2. CHROMOSOME MUTATION Chromosomal Mutation Mutation involving a long segment of DNA. Involves Numerical abnormalities- number of chromosomes changes (represent about 60% of all chromosome abnormalities) or Structural abnormalities -structural changes occur in the chromosomes May involve the autosomes, the sex chromosomes or both simultaneously. Chromosome Mutation Chromosome structure become influenced by 1.Change in amount of genetic information in chromosome because of Deletion Duplication 2.Similar amount of genetic information but the materials are rearranged Inversion Translocation Chromosome Mutation contd Deletion Loss of chromosomal segment Duplication Repetition of chromosomal segment Inversion A change in the direction of the genetic material along a single chromosome Translocation A segment of one chromosome becomes attached to a different chromosome Simple translocation One way transfer Reciprocal translocation Two way transfer Duplications Insertion of an extra copy of a region of a chromosome into a neighboring position. Zygotes produced from gametes involving duplications are often viable and may or may not have any serious problems. Related to color vision conditions, many of which are quite subtle in effects e.g certain anemias involving abnormal hemoglobins called the thalassemias. Charcot-Marie-tooth Deletions Deletions result when a gene is mistakenly removed from a chromosome, as a result of unequal crossing over. Often zygotes produced by gametes involving deletions are not viable since they do not have the full compliment of genes. Cri-du-chat syndrome Partial deletion of the short arm of chromosome number 5, also called "5p monosomy" Inversions Inversions happen when a whole region of genes on a chromosome gets flipped around. 2 types of inversions. paracentric inversions the centromere is not included in the inversion. pericentric inversions, the centromere is involved in the inversion. Both these types of inversions lead to abnormalities in crossing over and meiosis resulting in some chromosomes which are not viable, while others are viable but have new combinations of genes. These sorts of inversions are thus important in reshuffling genes on a chromosome. Inversion mutation Normal gene GGTCTCCTCACGCCA CCAGAGGAGUGCGGU Codons Pro-Glu-Glu-Cys-Gly Amino acids Inversion mutation GGTCCTCTCACGCCA CCAGGAGAGUGCGGU Pro-Gly-Glu-Cys-Gly Inversion mutations, also, only affect a small part of the gene 2010 Paul Billiet ODWSODWS Translocations Movement of part of a chromosome to another part of the genome. May happen with the same chromosome. translocation is an intra-chromosome translocation. Other translocations involve transfer of a region of a chromosome to a non homologous chromosome. For example certain types of Down syndrome involve translocations between chromosome 14 and chromosome 21. This type of translocation between non homologous chromosomes is called an inter- chromosomal translocation. Transversion and Translocation Both of these usually cause no phenotypic changes Base substitution changes is in pair 2 types of changes Transition (within same group AT and GC) Transversion (between 2 groups) Transition vs Transversion GENOME MUTATION Patau syndrome (Trisomy 13) Changes in chromosome number Euploidy- a complete chromosomal set, specific to a given species Chromosome numbers can vary in 2 ways Polyploid An increase in the number of the complete sets of chromosome In animals and plants Aneuploid Abnormal number of chromosomes within a set Variations are less common Letter N represent a set of chromosome Diploid- 2N Triploid- 3N Tetraploid- 4N However, total number of chromosomes is not an exact multiple of a set (Aneuploidy) eg. A fly contains 9 chromosomes instead of 8 whereby it has three copies of chromosome 2. Thus it is called trisomy 2 or trisomic (2N + 1) Eg. A fly with 7 chromosomes are called monosomic (2N -1) Changes in chromosome number contd Monosomy Aneuploidy 2N ends up either with extra copies of homologous chromosomes or fewer than the normal diploid number. Happens when homologous chromosomes fail to segregate properly during meiosis (non disjunction). Monosomy (2n-1) in which the diploid individual has only one member of a certain homologous chromosome. The other common type of aneuploidy is called trisomy (2n+1) because the individual has three copies of the chromosome. Failure of chromosome to segregate Aneuploidy Trisomy 21 leads to Down syndrome, characterized by mental retardation and other abnormalities. Sex chromosomes examples are XYY males are normal but XXY males and XXXY males have a syndrome called Klinefelter syndrome. These males are often actually intersexed or hermaphroditic with partially developed sexual organs of both genders. These individuals are sterile and are often subjected to hormones and surgery to bring them into conformance with social gender roles. Edwards Trisomy 18 The XYY Jacobs syndrome men 47,XYY ; an extra copy of the Y chromosome Taller than average, but typically causes no unusual physical features. Most have normal sexual development and are able to father children. Associated with d risk of learning disabilities and delayed development of speech and language skills. Delayed development of motor skills (such as sitting and walking), weak muscle tone (hypotonia), hand tremors or other involuntary movements (motor tics), and behavioral and emotional difficulties are also possible. A small percentage of males with 47,XYY syndrome are diagnosed with autistic spectrum disorders, which are developmental conditions that affect communication and social interaction. The XYY Jacobs syndrome men Klinefelter syndrome XXY As XXY males enter puberty, they often don't make as much testosterone as other boys. Can lead to a taller, less muscular body, less facial and body hair, and broader hips than other boys. As teens, XXY males may have larger breasts, weaker bones, and a lower energy level than other boys. By adulthood, XXY males look similar to males without the condition, although they are often taller. They are also more likely than other men to have certain health problems, such as autoimmune disorders, breast cancer, vein diseases, osteoporosis, and tooth decay. XXY males can have normal sex lives, but they usually make little or no sperm. Between 95% and 99% of XXY males are infertile because their bodies don't make a lot of sperm. Polyploidy In contrast to animals, plants commonly exhibit polyploidy- having multiple sets of chromosomes 30-35% ferns and plants are polyploid Polyploid plants exhibit outstanding agricultural characteristics Often larger in size and more robust Polyploids Polyploids with odd number of chromosome are usually sterile This is detrimental but can confer desirable traits in agriculture such as seedless fruits and flowers Questions ??? Nabi Muhammad s.a.w pernah bersabda: "Andaikan kamu berbuat dosa hingga dosamu mencapai langit, kemudian kamu bertaubat, nescaya Allah s.w.t. memberi ampun kepada kamu" (Riwayat ibn Majah) Nabi Muhammad s.a.w pernah bersabda: "Bukanlah kemuliaan itu dengan memakai pakaian cantik dan bersegak tetapi ia adalah dengan ketenangan (sopan santun) dan merendah diri" (Riwayat Ad-Dailami) Causes of Mutation Factors that causes mutation 2 Factors that contribute to mutation Error in DNA replication. Damaging effects of mutagens CHEMICALS: Alkylating agents like nitrosoguanidine, nitrosamine, etc. RADIATIONS: X-rays, U.V.rays, etc. Error in replication Factors that causes mutation A.Chemical mutagens - used in research to study mutagenesis. There are 3 kinds of chemical mutagens. 1. Alkylating agents. Adds alkyl group, C n H (2n+1) Eg. formalin, nitrogen, mustard, and ethylene oxide (reacts with G changing it to bind with T). 2. Base analogs. Mimics a nitrogen base. Eg. AZT is a modified sugar that substitutes for T. Eg. 5 - bromouracil binds with A or G. 3. Intercalating agents. Inserts into DNA and pushes bases apart. Eg. AFLATOXIN - a chemical produced by peanut and grain molds. The mold is Aspergillus flavus (fungus). Factors that causes mutation contd B. Physical mutagens: 1. nonionizing radiation - Causes the formation of T= T dimers. UV 260 nm. 2. Ionizing radiation - damages DNA by causing the formation of free radicals leading to mutations. Eg. X-rays. Gamma rays from radioactive fallout penetrates the body. Alpha rays from inhaled dust containing radioactive fallout. 35 Possible effects of Mutagens DNA repair system 36 Photoreactivation Or Direct repair system Nucleotide excision repair system Mismatch repair system SOS repair system DNA REPAIR 37 DNA repair in a nut shell 38 39 PHOTOREACTIVATION /direct repair system Acts directly on damaged nucleotides, converting each one back to its original structure. Thymine dimerisation 40 EXCISION REPAIR SYSTEM It involves excision of a segment of the polynucleotide containing a damaged site, followed by resynthesis of the correct nucleotide sequence by a DNA Polymerase. 41 Excision repair system 42 MISMATCH REPAIR SYSTEM It corrects errors of replication, again by excising a stretch of single-stranded DNA containing the offending nucleotide and then repairing the resulting gap. 43 Methylation process 44 mismatch repair system 45 SOS REPAIR SYSTEM Save Our Souls The SOS repair system is an emergency measure for copying with a damaged genome. This is error prone. Save Our Souls The SOS repair system is an emergency measure for copying with a damaged genome. This is error prone. 46 SOS repair system 47 Conclusion A possible definition of mutation is therefore a deficiency in DNA repair 48 Nabi Muhammad s.a.w pernah bersabda: "Andaikan kamu berbuat dosa hingga dosamu mencapai langit, kemudian kamu bertaubat, nescaya Allah s.w.t. memberi ampun kepada kamu" (Riwayat ibn Majah)