanisms that underlie meiotic recombination also account for the ways organisms from bacteria to people are able to cope with damaged and broken chromosomes in all types of cells. Genetic recombination is in fact essential for the viability of human cells, and defects in recombination and repair mechanisms are frequently associated with the loss of genetic integrity that is found in cancer cells. The fundamental mechanisms of genetic recombination and repair are conserved in bacteria, archaea, and eukaryotes.
Evolutionary Variation in Proteins
John Kuriyan, Boyana Konforti, David Wemmer in The Molecules of Life, 2012
Variation and natural selection, the two centrally important tools of evolu-tion, operate ultimately at the level of protein and RNA function. Changes in the nucleotide sequences of genes, brought about by errors in replication, by genetic recombination, or by damage infl icted by the environment, fi nd expression in the altered sequences of proteins and RNA. In this chapter, we shall study how variation in the sequences of related proteins is refl ected in their three-dimensional structures. We fi rst discuss a very important principle, which is that all the information that is required to fold a protein into a specifi c three-dimensional structure is contained within the sequence of the protein. Despite this, the general shape of folded proteins is remarkably tolerant of changes in the amino acid sequence. Th is tolerance allows sequence variation to accumulate without disrupting the ability of proteins to fold and function. Th ese changes eventually alter the properties of proteins and thereby provide the functional variation that natural selection draws upon. We next discuss how the analysis of the potentially limitless variety of proteins in nature is simplifi ed in practice by the fact that proteins are constructed in a modular fashion from combinations of domains, from a large but limited repertoire. Finally, we illustrate the versatility with which nature creates complicated and highly specialized proteins by exploiting variation in the sequences of these domains.
Coxsackievirus A16
Published in Human Vaccines & Immunotherapeutics, 2014
Qunying Mao, Yiping Wang, Xin Yao, Lianlian Bian, Xing Wu, Miao Xu, Zhenglun Liang
Coxsackievirus 16 (CA16) is one of the major pathogens associated with hand, foot, and mouth disease (HFMD) in infants and young children. In recent years, CA16 and human enterovirus 71 (EV71) have often circulated alternatively or together in the Western Pacific region, which has become an important public health problem in this region. HFMD caused by CA16 infection is generally thought to be mild and self-limiting. However, recently several severe and fatal cases involving CA16 have been reported. Studies have shown that co-infection with CA16 and EV71 can cause serious complications in the central nervous system (CNS) and increase the chance of genetic recombination, which may be responsible for the large HFMD outbreak in Mainland China in 2008. For these reasons, recent studies have focused on the virological characteristics of CA16 and the development of CA16-related diagnostic reagents and vaccines.
Phylogenetic analysis of the major causative agents of hand, foot and mouth disease in Suzhou city, Jiangsu province, China, in 2012–2013
Published in Emerging Microbes & Infections, 2015
Chao Zhang, Rui Zhu, Yong Yang, Yudan Chi, Jieyun Yin, Xinying Tang, Luogang Yu, Chiyu Zhang, Zhong Huang, Dongming Zhou
Hand, foot and mouth disease (HFMD) is a serious public health problem that has emerged over the past several decades. Pathogen detection by the Chinese national HFMD surveillance system has focused mainly on enterovirus 71 (EV71) and coxsackievirus A16 (CA16). Therefore, epidemiological information regarding the other causative enteroviruses is limited. To identify the pandemic enterovirus in Suzhou, Jiangsu province, China, clinical samples from patients with HFMD were collected from 2012 to 2013 and analyzed. The results revealed that CA16 was the most dominant HFMD pathogen in 2012, whereas CA6 and CA10 were the dominant pathogens in 2013. Phylogenetic analysis revealed that the C4a sub-genogroup of EV71 and the B1a and B1b sub-genogroups of CA16 continued to evolve and circulate in Suzhou. The CA6 strains were assigned to six genotypes (A–F) and the CA10 strains were assigned to seven genotypes (A–G), with clear geographical and temporal distributions. All of the CA6 strains in Suzhou belonged to genogroup F, and there were several lineages circulating in Suzhou. All of the CA10 strains in Suzhou belonged to genogroup G, and they had the same genetic origin. Co-infections of EV71/CA16 and CA6/CA10 were found in the samples, and bootscan analysis of 5′-untranslated regions (UTRs) revealed that some CA16 strains in Suzhou had genetic recombination with EV71. This property might allow CA16 to alter its evolvability and circulating ability. This study underscores the need for surveillance of CA6 and CA10 in the Yangtze River Delta and East China.
Adenoviral vectors transduce alveolar macrophages in lung cancer models
Published in OncoImmunology, 2018
Darinee D. Tippimanchai, Kyle Nolan, Joanna Poczobutt, Gregory Verzosa, Howard Li, Hannah Scarborough, Jing Huang, Christian Young, James DeGregori, Raphael A. Nemenoff, Stephen P. Malkoski
Adenoviral vectors expressing Cre recombinase are commonly used to initiate tumor formation in murine lung cancer models. While these vectors are designed to target genetic recombination to lung epithelial cells, adenoviruses can infect additional cell types that potentially influence tumor development. Our goal was to explore the consequences of adenoviral-mediated alveolar macrophage (AM) transduction in a Kras-initiated lung tumor model. As expected, treatment of animals harboring the KrasLSL-G12D allele and an inducible green fluorescence protein (GFP) tracking allele with an adenoviral vector expressing Cre recombinase under the control of the cytomegalovirus (CMV) promoter (Ad5-CMV-Cre), caused GFP-positive lung adenocarcinomas. Surprisingly, however, up to 70% of the total GFP+ cells were AM, and GFP+ AM could be detected 6 months after tumor initiation, and transduced AM demonstrated Kras activation and increased proliferation. In contrast, recombination was not detected in other immune cell populations and AM recombination could be eliminated by tumor initiation with an adenovirus expressing Cre recombinase under the control of the surfactant protein C (SPC) promoter. In addition, AM isolated from KrasLSL-G12D animals and transduced by Ad5-CMV-Cre ex vivo displayed prolonged survival in vitro and increased the growth of murine lung adenocarcinoma CMT/167 cells when co-injected in an orthotopic flank model. Given the importance of the immune system in tumor development and progression, inadvertent AM transduction by Ad5-CMV-Cre merits careful consideration during lung cancer model selection particularly if studies evaluating the tumor-immune interactions are planned.
Related Knowledge Centers
- Crossing Over
- Recombinant DNA
- Genetic Phenomena
- Artificial Gene Fusion
- Gene Transfer Technique
- Eukaryota
- Immunoglobulin Genes