robbins

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
• Human genetic disorders can be broadly classified into three
categories.
1. Disorders related to mutations in single genes with large effects (mendelian
disorders)
2. Chromosomal disorders.
3. Complex multigenic disorders.
4. 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

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

13. POINT MUTATIONS

14. 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.

17. MISSENSE MUTATION

25. FRAMESHIFT MUTATIONS
Addition or removal of one or
more Nucleotides, resulting in a
shift of the reading sequence

27. 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.

28. Mutations Within Noncoding Sequences

29. 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.

30. Alterations In Noncoding RNAs.

31. Trinucleotide-repeat Mutations.

32. 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.

33. Thank you