Human genetics and research

Human genetics and research

We inherit some physical and biochemical from our parents and ancestors. Transmission of inherited characters or traits through generations is known as the heredity. Genetics is that branch of bio science, which deals with the study of the underlying principles of heredity it has been established that the genes of the chromosomes transmit the hereditary characters or traits. The expression of inherited characters is, however, modified by the environments in which an individual grows and develops.

Chromosomes

Chromosomes are deeply stained threadlike  structures within the nucleus  of each cell. Genes are borne by the chromosomes in linear series as parts  of specific DNA molecule. Individual chromosomes are visible under themicroscope only during cell division. During interphase of the cell, the nucleus contains a network of chromatin threads or granules but not individual chromosomes, because each choromosomes becomes uncoiled into long thin thread, which is beyond the resolution of the light microscope. But some chromosomes remain coiled at places and these are identified as chromatin granules in the interphase. The uncoiled portion of the chromosome is known as euchromatin which is genetically active; the coiled portion is called heterochrornatin which is genetically inert. During cell division, each chromosome is tightly coiled along its entire length and becomes shorter and thicker. Eventually  individual chromosomes are readily visible under the microscope. Therefore, the chromosomes are genetically inactive during cell division. All biochemical activities of chromosomes in the from of DNA replication, m RNA formation and protein synthesis take place during interphase which consists of three stages of the cell cycle Gap-1 synthesis, Gap-2 stages. DNA replication takes place in stages and covers a period of about 7 hours.  

Non-disjunction

The failure of a pair of chromosomes to separete at meiosis. allowing one daughter cell to have two chromosomes and the other to have none. Non-disjunction may take place in mitosis or meiosis, and it may involve sex chromosomes as well as autosomes. Autosomal non-disjunctionis less viable, particularly when it  affects large chromosomes.Turner's syndrome of female with 45, xo chromosomal constitution is possibly the only example of viable monosomic individual. If non-diajunction take place in first cleavage division of the zygota, than all cells are aneuploid and the individual shows rnosaicism with half of the total cells being trisomic and other half monnosomic. When non-disjunction occurs in meiosis l all four gametes are abnormal ( two, with 24 chromosomes, and two with 22 chromosomes. If it takes place in meiosis ll, two gametes, all cells of the organism derived from that zygota are aneuploid. Non-disjunction in gametogenesis is
sometimes observed in elderly females ( 40 years and above ). Possibly the primary ocyte which starts first meiotic division in prenatal life, completes the process just before ovulation after a prolonged interval of about 40 years or more.Delayed completes of first meiosis of oocyte might favour non-disjunction.

Sex chromatin or Barr bodies

During interphase, somatic cell of a normal female presents a heterochromatin plano convex body beneath the nuclear membrane this is known as sex chromatin or Barr body. Out of two x chromosomes in normal female, one of them is highly coiled and the other member highly uncoiled. The highly coiled  genetically inactive x chromosome forms the Barr body, which is plastered beneath the nuclear membrane. These bodies help in the nuclear sexing of the tissues. Barr bodies are easily found in those cells, which possess open faced nuclei. Usually Barr bodies are studied from the cells of busccal smear, or by observing ' drum stick ' bodies attached to the nuclei of polymorphonuclear leucocytes. The number of Barr bodies in a cell is equal to the total number of x chromosomes minus one. In a normal female with two x chromosomes the number of body is one.In triple x syndrome ( xxx )  the number is increased to two; in a female with Turner's syndrome
having only one x chromosome injnaia is detected as intensely fluorescent body (F-body) within the nucleus, when a buccal smear is stained with fluro chrome dye and examined under fluorescence microscope. Since this technique is costly and theside quickly deteriorates, it is usually not employed to study the sex chromatin status.

Chemical structure of chromosomes : On chemical analysis each chromosome is found to contain DNA, small amount of RNA histone and non-histone proteins, and metallic ions. DNA is the most essential and stable molecular constituent of chromosomes recent studies have revealed that each eukaryote chromosome contains a single continuous double-stranded DNA molecule. Mostof the DNA molecule exists in the chromosome as a highly coiled or folded structure. DNA in active state of transcription is most extended and becomes euchromatic; inactive DNA region remains highly coiled and becomes heterochromatic.Thedegree of coiling of DNA varies with the rate of protein synthesis in the different phases of cell cycle.

Chemical structure of DNA : DNA molecule is composed of two strands of polynucleotides arranged in a double helix. Each strands consists of a back bone of alternate pentose suger and phosphate molecule, and the two strands are held together by hydrogen bonds between the nitrogenoys bases, which are attached to the suger as side group and point towards the centre of the helix. The bases are of two kinds, purine and pyrimidine in the other strand always pairs with a pyrimidine in the other strand. Puring bases include adening (A) and guaning (G); pyrimidine bases include thymine (T) and cytosine (C). Base pairing is specific under normal condition (when in keto form)-adenine pairs with thymine having two hydrogen bonds and is
represented by A=T ; guaning pairs with cytosine by three hydrogen bonds and represented by G=C. This shows that during denaturation of DNA, separation of the two strands at A=T level is quicker than that of G=C level. However, when the bases are in enol from, adenine may pair with cytosine and guanine with thymine. This is basis of mutation of genes. The two strands of  DNA molecule are complementary to each other. If the base sequence of one strand can be formulated. Sequence of bases and  number of nucleotides of DNA are specific, and are different in different genes. Thus innumerable forms of DNA exist in the genes
and store diverse genetic information.

Genetic codes : Since bases of DNA or RNA  and amino acids of proteins are arranged in linear sequence, there must be some co-relation between nitrogenous bases and amino acids. DNA or RNA  presents four (4) bases, and primary structure of proteins is composed to twenty (20) amino acids. A sequence of three (3) bases of mRNA (and therefore of complementary DNA) codes for one amino acid. Since three consecutive bases are specific for one amino acid, the possible number of combinations of four bases taken three at a time would be 43 or 64. Such triplet of nucleotide basis is called a codon. Finally, all 64 codons are discovered specifying different amino acid. However,three codons such as UAG, UGA, and UAA do not code for any amino acid; hence these three are called non-sense or terminal codons and signal the termination of polypeptide chain.Three unpaired bases attached to one loop of mRNA as knwon as anti-codons which fit with the comple-mentary codons-of mRNA in a specific direction; as stated earlier, tRNA carries activated amino acid at one end of the chain.