Mutation , its types andprinciples relating to the effects of gene mutation. (genetics).pptx

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1. Mutation Dr. Al-Farah M. Phil (Pathology), PhD Scholar Asst. Professor Dept. of Pathology

2. Learning objectives Define Mutation. Briefly discuss principles relating to the effects of gene mutation. Distinguish between types of mutations in the coding and non-coding regions of genes.

3. Terminology Hereditary = derived from parents Familial = transmitted in the gametes through generations Congenital = present at birth (not always genetically determined - e.g., Congenital syphilis, toxoplasmosis) ! Not all genetical diseases are congenital - e.g., Huntington disease - 3rd to 4th decade of life

4. Introduction H uman genetic disorders can be broadly classified into three categories . Disorders related to mutations in single genes with large effects (mendelian disorders ) Chromosomal disorders. Complex multigenic disorders. Single-gene disorders with nonclassic patterns of inheritance.

5. Introduction 1. Mendelian disorders single-gene mutation of large effect Usually follow the classic Mendelian pattern of inheritance and are also referred to as Mendelian disorders - uncommon conditions (storage diseases, inborn errors of metabolism) associated with high penetrance. - usually hereditary and familial 2. Diseases with multifactorial (polygenic) inheritance - defects of multiple genes with small effect + environmental influences - some very common diseases (arterial hypertension, diabetes mellitus) 3. Cytogenetic disorders numeric or structural abnormalities of chromosomes - uncommon but associated with high penetrance.

6. Mutations Mutation is a permanent change in the nucleotide sequence of DNA that makes up a gene . Mutations range in size from one DNA base to a whole chromosome change. Gene mutations occur in two ways : They can be inherited from a parent ( hereditary mutations or germline mutations ) or Acquired during a person’s lifetime and occur in the DNA of individual cells ( acquired or sporadic mutations ).

7. Mutations: Causes Exposure to mutagenic agents (Mutagens) Errors in DNA replication Errors in DNA repair

8. Mutations: Outcomes Negative Effects- Change in DNA sequence leads to wrong protein produced = DISORDER NO Effect- JUNK DNA- does not code for anything Positive Effects- promotes characteristics that allow better survival = EVOLUTION

9. Mutations can be grouped according to Their origin, The cell type Effect on function

10. Types of mutation 1. Point mutations ( Base-pair substitutions) Silent mutation Missense mutation Nonsense mutation 2. Frameshift Mutations Insertion deletion

11. Point mutations

12. Silent mutation Mutations in which nucleotide changes do not alter the amino acid sequence of the protein. They occur in the coding region but do not result in a change in the final protein product.

13. MISSENSE Mutation

14. Frameshift Mutations Addition or removal of one or more Nucleotides , resulting in a shift of the reading sequence

15. Mutations Within Noncoding Sequences Not all changes in noncoding DNA have an impact on health, but those that alter the pattern of a critical protein can disrupt normal development or cause a health problem. Noncoding region of DNA play a role in the control of gene activity Determine when and where certain genes are turned on or off Important for protein assembly. By altering one of these regions, mutation in noncoding DNA can turn on a gene and cause a protein to be produced in the wrong place or at the wrong time. Alternatively, a variant can reduce or eliminate the production of an important protein when it is needed.

16. Mutations Within Noncoding Sequences

17. Alterations in protein-coding genes other than mutations . In addition to alterations in DNA sequence, coding genes also can undergo structural variations, such as copy number changes— amplifications or deletions —or translocations that result in aberrant gain or loss of protein function. EXAMPLE: Philadelphia chromosome—translocation t(9;22) between the BCR and ABL genes in chronic myeloid leukemia (Chapter 13)—is a classic example.

18. Alterations In Noncoding RNAs.

19. Trinucleotide-repeat Mutations.

20. Single-gene Disorders With Nonclassic Patterns Of Inheritance. Diseases within this group are caused by mutations in single genes, but they do not follow the Mendelian pattern of inheritance. This group includes disorders resulting from Triplet-repeat mutations Mutations in mitochondrial DNA ( mtdna ), Transmission influenced by genomic imprinting or gonadal mosaicism.

21. Thank you