Gene

“ Hence whatever we learn about those hereditary elements that stand for defects, we learn just as much about the behavior of the normal partners of those elements. In a word, heredity is not confined to a study of the shuffling of those genes that produce abnormal forms, but is equally concerned with what is going on when normal genes are redistributed. This method of pitting one gene against the other furnishes the only kind of information relating to heredity about which we have precise knowledge. ”

“ Since a single gene is usually made up of several hundred bases, it is easy to imagine the infinite variety of genes that could exist by simply changing the order of the four bases several hundred times.
Figure 26
THE GENE-ACTION SYSTEM
Not all genes in the cells of a living organism are active. ”

“ Specifically, if a group of genes shows a consistent pattern of different expression levels in sick subjects and a control group, then that gene is likely a strong candidate of playing a pathogenic role. ”

“ Mutations, sort of unexpected changes, can take place in either the chromosomes or the genes. You see, when this one cell starts dividing, every gene makes a copy of itself; but, sometimes, the copy is a little different from the original. ”

“ Phenotypic profile comparison and phenotype promotion.Multiple EQ descriptions annotated to a genotype comprise a phenotypic profile, and these profiles can be compared using subsumption logic. Phenotypes annotated to genotypes are propagated to their allele (s) , and in turn to the gene, indicated with upward arrows. Similarity is analyzed between any two nodes of the same type, such as between gene A-vs-B, allele A3-vs-B1, genotypes A1/A1-vs-A3/A3, or A3/A3-vs-B1/B1. Genotypes are shown as rounded boxes, alleles as circles, and genes as squares. ”

“ The recognition that disease genes are not a homogenous subset of human genes, and that essential genes cannot be excluded from consideration as candidates for all types of human disease genes, will aid in the identification of candidate disease gene loci for a variety of human diseases. ”

“ From simple, organic compound through the simple colloid, the protein, the primitive protoplasm, the simplest unicellular organism, the flagellate and—then the great jump into the structure of the gene, the ferreting-out of that intricate, vital combination that gave man life and maintained it. ”

“ In man and in domesticated animals we find that individuals appear occasionally that are defective in one or another respect. Some of the defects are inherited. Rarely a new one appears that has not been seen before. But the majority of them are reappearances of characters that have been carried under the surface as recessive genes in the germ-plasm. Today we recognize that each of these modifications, if recessive, has first arisen as a mutational change in a single gene before it appeared on the surface as a character by the coming together of two such genes. ”

“ A question that is being vigorously debated at this time concerns the possible effects of selection on the hereditary factors. Are the genes fixed both qualitatively and quantitatively or does a given gene vary in potency under different conditions and in different individuals? In the former case selection can only separate the existing genes into separate pure strains. But if the gene be quantitatively variable, then selection will result in the establishment of new types. ”

“ The similar physiology and genome structure between the mouse and human facilitate ortholog comparison and functional identification between the two species. To determine if differences exist between essential and non-essential disease genes we examined several parameters in our analyses, including the physiological systems affected by each disease gene, the connectivity of each gene in protein-protein interaction networks, and the genetic mechanisms by which genes cause human disease. ”

“ Also, when we did not consider specific gene loci and ranked all genes globally by our score, we could identify genes that show high extent of pleiotropy and participate in the physiological pathogenic processes of many diseases [28] . In addition, the successful identification of the common genes involved in many diseases in the context of network indicates the phenotypic interdependency, cooccurrence and shared pathophysiology between different disorders. This study provides a novel, effective and easy-implemented algorithm for the prioritization of candidate disease genes. ”

“ Certain limitations to the law are met with because the relatively small number of chromosomes involves linkage of genes, because of the occasional interchange of groups of genes between homologous chromosomes, and because the relative activity or potency of any particular gene may differ in different races, and, finally, because the normal activity of any given gene may be modified or inhibited by the action of other genes. ”

“ Housekeeping genes are required for the maintenance of essential basal cellular functions and consequently, under normal conditions, they are expressed in all cells regardless of tissue type or developmental stage [54] . They are especially interesting because they represent the minimal set of genes required to sustain life and they can be used as comparative controls for experimental and computational studies [54] , for example, to assess the suitability of transcriptome datasets for gene discovery [50] . ”

“ A direct interaction between a pair of proteins either has been observed or has not been observed yet. The relationships between a candidate gene (encoding the corresponding protein) and all other genes/proteins can be thus defined. Such information can also be obtained from other data sources. For example, gene expression data can be transformed into gene co-expression networks by connecting genes with similar expression patterns. To represent known knowledge from biological pathways, a simple network can be built by connecting genes (or their products) that coexist in any pathway. ”

“ Of course if a dominant character is advantageous in itself, it will have a better chance of spreading through the race, than will an advantageous recessive character, because every hybrid that carries one dominant gene shows also the character, which increases the chance that it will propagate and spread the genes. ”

“ In this study, we propose an approach to prioritize candidate genes by integrating data of gene expression level, protein-protein interaction strength and known disease genes. Our method is based only on two, simple, biologically motivated assumptions—that a gene is a good disease-gene candidate if it is differentially expressed in cases and controls, or that it is close to other disease-gene candidates in its protein interaction network. We tested our method on 40 diseases in 58 gene expression datasets of the NCBI Gene Expression Omnibus database. ”

“ Once the information from a data source is represented by a network, the relationship between a candidate gene and a disease can be measured by the relationship between the candidate gene and all known disease genes. ”

“ This annotation and search method provides a novel and efficient means to identify gene candidates and animal models of human disease, which may shorten the lengthy path to identification and understanding of the genetic basis of human disease.==Abstract== Author SummaryModel organisms such as fruit flies, mice, and zebrafish are useful for investigating gene function because they are easy to grow, dissect, and genetically manipulate in the laboratory. ”

“ In cases when one disease corresponds to more than one experiment (disease-control datasets) , the score vectors for a given disease were added together to obtain a combined s-score. Then the genes in each candidate gene set of a disease can be ranked according to their s-cores, while the top h genes in the ranking could be predicted as associated with this disease. ”

“ These datasets represent the gene expression levels of 40 distinct diseases. Our human protein interaction data comes from the STRING database of the human genome and proteome. We got the data on disease genes of the mentioned 40 diseases from the OMIM database. First, we predicted disease genes within disease-associated loci only based on gene expression levels and protein-protein interactions. ”

“ A few general theories from quantitative genetics form the basis of these genetic mechanisms (Falconer 1981) . First, an animal's phenotype is the result of its genotype and the environment in which it developed. ”

“ All the processes of which I have spoken are accomplished by means of cell-divisions, and in the one cell-union which occurs in fertilisation. If we could watch [Pg 19] the factors segregating from each other in cell-division, or even if by microscopic examination we could recognize this multitudinous diversity of composition that must certainly exist among the germ-cells of all ordinary individuals, the work of genetics would be much simpler than it is. ”

“ To make clear the application of the terms chemical and mechanical to the problem of Genetics the nature of that problem must be more fully described. In its most concrete form this problem is expressed in the question, how does a cell divide? If the organism is unicellular, and the single cell is the whole body, then the process of heredity is accomplished in the single operation of cell-division. Similarly in animals and plants whose bodies are made up of many cells, the whole process of heredity is accomplished in the cell-divisions by which the germ-cells are formed. ”

“ This result suggests that the known disease genes were averagely ranked top 24.6% of the candidates by integrating gene expression levels with protein interactions, whereas they ranked top 41.8% and 25%, on average, respectively, if only gene expression data or protein interaction network were utilized. ”

“ GENOME EDITING
For decades, people have been yearning for being able to permanently alter the DNA, by inserting or deleting genes or specific pieces of DNA. The reason is that this process can be applied to agronomy, veterinary and human medicine. ”

“ For a specific disease, the prediction result will be limited by existing knowledge about the disease, including the number of known disease genes and their relationships within the existing data sources. We have used the concept of disease families in order to increase the number of known disease genes in each family. Some recent studies have considered relationships/similarities between diseases/phenotypes [29] and have utilized phenotype similarities in their gene prioritization approach [30] – [31] . We will investigate approaches to incorporate phenotype similarities into our framework. ”

“ In the disentanglement of the properties and interactions of these elementary factors, the science we must call to our aid is Physiological Chemistry. The relations of Genetics with the other branches of biology are close. Such work can only be conducted by those who have the good fortune to be able to count upon continual help and advice from specialists in the various branches of Zoology, Physiology, and Botany. ”

“ ESSENTIAL PREMISES The mechanism of heredity lies in a single germ cell carrying the character-determining chromosomes which consist of organized chains of genes. In the character and organization of these genes in the fertilized cell we find the complete "blueprint" for the future individual in so far as it is to be determined by heredity. In the twenty-four pairs of chromosomes in the fertilized human germ cell we find the long and diversified heritage of each parent represented through the union of the sperm and the ovum. ”

“ If there are inheritance units, such as determiners or genes, as practically all students of heredity maintain, they must be contained in the germ cells, and it becomes one of the fundamental problems of biology to find out where and what these units are. ”

“ Inheritance is of definite traits, such as eye color, height, musical genius, high or low resistance to a germ disease, for example, tuberculosis. Research work in genetics is at the present time especially concerned with discovering what are the unit characters and how each is transmitted.
Special cells, called germ cells, are the carriers of heredity; these contain the determining factors for physical and mental characteristics. These, like all the other cells of the body, are microscopic in size. The body of the individual is the temple in which the sacred cells of the race are protected. ”

“ Experimental embryology, histology, regeneration, comparative physiology, neurology, cytology, and heredity have in recent years successfully adopted an experimental aspect and have made significant progress thereby. Biology has now taken its place beside chemistry and physics as an experimental science.
The latest great advance in biology has been in the field of heredity. The rediscovery of the Mendelian principles of heredity in 1900 brought to light the most important generalization in biology in recent times. The new science of genetics is essentially the experimental study of heredity. ”

“ This hereditary substance is the germ-plasm. It is the living, vital substance of organisms that takes part in the development of new generations.
Naturalists are agreed on this point, that the more complex animals and plants have been derived from the simpler ones; and, this being accepted, the attention should be fixed on the nature of the connection between generations during their long line of descent. In the reproduction of single-celled organisms, the substance of the entire body is divided during the transmission of life, and the problem both of heredity and origin is relatively simple. ”

“ To the student of genetics, man, like any other animal, is material for working out the manner in which characters, whether physical or mental, are transmitted from one generation to the next. Viewed in this way he must be regarded as unpromising, not only from the small size of his families, the time consumed in their production, and the long period of immaturity, but also because full experimental control is here out of the question. ”