Principles of genetics by Gregor Johann Mendel are discussed in this article.Being a Doctor and student you must understand these basic genetics principles.As you know Mendal is called the father of genetics.
It is a convenient if misleading abstraction consider that all diseases of man are due either to the action of environmental agents or to hereditary influences. This simplistic view has been nurtured by innumerable studies that purport to relegate a disease into one or the other category. It is more correct, however, as well as more rewarding, to consider that both environmental and hereditary influences play a role in the etiology of disease. In some conditions genetic influences are clearly decisive, whereas in others the disease appears to be independent of the genetic constitution of the patient. In the majority of diseases, both genetic and environmental factors play a detectable influential role.
The science of human genetics is concerned primarily with the recognition of hereditary variations in man. Most of these variations are not harmful; indeed they are beneficial, for they confer on the species the capacity to adapt to and ever-changing environment. But when these variations are associated with clinical disease they come within the realm of the physician. Since medical genetics is an applied science, certain general genetic principles will be discussed before considering in detail the direct application of genetics to clinical medicine.
How To Define The Concept of Mendel’s Principle And His Principles of Genetics
Following the establishment of the principle of genetic transmission by Gregor Mendel, Johannsen, in 1909, introduced the word gene to denote a unit’ of heredity. A structural gene is now defined, operationally, as a functional unit of inheritance situated on a chromosome and responsible for the synthesis of a specific polypeptide. It has been estimated that there are probably no less than 100,000 genes in man. The chemical nature of a gene was unrecognized until 1944, when a soluble extract derived from pneumococcus of one genotype was found to effect a stable heritable change when added to a growing culture of pneumococcus of another genotype.
The prompt definition of the transforming substance in the exact as deoxyribonucleic acid (DNA) launched the present era of molecular biology. The genetic information encoded in the DNA that determines polypeptide structure is transcribed through the synthesis of in another macromolecule, ribonucleic acid (RNA).Part of this RNA is termed messenger RNA (m RNA) and the linear amino acid sequences in the polypeptide chain are precisely determined by the linear sequences of the coding units (codons) in the RNA. These relationships are often referred HI flue tie central dogma of molecular biology, and can be depicted schematically.
Deoxyribonucleic Acid is constructed from thee essential components.the pentose sugar 2 deoxy d ribose, phosphoric acid,which confers on DNA its acidic properties, and nitrogenous bases.
Two polynucleotide chains are twisted together to form a double helix. The two chains are held together with hydrogen bonds between the bases which face inward forming the core, and the phosphate-sugar groups form the backbone. The most important feature of the model is the physical-chemical requirement for specific base pairing. Adenine must always pair with thymine (A-T), and guanine with cytosine (G-C). The result of this pairing leads to a precise complementary relationship between the bases on the two chains. Thus, if part of the base sequence of one chain were TGCC the corresponding portion of the complementary strand would read ACGG.
Replication of DNA.
One of the chief attractions of the Watson-Crick model for DNA is a built-in system for self-replication. As the double helix unwinds, each strand acts as a template for the synthesis of a new strand catalyzed by the enzyme DNA polymerase. The replication has been termed semiconservative since one of each parental strand is conserved in the next generation when it will pair with its newly synthesized complementary partner.
Ribonucleic acid differs from deoxyribonucleic acid in three important ways. (1) The sugar D-ribose replaces the 2-deoxyribose of DNA. (2) The pyrimidine base uracil replaces the thymine of DNA. (3) RNA is a single-stranded polymer in contrast to double-stranded DNA.
Acid (m RNA). Messenger RNA is synthesized directly on the DNA template. Adenine pairs with uracil, guanine with cytosine. and single-stranded m RNA is formed. The. transcription of one of the strands of DNA to form RNA is catalyzed by the enzyme RNA polymerase (transcriptase). Thus, single-stranded RNA carries into the cytoplasm the genetic information is encoded in nuclear DNA in the form of a base sequence complementary to that of DNA. In bacteria, m RNA has a half-life of about two minutes, and it has been calculated that during this time 10 to 20 molecules of protein can be synthesized. In cells of higher organisms the messenger appears to be much more stable, and may remain functional for two to three days and synthesis several thousand molecules.
More than 80 percent of Cellular RNA is found in small cytoplasmic particles,closely associated with the endoplasmic reticulum,called ribosomes.These ribosomes particles are the protein synthetic machinery of the cell.Mammalian ribosomes have a diameter of approximately 200 A and a sedimentation coefficient of 80S, and dissociate into 60S and 40S sub units in low concentrations of magnesium.
Because most proteins normally contain 20 different amino acids and DNA has only four different nucleotide bases,it is evident that more than one base is required to prescribe for a particular amino acid. It is now know that three bases (a codon) are needed to code for each amino acid, and that the code is overlapping. Thus,a gene with 1500 nucleotide pairs would rf the sequence of a polypeptide chain consisting of 500 amino acids. Since the four-letter code is triplet in nature, there would be 64(4 <4 x4) possible codons, of which 61 have been shown to code Sac one of the 20 amino acids.
Three codons chain terminating codons) represent signals that flute polypeptide chain is completed, and two codons (chain-initiating codons) are signals for the action of polypeptide synthesis as well as for due insertion of amino acids. The genetic code is said to be universal in the sense that all plant and animals species probably use the same genetic code and degenerate because certain amine acid can be specified by more than one triplet.
Certain acridine-induced mutants in bacteriophage insert an extra nucleotide base into the and the reading frame becomes altered distal ts» the point of insertion of the new base leading to a disruption of normal protein synthesis. The correct reading frame of the code can be restored iii» a deletion of another base distal to the insertion.This model makes the prediction that a double mutant, consisting of an insertion followed by in deletion, will result in a polypeptide chain altered amino acid sequence between the the mutations. If the segment of DNA between the two mutations is short, and does not code for amino acids vital for functional specificity, a protein with normal or nearly normal function may be produced.
Structural and Control Genes.
The most extensive understanding of genetic regulatory, mechanisms stemmed from the investigations of jacob Monod, and their collaborators on the b galactosidase enzyme system in Escherichia coli. These studies have led to the formulation of new of regulation in bacteria according to hierarchy of control genes and structural genes has been established. Thus, whereas certain genes (structural genes) are responsible for the actual synthesis of specific protein and enzymes and contain the DNA code which specifies their amino acid sequences, other genes are responsible for the regulation of their production.
A dramatic example of a structural gene mutation in man was most clearly demonstrated Ingram reported in 1956 that sickle-cell hemoglobin differed from normal differed from normal hemoglobin in a single amino acid substitution. During the subsequent of 15 years a considerable number structural mutants have been identified in man many instances the precise amino acid substitution disclosed. The question of whether there are mutations in man who affect the protein such that a small amount of the normal structural protein is formed is less easy to document. Although many of the hereditary diseases studied by Garrod are characterized by synthesis of a decreased quantity of an enzyme of apparently normal structure, rigorous structural studies have not been performed.
Though almost all control gene mutations in bacteria lead to a greatly decreased synthesis, or absence, of a particular protein, it is quite possible for a structural gene mutation to have so altered the code that no protein is synthesized, or that protein synthesized has become immunologically, enzymatically, and chemically unrecognizable. Thus, although the distribution between control gene mutations and structural mutation can be resolved in microorganisms by tracing the mutation to a locus within or outside the structural gene, techniques for a similar analysis in man are not yet available.
It can be assumed that in man the regulation of gene function is far more complex than in bacteria,, and the application of the Jacob- Monod model is undoubtedly a misleading oversimplification. It seems likely that in certain inherited diseases the primary biochemical abnormality resides in a decreased or defective synthesis of messenger RNA, or may be due to ambiguities :n the reading of the messenger on the ribosome. The primary abnormality in thalassemia has been ascribed to defective synthesis of m RNA. A disturbance in the regulatory mechanism of the level : f translation cannot be excluded.