8/22/2019 Mutation Note
1/16
http://matriculation-biology.blogspot.com
MUTATION(4 hour)
Retold by:
Amran Md Said,Matriculation College of Pahang.
Objective. At the end of this topic, students should be able to:
Explain mutation Classify mutation state types of mutation define mutagen state types of mutagen explain gene/point mutation classify gene mutation describe base substitution as point mutation eng. Sickle cell anemia explain frameshift mutation describe base insertion as a frameshift mutation describe base deletion as a frameshif mutation explain chromosomal mutation
classify chromosomal mutation explain chromosomal aberration (structural changes) state and describe type of chromosomal aberration explain alteration of chromosome number state the types of the alteration explain aneuploidy describe the cause and the affect aneuploidy explain autosomal abnormalities and their effects explain sex chromosomal abnormalities explain euploidy explain polyploidy
What is mutation?
A mutation is a change in the amount, arrangement or structure of the DNA of an organism.
Mutations produce sudden and distinct differences between individuals cause alternation ofchromosome.
Alteration of chromosome number or structure cause some genetic disorders such as Sickle CellAnemia and Down Syndrome
Mutation can occurring in gamete cells or somatic cells.
i) gamete cellsare inherited, It passed to subsequent generations as part of the hereditary endowment of thegames derived from that cell.
ii) somatic cells
can only be inherited by daughter cells produced by mitosis.
8/22/2019 Mutation Note
2/16
http://matriculation-biology.blogspot.com
A mutant is an individual or new genetic character arising or resulting from an instance of mutation theblue lobsteris an example of a mutant.
Type of mutationi) spontaneous mutation
- Mistakes happen spontaneously during DNA replication, repair and recombination- eg. nondisjunction
ii) induced mutation- Organism exposed to mutagen
What is mutagen ?
a mutagen (Latin, literally origin of change) is a physical or chemical agent that changes the geneticmaterial
Operate either by causing changes in the DNA of the genes or by causing chromosome damage type of mutagen
i) Physical agentUltraviolet rayIonizing radiation (X-ray, gamma ray, alpha particles, neutron and electron)
ii) Chemical agenteg. Colchicine (usually to treat rheumatic complaints, especially gout)Ethidium bromide (is an intercalating agent commonly used as a fluorescent tag in laboratories for
techniques such as agarose gel electrophoresis)
CLASSIFICATION OF MUTATION:
Classify of mutationi) gene / point mutationii) chromosomal mutation
GENE MUTATION (POINT MUTATION)GENE MUTATION (POINT MUTATION)
Producing alterations in the sequence of DNA nucleotide. involve only one or a few base pair in the coding sequence. Arise due to spontaneous pairing errors that occur during DNA replication, Arise due to mutagens like radiation or chemicals cause damage to the DNA. As a result :
- Change the amino acid sequence and thus, changes the protein- Different protein produced as the effect of mutation may not function as normal
Classify gene mutationi) Base substitutionii) Base insertioniii) Base deletioniv) Base inversion
mutation of base deletion and insertion make cause frame shift mutation Alteration of gene mutation cause some genetic disorders such as Sickle Cell Anemia
Classification of GeneClassification of Gene mutation:mutation:
Base substitution :
One or a few base pairs in the nucleotide sequences in genes is substitute Changes in base sequence results in changes of codon (UAU/UGU) 3 base/ nucleic acid = 1 codon (coding for 1 amino acid) Changes in codon:-
a) amino acid changes(missense mutation)
b) changes a codon to stop codon (nonsense mutation)
8/22/2019 Mutation Note
3/16
http://matriculation-biology.blogspot.com
Missense mutations are those that still code for an amino acid but change the indicated amino acid eg.Sickle Cell Anemia.
Nonsense mutations cNonsense mutations change an amino acid codon into a stop codon, nearly always leading to anonfunctional protein.
Sickle cell AnemiaSickle cell Anemia
mutant Hbs cause defective red blood cell. The cells are shaped like a crescent or sickle occurs more commonly in people regions where malaria is or was common. there is a survival value in
carrying only a single sickle-cell gene Those with only one of the two alleles of the sickle-cell disease aremore resistant to malaria, since the infestation of the malaria plasmodium is halted by the sickling of thecells which it infests.
sickle shape body produces abnormally shaped red blood cells.
Hbs stiff & tend to accumulate in small capillary, Hb is not efficient of transporting oxygen
polypeptide chain encode by different gen, cause differ one base only
Normal Mutantnucleotide T base is replaced by A base
DNA chain C T T C A T
transcript
mRNA G A A G U A
translation
code of amino acid glutamic valine
type of protein HB normal HB S
A change in a single nucleotide from T to A in the DNA template leads to an abnormal protein. Amino acid valine replaces glutamic acid at a single position in the protein
Base insertions
Addition of 1 or a few base pairs in the nucleotide sequences in genes mutation of base insertion make cause frame shift mutation
8/22/2019 Mutation Note
4/16
http://matriculation-biology.blogspot.com
Normal Mutantadditional nucleotide insertion with base G
DNA chain AGA GTC TTC AGA GGT CTT
transcript
mRNA UCU CAG AAG UCU CCA GAA
translation
code of amino acid Ser Gln Lys Ser Pro Glu
frame-shift happen
Base deletions
Loss of 1 or a few base pairs in the nucleotide sequences in genes mutation of base deletion make cause frame shift mutation
Normal Mutantlost of T base during replication of DNA
DNA chain AGA GTC TTC AGA GCT TCG
transcript
mRNA UCU CAG AAG UCU CGA AGC
translation
code of amino acid Ser Gln Lys Ser Arg Ser
frame-shift happen
Base inversion
2 base pairs or more are inverted in nucleotide sequence
Normal Mutant
inverted in nucleotide sequenceDNA chain AGA GTC TTC AGA TGC TTC
transcript
mRNA UCU CAG AAG UCU ACG AAG
translation
code of amino acid Ser Gln Lys Ser Thr Lys
Frame-shift MutationsFrame-shift Mutations
Involve insertion/deletion of a base pair or more into the nucleotides sequence of DNA Many of these deletions/insertion start in the middle of a codon Shifting the reading frame by one or two bases Frame shift mutations cause the gene to be read in the wrong three base groups (codon) From the mutation point, It abrupt the coding sequence of amino acid. Changes in codons results in changes in amino acids Different polypeptide is produced Effect ~ usually harmful to human E.g.: Major Thalasemia (mutant homozygote alleles)
8/22/2019 Mutation Note
5/16
http://matriculation-biology.blogspot.com
CHROMOSOMAL MUTATION
Definition: Abnormalities ~ in chromosomal structure (chromosome aberration) & changes inchromosome number (aneuploidy / euploidy)
Chromosomal mutations take place when the number of chromosomes changes or when structuralchanges occur in the chromosomes
Classification chromosomal mutationi) Chromosomal aberration (structural of chromosomal change)ii) Chromosomal number alteration
- Aneuploidy- Euploidy (polyploidy)
Chromosomes aberration
Changes in the chromosomes structure, are most frequently formed during mitosis or meiosis
Rearrangement a certain segment @ parts of chromosome 4 types of chromosomal aberration
i) Translocationii) Deletion (segmental deletion)iii) Inversioniv) Duplication
Analogy of frame-shift mutation
one sentencesCAN YOU BUY CAT FOR HER SON
after insertion only one alphabet , A at CAT in the sentence,CAN YOU BUY ACA TFO RHE RSO N
we can't read that sentence
after delete only one word, C at CAT in the sentenceCAN YOU BUY ATF ORH ERS ON
we can't read that sentence*peringatan analogi ini untuk kefahaman sahaja ianya tidak boleh digunakan dalam peperiksaan
8/22/2019 Mutation Note
6/16
http://matriculation-biology.blogspot.com
Translocation
Translocation : involves a region of a chromosome breaking off and rejoining either the other end of the samechromosome or another non-homologous chromosome
e.g. Robertsonian translocation Robertsonian translocation involves breaks at the extremes ends of the short arms of two
nonhomologous chromosomes (13, 14, 15, 21 and 22) Named after the American insect geneticist W.B.Robertson Also called whole-arm translocation or centric-fusion translocation
Deletion
Deletion: the lost of 1 segment containing 1 or more genes
When the chromosome breaks at two places and lead to the loss of the middle segment The segment lost may contain one or more genes The remaining end of chromosome will join again and become shorten Genetic disease: Cri du chat syndrome (usually mentally retarded and cries like a cat mewing) Loss of a small part of the short arm of chromosome 5 Cri du chat is a rare syndrome (1 in 50,000 live births) caused by a deletion on the short arm of
chromosome 5. The name of this syndrome is French for "cry of the cat," referring to the distinctive cry of children with
this disorder. The cry is caused by abnormal larynx development, which becomes normal within a few weeks of birth. Infants with cri du chat have low birth weight and may have respiratory problems. Some people with this disorder have a shortened lifespan, but most have a normal life expectancy. Where does the abnormal chromosome 5 come from? In 80 percent of the cases, the chromosome
carrying the deletion comes from the father's sperm.
8/22/2019 Mutation Note
7/16
http://matriculation-biology.blogspot.com
Inversion
Inversion: a region of a chromosome breaks off and rotates through 180 before rejoining thechromosome
Duplication
Duplication: a region of a chromosome becomes duplicated; an additional set of genes exists
When a single locus or a large piece of a chromosome is present more than once in the genome
8/22/2019 Mutation Note
8/16
http://matriculation-biology.blogspot.com
Alteration of chromosomes number
Type of the alteration of chromosomal numberi. aneuploidyii. euploidy / polyploidy
Human somatic cells containing a number of chromosomes which is not a multiple of 23 are called
aneuploids
Aneuploidy
Aneuploidy is a condition in which the number of chromosomes is abnormal due to extra or missingchromosomes, in other words, it is a chromosomal state where the number of chromosomes is not amultiple of the haploid set.
Normal diploid species have 2n chromosomes, where n is the number in the haploid set. Aneuploid individuals would have 2n-1 chromosomes (monosomy), 2n+1 chromosomes (trisomy), or
some other such arrangement. A change in the number of chromosomes can lead to a chromosomal disorder. Aneuploidy is common in
cancerous cells. Aneuploidy occurs during cell division when the chromosomes do not separate properly between the two
cells
Type of aneuploidy Genome situation
Monosomy 2n - 1
Trisomy 2n + 1
Tetrasomy 2n + 2
Disjunction: chromosomes separated to the opposite poles during meiosis
Non disjunction: failure of pair of chromosome to separate and to move to the opposite poles
both sets of chromosomes pass to the same pole of the cell
Cause of aneuploidy
Nondisjunction in Anaphase I & II
8/22/2019 Mutation Note
9/16
http://matriculation-biology.blogspot.com
Nondisjunctionin Anaphase I and II (meiosis)
Half the daughter cells produced have an extra chromosomes (n+1) whilst the other half have achromosome missing (n-1)
Fusion gametes between chromosome (n+1) and normal gamete (n), produced embryo with
chromosome (2n+1) : Trisomy; eg. Downs syndrome Fusion gametes between chromosome (n-1) and normal gamete (n), produced embryo with
chromosome (2n-1) : Monosomy; eg. Turner Syndrome
Autosomal abnormalities
Monosomy 21Trisomy 21 (down syndrome)
Monosomy
8/22/2019 Mutation Note
10/16
http://matriculation-biology.blogspot.com
Monosomy is the presence of only one chromosome from a pair in a cell's nucleus. Monosomy in human very rare, the majority embryos don't be survive, For live infant reported in human,
the only of monosomy 12
Monosomy 21
The syndrome is generally lethal and only several cases of living newborn infants have been reported,most of whom die between 3 weeks and 20 months of life but some survive into childhood.
Symptoms:- Short distance between eyes- Large ears- Contracted muscle- Large nose with a broad base- cleft lip and/or palate- Short neck- Short thorax- Small hands and feet, overlapping and/or flexed fingers and toes,- hyperactive reflexes (nervous system)
Trisomy
Trisomy is a presence genetic abnormality in which there are three copies, instead of the normal two,chromosomes of a particular numbered type in an organism
A trisomy is a type ofaneuploidy (an abnormal number of chromosomes) Human trisomy can occur with any chromosome. Most trisomies, like most other abnormalities in
chromosome number, result in distinctive and serious birth defects. Most trisomies result in spontaneousabortion; the most common types that survive to birth in humans are:- Trisomy 21 (Down syndrome)- Trisomy 18 (Edwards syndrome)
- Trisomy 13 (Patau syndrome)- Trisomy 9- Trisomy 8 (Warkany syndrome 2)- Trisomy 16 is the most common trisomy in humans, occurring in more than 1% of pregnancies. Thiscondition, however, usually results in spontaneous miscarriage in the first trimester
8/22/2019 Mutation Note
11/16
http://matriculation-biology.blogspot.com
A trisomy is theThus the presence of an extra chromosome 21 is called trisomy 21
Symptoms Down syndrome / trisomy 21
Short stature. A child often grows slowly and, as an adult, is shorter than average. Weak muscles (hypotonia) throughout the body. A child may seem to have less strength than other
children of the same age. A short, wide neck with excess fat and skin. Usually, this trait is less obvious as the child gets older. Short, stocky arms and legs. Some children also have a wide space between the big toe and second
toe. Respiratory problems
Where does the extra chromosome come from?
In 90% of Trisomy 21 cases, the additional chromosome comes from the mother's egg. This karyotype is an example ofDown Syndrome (trisomy 21), the most common numerical
abnormality found in newborns. It is characterized by an extra chromosome 21 and the karyotype is
written as: 47,XY,+21. The key to the karyotype description is as follows: 47: the total number of chromosomes (46 is normal). XY: the sex chromosomes (male). +21: designates the extra chromosome as a 21.
Sex chromosomal abnormalities
Aneuploidy, abnormalities in the sex chromosome number Non disjunction during spermatogenesis dan oogenesis e.g. Klinefelter syndrome (47,XXY) and Turner syndrome (45,XO)
8/22/2019 Mutation Note
12/16
http://matriculation-biology.blogspot.com
Non disjunction during spermatogenesis
If non disjunction during anaphase I & II sperm will have the abnormal sex chromosome : XY, XX @ YY Abnormal sperm x ovum (X) Klinefelter syndrome (XXY) Super male syndrome (XYY) 3X female (metafemale, XXX)
Non disjunction during Oogenesis
If non disjunction happened Some ovum might not carry any chromosome X & some others might carry 2 chromosome X Abnormal ovum (O) x sperm Turner syndrome (XO) YO : dead Abnormal ovum (XX) x sperm Klinefelter syndrome (XXY) 3X female
Klinefelter syndrome (47,XXY)
Klinefelter's Syndrome is a genetic disorder that happens in 1 in every 500 to 1000 male births. Instead of the normal XY chromosomes, these individuals have and extra X chromosome making them
XXY. Males with Klinefelter's syndrome have two X chromosomes (47-XXY), The X-chromosomes carry
genes in terms of development of testicles, sex hormone production and physical sex development ingeneral as well as to a certain extent also height growth.
It is named after Dr. Harry Klinefelter, a medical researcher at Massachusetts General Hospital, Boston,
Massachusetts, who first described this condition in 1942. Symptoms
delayed speech sensory integration difficulties, including sensitivity to noise hypotonia or low muscle tone auditory processing problems language-based learning disabilities, including reading difficulties anxiety depression gynecomastia or swelling of breast tissue during puberty
8/22/2019 Mutation Note
13/16
http://matriculation-biology.blogspot.com
Feminised male (soft voice Sterile male (small testis), failed to produce sperm long hand and leg
Turner syndrome (45,XO)
Turner syndrome results from a chromosomal abnormality in which a female infant is born with only oneX chromosome (instead of the usual two) or is missing part of one X chromosome.
Symptoms short stature "webbing" of the skin of the neck (extra folds of skin extending from the tops of the shoulders to the
sides of the neck) a low hairline at the back of the head low-set ears abnormal eye features, including drooping of the eyelids abnormal bone development, especially the bones of the hands and elbows a lack of breast development at the expected age (usually by age 13) an absence of menstruation (amenorrhea) a larger than usual number of moles on the skin
Abnormal Phenotype
Klinefelter Syndrome (XXY) : 2n+1 (Trisomy)
Sterile male (small testis), failed to produce sperm Feminised male (soft voice) & big breast, long hand and leg Non disjunction during oogenesis
Turner Syndrome (XO) : 2n-1 (Monosomy)
Sterile female (failed to ovulate) Small breast & undeveloped ovary
dwarf, deaf, abnormal heart & low IQ
Euploidy / Polyploidy
cell of organism that has an exact multiple of the haploid number (n) of chromosomes in a nucleus. Gametes fusion will produce cell which have more than 2 set of chromosome, for example: diploid (2n),
triploid (3n), and tetraploid (4n) nuclei or cell are euploid Occurred when a set of chromosome did not separate during gametogenesis Common in plants than in animals, cause gamete not occur in animal, while in plant can produce
vegetative propagate. Triploid (3n) occurs when
i) a gamete (2n) occur non disjunction fused with a normal gamete (n)
Gamete A x AA (non disjunction gamete)
individual of triploid AAAii) chromosomes disable to segregate during meiosis to produce diploid gameteiii) gamete from tetraploid organism (4n) fused with diploid organism gamete (2n).
e.g. plant triploid is a banana, lemon, rose, watermelon (seedless) and crysanthemum Tetraploid plants can be produced by :
8/22/2019 Mutation Note
14/16
http://matriculation-biology.blogspot.com
1) Somatic duplication of chromosome number
duplication of chromosome at callus (tip)
origin plant : AA (2n)
(Duplicate)
tetraploid plant AAAA (4n)
2) Fusion of two diploid gametes
P : AA (2n) AA (2n)
G : AA AA
FI: AAAA
2 types of polyploidy- Autopolyploidy- Allopolyploidy
Autopolyploidy:
Is an individual that has more than two chromosome sets, all derived from a single species The chromosomes set are homologous with the parent cell Importance in economic value which autopolyploid plants produce flowers and fruits bigger than normal
diploid plants Involve parent cell from one species mean homologous chromosome
P : AA (2n) AA (2n)
G : AA x AA
FI: AAAA
Allopolyploidy
A polyploid resulting from 2 different species (hybridization) interbreeding and combining theirchromosomes
The chromosome sets are different to parental cell mean non homologous chromosome sets involve F1 hybrids produced from different species are usually sterile (haploid set of chromosome from one
species cannot pair during meiosis with the haploid set from the other species) Chromosome number in a sterile hybrid becomes doubled and produces fertile hybrids (synapsis and
segregation can occur and viable gametes can be produced)
8/22/2019 Mutation Note
15/16
http://matriculation-biology.blogspot.com
Importance in producing new species e.g. plant (wheat)
Triticum diccoccum (2n = 4x = 28) x Aegilops squarrosa (2n = 2x = 14)Tetraploid plant
Triticum vulgare (2n = 6x = 42)
Hexaploid plant
P : AA BB
Gamete A x B
Hybrid ( sterile ) AB
duplication
AABB
Gamete, 2n = 2x ( fertile ) AB
8/22/2019 Mutation Note
16/16
http://matriculation-biology.blogspot.com
Spartina anglica is a spesies of cordgrass, It is an allopolyploid spesies derived from the hybrid Spartinax townsendii
P Spartina maritima (small cordgrass) x Spartina alterniflora (smooth cordgrass)
Hybrid Spartina x townsendii
dublication
Spartina anglica
Retold by
Amran Md SaidMatriculation College of Pahang.
The end.