Central dogma, gene, gene expression, genetic code, genome, genotype, phenotype, trait, allele, mutation

1. Dr. Ifat Ara Begum
Associate Professor
Department of Biochemistry
Dhaka Medical College, Dhaka
Central Dogma, Gene, Genetic Code,
Codon, Genome, Genotype,
Phenotype , Trait, Allele, Karyotype,
Mutation & Mutagens
(Part I)
17/11/2020

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3. What is Central Dogma?
Information pathway
It is the flow of genetic information from DNA to mRNA & from mRNA to
protein
 It follows “Principle Of Colinearity”
[Linear base sequence of DNA of genetic code is decoded to the linear base
sequence of mRNA which is further decoded to the linear amino acid sequence
of protein / peptide ]
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4.  Three processes are included here:
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Information cannot be transferred back from protein to nucleic
acid.

5. Gene
 Hereditary factor
Unit of heredity / inheritance / genetic information
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6. Functional unit of DNA composed of coding region with its regulatory
sequences that carry genetic information (genetic code) encoded within
the base sequence of coding region
Arranged along the chromosome in linear order
 Approximately there are 30000 different genes in each cell
 Majority of gene are on chromosome (nucleus), small portion (37 gene)
on naked loop of mitochondrial DNA
 There may be protein coding gene or non coding RNA genes
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Protein coding gene:
Represent the majority of the total
gene
Are expressed in two stages:
transcription and translation
 They show incredible diversity in
size and organization and have no
typical structure
 There are, however, several
conserved features
Non coding RNA gene:
 Represents 2-5 % of the total
gene
Encodes functional RNA
molecules
[Many of these RNAs are involved
in the control of gene expression,
particularly protein synthesis]
They have no overall conserved
structure.

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9. Coding region of gene:
It is a mosaic of exons (E) & introns (I)
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Exons:
 Discrete units of DNA within the
coding segment
 Contain genetic code
 Included in mature mRNA & so
are expressed
Introns:
 Noncoding unit of DNA
interposed between exons within
the coding segment
 Are transcribed but not included
in mature mRNA
 So, they are not expressed

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11. Regulatory sequences / Transcription control sequences:
 Coding region of gene is flanked by its regulatory sequences
 Important regulatory sequences are:
- Promoter sequence
- Terminator sequence
- Enhancer
- Silencer
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12.  Regulatory sequence of gene is flanked by
- leader sequence in 5' (five prime) end
&
- trailer sequence in 3' end
 Leader sequence is called 5' UTR (Untranslated region)
 Trailer sequence is called 3' UTR (Untranslated region)
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Promoter sequence:
 Consists of TATA box, GC
box & CAAT box
 Lies towards 5' end
(upstream) of gene
 Initiates transcription
Terminator sequence:
 Lies towards 3' end
(downstream) of
gene
 Terminates
transcription
Enhancer:
 Lies in upstream /
downstream/ within
coding region of gene
 Accelerates
transcription
Silencer:
 Lies in upstream / downstream/ within coding region of gene
 Suppressess transcription

15. Gene Locus
Position / place occupied by a specific gene on a specific chromosome
It is mentioned with reference to centromere
(Connection point between 2 sister chromatids as chromosome splits
longitudinally)
 Genes don’t change the loci except
- in recombination during cross over phase of meiosis
or
- during alteration of chromosomal morphology.
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17. Genetic Code
Total genetic message encoded within the base sequence of exons
of the coding region of gene
 Anatomically, it is the collection of codons that specify amino
acids .
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Base sequence of genetic
code determines the
sequence of codons in the
coding region of gene
and
The sequence of codon
determines the amino acid
sequence of protein specific
for that gene

19. Codon / Coding Unit
Every individual three letter code word
of genetic code
Anatomically, it is triplet (three)
consecutive bases
[A, T, G & C at different
combinations]
Each codon represents one amino acid
 Total 64 codons: 61 sense codons & 03
nonsense / stop codons
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Sense Codon:
61 in number
 Each represents one amino acid to carry on protein synthesis
Nonsense / Stop Codon:
 03 in number (UAA, UAG, UGA)
 Does not represent any amino acid
 Used to terminate protein synthesis

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Universality:
A codon representing
a definite amino acid
is universal &
applicable to all
organisms
Degeneracy/ Redundancy:
 For a given amino acid, there is more than one codon (except
methionine & tryptophan)
Alteration mostly in 3rd base (from 5' to 3' direction) produces the
degeneracy to make diff codons for one amino acid
 e.g. Valine (GUU, GUC, GUA & GUG)
Commaless:
Between consecutive codons, there
is no extra base to separate the
codons
The last nucleotide of preceding
codon is immediately followed by
the first nucleotide of succeeding
codon
Specificity:
For a given codon,
there is only one
amino acid
Nonoverlapping
Consecutive triplet
codons don’t share
any base and follow
the strict sequence
along the reading
frame of mRNA.

23. Gene Expression
 The process by which
information (genetic code)
contained in a gene is
interpreted
Four steps in gene expression:
 Transcription
 Post transcriptional
modification
 Translation
 Post translational
modification
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25. Genome
 A genome is all genetic material of an organism (expressed and unexpressed)
Or
A genome is an organism’s full set of gene with total genetic instructions /
information encoded within the base sequence of DNA .
 Each genome contains all of the information needed to build that organism
and allow it to grow and develop.
 It includes both the genes (the coding regions) and the noncoding DNA, as
well as mitochondrial DNA
 The study of the genome is called genomics.
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 The human genome is a
complete set of nucleic acid
sequences for humans, encoded
as DNA within the 23
chromosome pairs in cell nuclei
and in a small DNA molecule
found within individual
mitochondria.
 These are usually treated
separately as the
nuclear genome, and the
mitochondrial genome.

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Every living organism
is
The Outward Physical Manifestation
of
Internally Coded Inheritable Information

28. Genotype
Inherited genetic constitution of an individual for any particular character /
trait
Genotype defines the phenotype of an individual
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29.  Fixed at fertilization
 Does not vary later on
Example:
Genotype of tall individual is TT or Tt
T: Dominant gene for tall
t: Recessive gene for short
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30. Phenotype
Physical appearance of an individual for any particular character / trait
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31.  Phenotype is potentially variable, as it is the product of interaction between
- Genotype
and
- Environmental factors
like intrauterine feeding, postnatal feeding, hormonal exposure, sunlight,
exercise, growing space etc
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32. As environmental factors (like endocrine and nutritional disorders)
can suppress the action of genotype
i.e.
an individual with tall genotype for height (TT) may be short
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35. Now, ask yourself

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38. Dr. Ifat Ara Begum
Associate Professor
Department of Biochemistry
Dhaka Medical College, Dhaka
Central Dogma, Gene, Genetic Code,
Codon, Genome, Genotype,
Phenotype , Trait, Allele, Karyotype,
Mutation & Mutagens
(Part II)
21/11/2020

39. Trait
Gene determined inherited physical characteristics
It may be:
i) Single gene trait : A trait determined by a single gene pair
ii) Polygenic trait : A trait determined by many genes.
Most of the hereditary traits are polygenic, are produced by complex
interaction of many genes & are conditioned by the environment
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40. Trait Phenotype
Gene determined inherited
physical characteristics
Physical appearance of an individual
for any particular character / trait
Eye color Blue eyes

42. Allele
An allele is one of the two (or more)
versions / forms of the same gene
occupying the homologous loci of
homologous chromosome
& controlling the same characteristics
(e.g. eye color)
but
producing different effects (e.g. black /
brown)
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Homologous Chromosome: Chromosomes
identical to each other in respect to
length, physical look, centromere
position, banding pattern & gene
distribution
Homologous Loci:
Identical pair of gene loci at identical
position of homologous chromosome

45. Genes Alleles
Sections of DNA that codes for
specific trait
Different forms of the same gene
Gene specifies a trait, e.g. Eye
color
Allele controls the same trait
producing different effects. i.e. Allele
specifies what will be the eye color –
blue / black / brown etc

46.  If two allelic genes occupying homologous loci are same:
Homozygous
 If not same: Heterozygous
e.g. Tall allele is “T” and short allele is “t”
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 TT or tt : Homozygous, expressed as
tall and short respectively
 Tt or tT : Heterozygous, expressed as
tall , because, ”T” is dominant allele
for tall over “t”, the recessive allele for
short

48. Karyotype
 Chromosomal constitution of an individual / cell
Or
The complete set of metaphase chromosome of an individual / cell
The procedure to make out karyotype of an individual: Karyotyping
Here, photographed metaphase chromosome of somatic cells are
obtained & arranged in order of decreasing length
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50. Short hand notion of karyotype follows a general rule that starts with the total
number of chromosome
followed by
sex chromosome complement
&
finally any abnormality
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51. Individual Karyotype
Normal male 46 XY
Normal female 46 XX
Down Syndrome (male) 47 XY + 21 (Trisomy 21)
Down Syndrome (female) 47 XX + 21 (Trisomy 21)
Turner Syndrome 45 X
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52. Mutation
Permanent change in the base sequence of DNA
involving coding or noncoding region
regardless of its functional consequences
 It reflects the balance between DNA damage & DNA repair
 If DNA damage fails to be repaired, mutation occurs
 Mutation occurs in a single gene or in chromosome
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54. Mutation in Coding region: Expressed Phenotypically
Mutation in Noncoding region: No phenotypic effect unless it occurs in
regulatory sequence of gene
(when it effects regulatory sequence of gene, there will be reduced gene
transcription & expression)
Mutation in germ cell (ova / sperm) : Will be transmitted to offspring & it
is heritable
Mutation in somatic cells: Will not be transmitted to offspring , produces
local phenotypic effect or adult onset disease in that individual only. e.g.
malignancy
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55. Causes of mutation / DNA damage:
 Error in replication: Mispairing of bases, Insertion of extra nucleotides
 Error in recombination events of DNA
 Exposure to mutagen
 Irradiation
 Spontaneous alteration or loss of base: e.g. Deamination of cytosine to
uracil
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56. Three types of mutation:
A. Genomic mutation:
Alteration of chromosome number in genome due to loss / gain of total
chromosome
B. Chromosomal mutation:
Microscopically detectable gross structural change in chromosome. e.g.
deletion, insertion, translocation
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58. Remember,
Transmission of genomic and
chromosomal mutation is less
frequent due to their low survival
rate
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59. C. Gene mutation:
Submicroscopic alteration of 1/ small number of bases.
It is 4 types:
 Point mutation
 Frame shift mutation
 Mutation by deletion /insertion of 3 / multiple of 3 bases
 Triplet repeat mutation
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60. i) Point Mutation:
Mutation caused by a change in a single nucleotide in a gene
sequence.
 It results when a DNA nucleotide is added, removed or
replaced by a different nucleotide
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61. Type of Point
mutation
What happens? Example Effect
Silent mutation Mutated / mutant
codon codes for the
same amino acid as
the parent codon
Parent codon GCU: Alanine
Mutant codon GCC: Alanine
None
Missense
mutation
Mutated / mutant
codon codes for a
different amino acid
Parent codon GAG: Glutamate
Mutant codon GUG: Valine
Variable. e.g.
Sickle cell
anemia (β chain
6th position)
Nonsense
mutation
Mutated / mutant
codon is a premature
stop codon
Parent codon CAG: Glutamine
Mutant codon UAG: Stop codon
Usually serious.
E.g. β
thalassemia
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ii) Frame shift Mutation:
It happens due to deletion/ insertion of 1/ 2 / >2 bases in a gene ( not 3 /
multiple of 3 bases)
Altered reading frame from the site of mutation onward. e.g. Duchenne
muscular dystrophy

63. iii) Mutation by deletion / insertion of 3 / multiple of 3 bases
abc def ghi jkl mno pqr
abc d↑ef ghi jkl mno pqr
(↑-> insertion of 3 bases xyz)
abc dxy zef ghi jkl mno pqr
(Reading frame of gene is not changed beyond the site of mutation)

64. In-frame mutations occur when the number of deleted or inserted base
pairs is a multiple of three. This results in a change in only a few amino acids; it
may still be possible for the protein to function, even though its sequence may
be slightly different.

65. iv) Triplet repeat mutation
 At the stage of full mutation, gene becomes hugely bulky that impairs gene
function
 Common diseases due to this mutation: Fragile-X syndrome, myotonic
dystrophy, Huntington disease

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67. Functional consequences of mutation:
Gain of function mutation: Expression of new function / increased
expression of normal gene function by the mutant gene.
Loss of function mutation : Expression of less/no activity by mutant gene
& reduction/absence of gene product
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68. Implication of mutation:
Source of all genetic variation
Adaptation to changing environment leading to long survival of species
Evolution
Pathogenic, so harmful
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