LEC.no.1 Human Genetics Structure of nucleic acids:DNA&RNA

LEC.1
Dr. Roaa S. Mahdi 24/11/2015

Human Genetics


Structure of nucleic acids:DNA&RNA

Nucleic acid is composed of a long polymer of individual molecules called nucleotides. Each nucleotide is composed of a nitrogenous base, a sugar molecule and a phosphate molecule.
The nitrogenous bases fall into two types, purines and pyrimidin, the purines include adenine and guanine; the pyrimidines include cytosine, thymine and uracil.
There are two different types of nucleic acid, ribonucleic acid (RNA), which contains the five carbon sugar ribose, and deoxyribonucleic acid (DNA), in which the hydroxyl group at the 2 position of the ribose sugar is replaced by a hydrogen (i.e. an oxygen molecule is lost, hence deoxy ).
DNA and RNA both contain the purine bases adenine and guanine and the pyrimidine cytosine, but thymine occurs only in DNA and uracil is found only in RNA.
RNA is present in the cytoplasm and in particularly high concentrations in the nucleolus of the nucleus. DNA is found mainly in the chromosomes.
The DNA molecule is composed of two chains of nucleotides arranged in a double helix. The backbone of each chain is formed by phosphodiester bonds between the 3 and 5 carbons of adjacent sugars, the two chains being held together by hydrogen bonds between the nitrogenous bases , which point in towards the center of the helix.



The chain end terminated by the 5 carbon atom of the sugar molecule is referred to as the 5 end,
and the end terminated by the 3 carbon atom is called the 3 end.
In the DNA duplex the 5 end of one strand is opposite the 3 end of the other,they have opposite orientation and are said to be antiparrellel.
The arrangement of the bases in the DNA molecule is not random. A purine in one chain always pairs with a pyrimidine in the other chain, with specific pairing of the base pairs: guanine in one chain always pairs with cytosine in the other chain, and adenine always pairs with thymine, so that this base pairing
forms complementary strand.
How genetic information is transmitted from one generation to the next
During nuclear division the two strands of the DNA double helix separate through the action of enzyme
DNA helicase, each DNA strand directing the synthesis of a complementary DNA strand through specific base pairing, resulting in two daughter DNA duplexes that are identical to the original parent molecule when cells divide, the genetic information is conserved and transmitted unchanged to each daughter cell ,this process is called replication.










Gene structure
The original concept of a gene as a continuous sequence of DNA coding for a protein , Human genome has approximately 25000 genes, which are the individual unit of heredity, that consist of coding regions called exons that encode the amino acids sequence of a protein and intervening segments called introns which are non coding regions whose DNA not represented in the finished protiens .The genes are organized into long segments of DNA, which, during cell division are compacted into intricate structures with proteins to form chromosomes.



Transcription

The process whereby genetic information is transmitted from DNA to RNA is called transcription.
The information stored in the genetic code is transmitted from the DNA of a gene to messenger RNA( mRNA), every base in the mRNA molecule is complementary to a corresponding base in the DNA of the gene, but with uracil replacing thymine in mRNA. mRNA is single stranded, being synthesized by the enzyme RNA polymerase, which adds the appropriate complementary ribonucleotide to the
3 end of the RNA chain.
RNA processing

Before the primary mRNA molecule leaves the nucleus it undergoes a number of modifications, or what is known as mRNA processing, this is involves splicing, capping and polyadenylation.
***mRNA splicing

After transcription, the non-coding introns in the primary mRNA are excised, and the non-contiguous coding exons are spliced together to form a shorter mature mRNA before its transportation to the ribosomes in the cytoplasm for translation, this process is known as mRNA splicing.
***5 capping

Shortly after transcription, the nascent mRNA is modified by the addition of a methylated guanine nucleotide to the 5 end of the molecule by an unusual 5 to 5 phosphodiester bond, the so-called 5 caping, the 5 cap is thought to facilitate transport of the mRNA to the cytoplasm and attachment to the ribosomes, as well as to protect the RNA transcript from degradation by endogenous cellular exonucleases .
***Polyadenylation

The cleavage of the 3 end of the mRNA molecule from the DNA involves the addition of approximately 200 adenylate residues ,this called polyadenylation .

Translation
Translation is the transmission of the genetic information from mRNA to protein, newly processed mRNA is transported from the nucleus to the cytoplasm, where it becomes associated with the ribosomes which are the site of protein synthesis. Ribosomes are made up of two different sized subunits, which consist of four different types of ribosomal RNA (rRNA) molecules and a large number of ribosomal specific proteins. Groups of ribosomes associated with the same molecule of mRNA are referred to as
polyribosomes or polysomes ,in the ribosomes, the mRNA forms the template for producing the specific sequence of amino acids of a particular polypeptide.
Post translation modification
Many proteins, before they attain their normal structure or functional activity , undergo post-translational modification, which can include chemical modification of amino-acid side-chains (e.g. hydroxylation, methylation), the addition of carbohydrate or lipid moieties (e.g. glycos-vlation) or proteolytic cleavage of polypeptides (e.g. the conversion of proinsulin to insulin).
Structure of chromosome
A chromosome is very much wider than the diameter of a DNA double helix. In addition, the amount
of DNA in the nucleus of each cell in humans means that the total length of DNA contained in the chromosomes, if fully extended, would be several meters long .
Under the electron microscope chromosomes can be seen to have a rounded and rather irregular morphology, however , most of our knowledge of chromosome structure has been gained using light microscopy and are best seen during cell division, when the chromosomes are maximally contracted and
the constituent genes can no longer be transcribed.
Each chromosome can be seen to consist of two identical strands known as chromatid , These chromatids can be seen to be joined at a primary constriction known as the centromere. Centromeres consist of several hundred kilobases of repetitive DNA and are responsible for the movement of chromosomes at cell division. The tip of each chromosome arm is known as the telomere, which play a crucial role in sealing the ends of chromosomes and maintaining their structural integrity.
Morphologically chromosomes are classified according to the position of the centromere. If this is located centrally, the chromosome is metacentric, if terminal it is acrocentric, and, if the centromere is in an intermediate position the chromosome is submeatcentric.


The mitochondria contain their own unique genome. The mitochondrial chromosome consist of a double-stranded circular piece of DNA, which contains 16,568 base pairs(bp) of DNA . All mitochondria are maternally derived because sperm do not usually carry mitochondria into fertilized eggs.
The mutation:
refers to permanent changes in the DNA, Those that affect germ cells are transmitted to the progeny and may give rise to inherited diseases. Mutations in somatic cells are not transmitted to the progeny but are important in the causation of cancers and some congenital malformation.
Types of mutations :

•Point mutation: result from substitutions of a single nucleotide base by a different base ,resulting in the replacement of one amino acid by another in the protein product, the best example of point mutation is sickle cell anaemia ,such mutations are sometimes called missense mutations. In contrast certain point mutations may change the an amino acid codon to a chain termination codon or stop codon, this type of mutations are called nonsense mutation which interrupt translation and the resultant protein is rapidly degraded.
• frame shift mutations: occurs when the insertion or deletion of one or two base pairs alters the reading frame of DNA strand.
• Trinucleotide repeat mutations: these mutations are characterized by amplifications of a sequences of 3 nucleotides , all affected sequences share the nucleotides guanine (G) and cytocine (C ), e.g: fragile X syndrome in which there are 200-4000 repeats of the sequence CGG with in a gene.