Gene mutation

principle of genetics and genetic disorders

1. Gene mutation Lecture 6 Prepared by Samira Fattah Assis. Lec. College of health sciences-HMU

2. What is gene A gene is the basic physical and functional unit of heredity. Genes, which are made up of DNA, act as instructions to make molecules called proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The Human Genome Project has estimated that humans have between 20000 and 25000 genes.

3. Every person has two copies of each gene, one inherited from each parent . Most genes are the same in all people, but a small number of genes ( less than 1 percent of the total) are slightly different between people . Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features.

4. Mendel while explaining the results of his monohybrid and dihybrid crosses, first of all conceived of the genes as particulate units and referred them by various names such as hereditary factors or hereditary elements .

5. The Discovery of DNA DNA was first identified in 1869 by Friedrich Miescher , a Swiss biologist , removed the nuclei of pus cells and found that they contained a chemical material , he called nuclein , which , he separated the substance into a basic part (which we now know is DNA ) and an acidic part (a class of acidic proteins that bind to basic DNA ). Later the scientists realized that there are two types of nucleic acids : DNA (deoxyribonucleic acid ) and RNA (ribonucleic acid )

6. Nucleic Acids Deoxyribonucleic Acid (DNA) is the genetic material found in the cells of all living organisms. Nearly every cell (with a nucleus) in a person's body has the same DNA . Most DNA is located in the cell nucleus (where it is called nuclear DNA), but DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA ).

7. DNA and its close relative RNA are perhaps the most important molecules in biology. They contains the instructions that make every single living organism on the planet, and yet it is only in the past 50 years that we have begun to understand them. and they are called nucleic acids because they are weak acids , first found in the nuclei of cells. They are polymers, composed of monomers called nucleotides.

8. Nucleotide parts Nucleotides have three parts to them : 1-a phosphate group : which is negatively charged , and gives nucleic acids their acidic properties. 2-a pentose sugar , which has 5 carbon atoms in it . - the carbon atoms are numbered as shown to distinguish them from the carbon atoms in the base .

9. Nucleotide parts If carbon 2 has a hydroxyl group attached then the sugar is ribose, found in RNA. If the carbon 2 just has a hydrogen atom attached instead, then the sugar is deoxyribose , found in DNA.

10. 3-a nitrogenous base. There are five different bases, but they all contain the elements carbon, hydrogen , oxygen and nitrogen. The base thymine is found in DNA only and the base uraci l is found in RNA only, so there are only four different bases present at a time in one nucleic acid molecule.

11. Nitrogen Bases are: Adenine (A) Guanine (G) Cytosine (C ) Uracil ( U ) Thymine (T)

12. Nucleotide Polymerisation Nucleotides polymerise by forming bonds between carbon 3 of the sugar and an oxygen atom of the phosphate . The bases do not take part in the polymerisation , so there is a sugar-phosphate backbone with the bases extending off it. This means that the nucleotides can join together in any order along the chain.

13. Structure of DNA The three-dimensional structure of DNA was discovered in the 1950's by Watson and Crick . The main features of the structure are: • DNA is double-stranded, so there are two polynucleotide stands alongside each other.

14. • The strands are antiparallel , i.e. they run in opposite directions . • The two strands are wound round each other to form a double helix . • The two strands are joined together by hydrogen bonds between the bases . The bases therefore form base pairs, which are like rungs of a ladder.

15. The base pairs are specific . A only binds to T (and T with A ) and C only binds to G ( and G with C). These are called complementary base pairs . This means that whatever the sequence of bases along one strand, the sequence of bases on the other strand must be complementary to it .

16. Function of DNA DNA is the genetic material, and genes are made of DNA . Therefore DNA has two essential functions : replication and expression .

17. Replication means that the DNA, with all its genes,must be copied every time a cell divides . • Expression means that the genes on DNA must control characteristics.

18. A gene was traditionally defined as a factor that controls a particular characteristic (such as flower color ). but a much more precise definition is that a gene is a section of DNA that codes for a particular protein. Characteristics are controlled by genes through the proteins they code for.

19. Expression can be split into two parts : transcription ( making RNA ) and translation (making proteins ). • These two functions are summarized in this diagram ( called the central dogma of genetics ).

20. RNA RNA is a nucleic acid like DNA, but with 4 differences: 1-RNA has the sugar ribose instead of deoxyribose 2-RNA has the base uracil instead of thymine 3-RNA is usually single stranded 4-RNA is usually shorter than DNA

21. The Genetic Code The sequence of bases on DNA codes for the sequence of amino acids in proteins . But there are 20 different amino acids and only 4 different bases , so the bases are read in groups of 3 . This gives 43 or 64 combinations, more than enough to code for 20 amino acids.

22. A group of three bases coding for an amino acid is called a codon , and the meaning of each of the 64 codons is called the genetic code. The genetic code can be expressed as either RNA codons or DNA codons .

23. Mutation Mutation is the alteration of DNA sequence. whether it be in a small way by the alteration of a single base pair, or whether it be a gross event such as the gain or loss of an entire chromosome. How common are mutations ? Mutations occurs at a frequency of about 1 in every 1 billion base pairs Everybody has about 6 mutations in each cell in their body!

24. If we have that many mutations, why don’t we look weird? Mutations are not always seen. The affected gene may still function. Mutations may be harmful . Mutations may be beneficial . Mutations may have no effect on the organism .

25. How do mutations affect a population One consequence may be genetic disease. However , although in the short term mutation may seem to be a BAD THING , in the long term it is essential to our existence . Without mutation there could be no change and without change life cannot evolve. Some variations may help population to survive better

26. Somatic or germinal ? The first point to consider is where is the mutation occurring? Most of our cells are somatic cells and consequently most mutations are happening in somatic cells . Only mutations in gametes (egg & sperm) are passed onto offspring. That is not to say that somatic mutation is unimportant, cancer occurs as a direct consequence of somatic mutation.

27. Types of mutations Substitution A substitution is a mutation that exchanges one base for another (i.e., a change in a single "chemical letter" such as switching an A to a G). Such a substitution could change a codon to one that encodes a different amino acid and cause a small change in the protein produced.

28. For example ,  sickle cell anemia is caused by a substitution in the beta-hemoglobin gene, which alters a single amino acid in the protein produced .

29. 2. Insertion Insertions are mutations in which extra base pairs are inserted into a new place in the DNA .

30. E xample : Huntington's Disease (HD) is a brain disorder that affects a person's ability to think, talk, and move . -Normally , the coding region of this gene contains the DNA sequence "CAG" repeated again and again. The number of times this triplet is repeated varies from person to person, ranging from 10 to 26 times

31. 3. Deletion Deletions are mutations in which a section of DNA is lost, or deleted .

32. Example : Cystic fibrosis is a genetic disorder that affects the respiratory and digestive systems . -People with cystic fibrosis inherit a defective gene on chromosome 7 called  CFTR  (cystic fibrosis transmembrane conductance regulator)

33. 4. Frame-shift insertions and deletions can alter a gene so that its message is no longer correctly parsed . This usually generates truncated proteins that are as useless These changes are called frameshifts .

34. Example : Tay –Sachs disease (or   hexosaminidase  A deficiency )   is a rare   autosomal recessive genetic disorder . causes a progressive deterioration of  nerve cells  and of mental and physical abilities that begins around 7 months of age and usually results in death by the age of four . - caused by a genetic mutation in the   HEXA  gene on (human )  chromosome 15.