1 GENE MUTATION Flashcards
is a permanent alteration in the DNA
sequence of a gene.
Gene mutation
This change can affect the protein that the gene codes for,
potentially leading to a variety of consequences for the
organism.
Gene mutation
CLASSIFICATIONS OF GENE MUTATIONS
HEREDITARY MUTATIONS
ACQUIRED (OR SOMATIC) MUTATIONS
DE NOVO (NEW) MUTATIONS
MOSAICISM
Are inherited from a parent and are present throughout a
person’s life in virtually every cell in the body
Hereditary Mutations
HEREDITARY MUTATIONS is also called as
Germline Mutations
Fertilized egg cell receives DNA from both parents
Hereditary Mutations
Occur at some time during a person’s life
ACQUIRED (OR SOMATIC) MUTATIONS
Present only in certain cells, not in every cell in the body.
ACQUIRED (OR SOMATIC) MUTATIONS
ACQUIRED (OR SOMATIC) MUTATIONS is caused by
environmental factors such as UV radiation.
Acquired mutations in somatic cells
ACQUIRED (OR SOMATIC) MUTATIONS
Cannot be passed to the next generation
ACQUIRED (OR SOMATIC) MUTATIONS
Hereditary or somatic
DE NOVO (NEW) MUTATIONS
Genetic disorders in which an affected child has a
mutation in every cell in the body but the parents do not
DE NOVO (NEW) MUTATIONS
There is no family history of the disorder
DE NOVO (NEW) MUTATIONS
Somatic mutations that happen in a single cell early in
embryonic development
MOSAICISM
Not present in a parent’s egg or sperm cells, or in the
fertilized egg, but happen a bit later when the embryo
includes several cells.
MOSAICISM
May or may not cause health problems
MOSAICISM
CAUSES OF GENE MUTATION
ERRORS IN DNA REPLICATION
ERRORS IN DNA RECOMBINATION
CHEMICAL DAMAGE TO DNA
RADIATION
DNA polymerase will incorporate a non-complementary
base into the daughter strand
ERRORS IN DNA REPLICATION
The mis-incorporated base would lead to a mutation
ERRORS IN DNA REPLICATION
Very rare as the exonuclease functions as a proofreading
ERRORS IN DNA REPLICATION
DNA often rearranges itself by a process called
recombination which proceeds via a variety of
mechanisms
ERRORS IN DNA RECOMBINATION
DNA is lost during replication leading to a mutation
ERRORS IN DNA RECOMBINATION
Chemical mutagens, some exogenous, some man-made,
some environmental, are capable of damaging DNA.
CHEMICAL DAMAGE TO DNA
Chemical mutagens, some exogenous, some man-made,
some environmental, are capable of damaging DNA.
CHEMICAL DAMAGE TO DNA
gamma rays, uv
RADIATION
Many chemotherapeutic drugs are intercalating agent
drugs that function by damaging DNA.
chemical damage to dna
TYPES OF GENE MUTATION
POINT MUTATION
CHROMOSOMAL MUTATION
COPY NUMBER VARIATION
SOMATIC MUTATION
TYPES OF POINT MUTATIONS
Single Mutation
Neutral Mutation
Missense Mutation
Nonsense Mutation
Single base modification
POINT MUTATION
Type of mutation that causes a single nucleotide base
substitution, insertion, or deletion of the genetic material,
DNA or RNA.
POINT MUTATION
Frameshift mutation indicates the addition or deletion of a
base pair.
POINT MUTATION
(TYPE OF POINT MUTATION)
Single-base alteration with no
significant change in the amino acid sequence
Single Mutation
(TYPE OF POINT MUTATION)
Single-base change producing a
different amino acid with a similar function.
Neutral Mutation
(TYPE OF POINT MUTATION)
Single-base change resulting in
a different amino acid with altered function.
Missense Mutation
(TYPE OF POINT MUTATION)
Single-base change leading to
a premature stop codon.
Nonsense Mutation
A mutation involving a long segment of DNA
CHROMOSOMAL MUTATION
These mutations can involve deletions, insertions, or
inversions of sections of DNA
CHROMOSOMAL MUTATION
CHROMOSOMAL MUTATION is also Also referred to as a
Chromosomal Arrangement
Genome are repeated and the number of repeats in the
genome varies between individuals in the human
population
COPY NUMBER VARIATION
Genetic alteration acquired by a cell that can be passed to
the progeny of the mutated cell in the course of cell
division.
SOMATIC MUTATION
_________ differ from germline mutations
Somatic mutations
Autosomal recessive genetic condition causing severe
lung damage and nutritional deficiencies
CYSTIC FIBROSIS
CYSTIC FIBROSIS is mainly caused by
mutations in both alleles of the CFTR
gene, leading to loss of function.
regulates chloride transport, resulting in thick and
sticky mucus, affecting respiratory function.
CFTR
IMPACT OF CFTR MUTATION
Dysregulation of chloride, sodium, and water transport
leads to increased salt concentration in sweat.
Over 2,000 CFTR mutations are linked to cystic fibrosis,
with the most common being a 3-bp deletion at position
508.
Autosomal dominant genetic condition leading to
significantly elevated LDL-cholesterol levels and increased
risk of premature cardiovascular disease.
FAMILIAL HYPERCHOLESTEROLEMIA (FH)
Can manifest as homozygous or heterozygous FH, with
homozygous FH causing a severe LDL-C level phenotype
FAMILIAL HYPERCHOLESTEROLEMIA (FH)
CAUSES OF FH
Mainly attributed to genetic mutations in the LDLR gene,
which encodes the LDL receptor.
Other causes include mutation in the APOB gene
(apolipoprotein B-100 gene), gain of function (GOF)
mutation in the PCSK9 gene, and loss of function (LOF)
mutation in the LDLRAP1 gene.
X-linked recessive genetic disorder resulting from a
deficiency in coagulation factor VIII (FVIII) encoded by the
F8 gene.
HEMOPHILIA A
Mutations associated with ______ include deletion,
duplication, insertion, insertion/deletion, inversion, and
substitution, with about 40% of cases caused by
inversions.
hemophilia A
CLASSIFICATION AND SYMPTOMS OF HEMOPHELIA A
● Hemophilia A can be categorized as severe, moderate, or
mild based on FVIII coagulant activity levels in the plasma
● Patients experience prolonged bleeding, delayed blood
clotting after injury, renewed or spontaneous bleeding,
which can be life-threatening.
● Joint bleeding can lead to arthropathy, impacting mobility,
and quality of life.
A heterogenous group of diseases characterized by
anemia and the presence of ring sideroblasts in the bone
marrow.
CONGENITAL SIDEROBLASTIC ANEMIA (CSA)
While primarily congenital, cases of acquired forms have
also been reported.
CONGENITAL SIDEROBLASTIC ANEMIA (CSA)
GENETIC BASES AND MUTATIONS
● The congenital form is often X-linked and linked to
mutations in genes related to heme biosynthesis,
iron-sulfur cluster biosynthesis, and mitochondrial protein
synthesis.
● Mutations in the erythroid-specific delta-aminolevulinic
synthase (ALAS2) gene, crucial for heme biosynthesis,
are a common cause of CSA.
● Mutations leading to decreased ALAS2 activity contribute
to CSA, while increased activity may result in X-linked
erythropoietic protoporphyria.
Hematologic disorder characterized by increased iron
absorption and excessive iron storage in various organs.
HEREDITARY HEMOCHROMATOSIS
HEREDITARY HEMOCHROMATOSIS
Iron deposition commonly seen in the liver, heart, joints,
pituitary gland, and pancreas
● Unaffected individuals absorb 1 to 2 mg of iron per day,
while those with hemochromatosis can absorb up to 30 g
daily.
● Excess iron absorption leads to iron overload and storage
issues in multiple issues.
IRON ABSORPTION AND STORAGE
Unaffected individuals absorb___ of iron per day,
while those with hemochromatosis can absorb up to ___
daily.
1 to 2 mg; 30 g
GENETIC BASIS AND MUTATIONS
Mutations in the HFE gene, encoding the β₂-
microglobulin-associated protein, are commonly
associated with hereditary hemochromatosis.
● Varying phenotypic expression has linked
hemochromatosis to other genes related to hereditary
anemia.
TYPES OF HEREDITARY HEMOCHROMATOSIS
Type 1
Type 2A, 2B, 3 & 4
(TYPE OF HEREDITARY HEMOCHROMATOSIS)
Classic form associated with variations in the HFE
gene.
Type 1
(TYPE OF HEREDITARY HEMOCHROMATOSIS)
Related to genes such as TfR2,
HJV, HAMP , and ferroportin 1, respectively
Type 2A, 2B, 3, and 4
MISSENSE MUTATIONS IN HFE GENE
o C2B2Y mutation: Cysteine-to-tyrosine substitution
disrupting disulfide bridges
o H63D mutation: Aspartic acid to-histidine
conversion.
o S65C mutation: Serine-to-cysteine conversion
leading to milder forms of hemochromatosis.
Anemia characterized by sickle-shaped red blood cells
due to a mutation in the protein globin
SICKLE CELL ANEMIA
Disorder characterized by an extra copy of chromosome
21 or partial duplication of its long-arm region (q22.1 to
22.3).
DOWN SYNDROME
Female chromosomal abnormality characterized by partial
or complete absence of an X chromosome (monosomy X)
in some or all cells.
TURNER SYNDROME
DETECTION OF GENE MUTATIONS
Biochemical Methods
○ Enzyme Immunoassays
○ Immunohistochemistry
○ High-Performance Liquid Chromatography
(HPLC)
○ Gas Chromatography
○ Mass Spectrometry
