Inherited Diseases and Genetic Disorders in Human Beings

Dr.P. Pushpangadan


In 1943, Oswald Avery, along with co-workers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle, supporting Griffith's suggestion (Avery–MacLeod–McCarty experiment). DNA's role in heredity was confirmed in 1952 when Alfred Hershey and Martha Chase in the Hershey–Chase experiment showed that DNA is the genetic material of the enterobacteria phage. In Eukaryotes whose cells have a nucleus enclosed within membranes, unlike prokaryotes (Bacteria and Archaea), which have no membrane-bound organelles. Eukaryotes belong to the domain Eukaryota or Eukarya. Animals and plants are the most familiar eukaryotes. Each gamete has just one set of chromosomes, each a unique mix of the corresponding pair of parental chromosomes resulting from genetic recombination during meiosis. Eukaryotes represent a tiny minority of all living things. However, due to their generally much larger size, their collective worldwide biomass is estimated to be about equal to that of prokaryotes. Eukaryotes evolved approximately 1.6–2.1 billion years ago.


In 1951, Francis Crick started working with James Watson at the Cavendish Laboratory within the University of Cambridge. In 1953, Watson and Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature. Their double-helix, molecular model of DNA was then based on one X-ray diffraction image. For a non-technical introduction to the topic, see Introduction to genetics. For other uses, see DNA.  DNA is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids; alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life. The model building efforts were guided by X-ray diffraction data acquired by Raymond Gosling, who was a post-graduate student of Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials. The two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes genetic information. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation. In 1962, Watson and Crick got Nobel Prize for the same.


DNA, short for deoxyribonucleic acid, is a universal carrier of hereditary information. In all life forms-viruses, bacteria, fungi, plants and animals –it carries important instructions for the design of the organism.  And not only does it carry information- it is also a molecule designed so that it may be accurately copied to the next generation. DNA is built from simple unit, referred to as nucleotides that are joined to form very long molecules. Each nucleotide contains any of four different nitrogenous bases: adenine, thymine, cytosine, or guanine, abbreviated A, T, C and G, respectively. It is the sequence of these bases that forms the actual genetic message. The complementary nitrogenous bases are divided into two groups, pyrimidines and purines. In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine. The two DNA strands are also known as polynucleotides as they are composed of simpler monomeric units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases (cytosine, guanine, adenine or thymine), a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules (A with T and C with G), with hydrogen bonds to make double-stranded DNA.


Human Genome


The human genome is the entire "treasury of human inheritance." The sequence of the human genome obtained by the Human Genome Project, completed in April 2003, provides the first holistic view of our genetic heritage. The 46 human chromosomes (22 pairs of autosomal chromosomes and 2 sex chromosomes) between them house almost 3 billion base pairs of DNA that contains about 20,500 protein-coding genes. The coding regions make up less than 5% of the genome (the function of all the remaining DNA is not clear) and some chromosomes have a higher density of genes than others.


Genes and Heredity


Heredity is the passing of genes from one generation to the next. You inherit your parents' genes. Heredity helps to make you the person you are today: short or tall, with black hair or blond, with brown eyes or blue. Other genetic diseases like Sickle cell anemia, Cystic fibrosis, Lysosomal acid lipase deficiency, Glycogenstorage diseases, Galactosemia, most of the cancers etc are examples of genetic disorders.                 


We refer to the complete genetic material of an organism as its genome. The human genome is an astounding three billion letters. An important milestone was reached in biomedical research in 2001 when, for the first time, a draft of the human genome was presented and the complete sequence of letters could be read. Consider the whole genome printed as a physical book. You would need in the order of 5,00,000 pages like this to cover the full human genome. That would correspond to more than 1600 books, each with 300 pages.


DNA Nanotechnology


DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties. DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based and using the DNA origami method) and three-dimensional structures in the shapes of polyhedra. Nanomechanical devices and algorithmic self-assembly have also been demonstrated, and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.


What is the general organization of the human genome and what elements are quantitatively or functionally important? What is the structure of genes, and what is their environment?. For instance we learn that the human genome contains not only protein –coding genes but a lot of noncoding material, including a huge number of repetitive elements. It contains the genetic information that allows all forms of life to function, grow and reproduce. However, it is unclear how long in the 4-billion-yearhistory of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material. RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes Bioinformatics involves the development of techniques to store, data mine, search and manipulate biological data, including DNA nucleic acid sequence data. These have led to widely applied advances in computer science, especially string searching algorithms, machine learning, and database theory. String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides.


Both strands of double-stranded DNA store the same biological information. This information is replicated as and when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences.


Genetic Disorder


A genetic disorder is a genetic problem caused by one or more abnormalities formed in the genome. Mitotic /Meiotic abnormalities causing irregular pattern of chromosome segregation resulting in addition of a chromosome or Mutation in the chromosome and other abnormalities. Most genetic disorders are quite rare and affect one person in every several thousands or millions. Genetic disorders may be hereditary, meaning that they are passed down from the parents' genes. In other genetic disorders, defects may be caused by new mutations or changes to the DNA. In such cases, the defect will only be passed down if it occurs in the germline. The case of Mr. Joseph Carey Merrick (5 August 1862 – 11 April 1890) English man had a severe deformities He was first exhibited at a freak show as the "Elephant Man", and then went to live at the London was reported to be a genetic disorder caused by an abnormality to gereric in the genetic makeup of an individual. At that time there was no knowledge of genetic disorders.


Sickle Cell Anemia


Sickle cell anemia is an inherited form of anemia — a condition in which there aren't enough healthy red blood cells to carry adequate oxygen throughout your body. ... In sickle cell anemia, the red blood cells become rigid and sticky and are shaped like sickles or crescent moons. Sickle cell disease is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disorder have atypical hemoglobin molecules called hemoglobin S, which can distort red blood cells into a sickle, or crescent, shape.


Sickle cell anemia is caused by a mutation in the gene that tells your body to make the red, iron-rich compound that gives blood its red color (hemoglobin). Hemoglobin allows red blood cells to carry oxygen from your lungs to all parts of your body. In sickle cell anemia, the abnormal hemoglobin causes red blood cells to become rigid, sticky and misshapen.


The sickle cell gene is passed from generation to generation in a pattern of inheritance called autosomal recessive inheritance. This means that both the mother and the father must pass on the defective form of the gene for a child to be affected.


Gene therapy


Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient's cells instead of using drugs or surgery. Gene therapy was conceptualized in 1972, by authors who urged caution before commencing human gene therapy studies.


The first attempt, an unsuccessful one, at gene therapy (as well as the first case of medical transfer of foreign genes into humans not counting organ transplantation) was performed by Martin Cline on 10 July 1980. Cline claimed that one of the genes in his patients was active six months later, though he never published this data or had it verified and even if he is correct, it's unlikely it produced any significant beneficial effects treating beta-thalassemia. DNA must be administered, reach the damaged cells, enter the cell and either express or disrupt a protein. Multiple delivery techniques have been explored. The initial approach incorporated DNA into an engineered virus to deliver the DNA into a chromosome. Naked DNA approaches have also been explored, especially in the context of vaccine development. Gene editing is a potential approach to alter the human genome to treat genetic diseases, viral diseases, and cancer. As of 2016 these approaches were still years from being medicine. Gene therapy is still in infancy.


In germ line gene therapy (GGT), germ cells (sperm or egg cells) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes all the organism's cells to contain the modified gene. The change is therefore heritable and passed on to later generations. Australia, Canada, Germany, Israel, Switzerland, and the Netherlands prohibit GGT for application in human beings, for technical and ethical reasons, including insufficient knowledge about possible risks to future generations and higher risks versus SCGT. The US has no federal controls specifically addressing human genetic modification (beyond FDA regulations for therapies in general).




The authors express their sincere thanks to Dr. Ashok K. Chauhan, Founder President, RBEF and Chairman, Amity Group of Institutions and also to Dr. Atul Chauhan, Chancellor, Amity University Uttar Pradesh, Noida and President, RBEF for providing necessary facilities and encouragement. The authors are also thankful to Mr. Arun S S for doing the typing work.




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