CENTRAL DOGMA OF

MOLECULAR BIOLOGY
Mazidah Zulfa
Suci Rahmayanti
 Central Dogma

DNA code is transcribed as mRNA code and

then translated as amino acid code of the
resulting protein
Approximately 95% of DNA does
not code for proteins and may be
involved in regulation of gene
expression.
Genes control cellular activity
through 2 processes:
1. Transcription (expression)
2. Translation
• There are feedback and regulatory mechanisms of gene
expression that are both genetically and environmentally
determined.
• These mechanisms, such as methylation and histone
formation, can silence gene expression. In addition,
small segments of RNA can block mRNA.
• The study of the influence of these regulatory
mechanisms in gene and disease expression is known as
epigenetics.
 Transcription factors are proteins
that bind to specific DNA
sequences and thus control the flow
(or transcription) of genetic
information from DNA to mRNA.
Transcription factors perform this
function by promoting or repressing
the recruitment of RNA polymerase
to specific genes.
 Approximately 10% of genes in the
human genome code for
transcription factors. They contain
one or more DNA-binding domains,
which attach to specific sequences
of DNA adjacent to the genes that
they regulate.
Many ophthalmic disease result from
transcription factor mutation:
•PAX6 mutations  aniridia, occasional
cases of peters anomaly, and several other
rarer phenotypes, specifically autosomal
dominant keratitis and dominant foveal
hypoplasia.
•PAX2 mutations  colobomas of the Phenotypic expression of aniridia with PAX6 gene mutation.
The aniridic probands showed typical features of sclerocornea with nystagmus in
optic nerve and renal hypoplasia proband 28–1 (A); Foveal hypoplasia in proband 27–1 (B);

•PAX3 mutations  waardenburg

syndrome with dystopia canthorum

Source : PAX6 gene variations associated with aniridia in south India

May 2004. BMC Medical Genetics 5(1):9. DOI: 10.1186/1471-2350-5-9.
Intron Excision

 Messenger RNA undergoes excision of the introns by a highly

organized process called splicing  composed of only exons, or
coding segments  undergo translation in the ribosomes.
 Splicing takes place in specialized structures called spliceosomes
 Errors of splicing can lead to genetic disease.
 Approximately 15% of point mutations that cause human disease do
so by generating splicing errors (Such as exon skipping, intron
retention, or use of a cryptic splice site)
 For example, mutations in proteins that are vital in splicing can cause
retinitis pigmentosa (RP).
Intron Excision/Splicing
 Alternative Splicing and Isoforms
 Alternative splicing is the creation of multiple pre- mRNA sequences from the
same gene by the action of different promoters.
 These promoters cause certain exons to be skipped during transcription of the
gene.
 The protein products of alternative splicing are often called isoforms.
 The promoters are usually tissue specific, so different tissues express different
isoforms.
 The gene for dystrophin is an example of alternative splicing: full- length
dystrophin is the major isoform expressed in muscle; shorter isoforms
predominate in the retina, peripheral nerve, and central nervous system.
 Alternative Splicing and Isoforms
 Another example of alternative splicing’s relevance underlies the basis of the
cornea’s avascularity.

 Vascular endothelial growth factor (VEGF) receptor 1 is a key blood vessel receptor
that binds and transduces a signal from the primary mediator of angiogenesis, VEGF.

 In the cornea, high levels of an alternatively spliced isoform, soluble VEGF receptor
1 (sVEGFR-1), are expressed. As this isoform is soluble, it is present in the
extracellular matrix and serves as an endogenous VEGF trap or decoy receptor.
Without it, there are increased levels of free VEGF, and the cornea becomes
vulnerable to vascular invasion.
Methylation
A biological process by which methyl
groups are added to the DNA molecule.
It can change the activity of a DNA
segment without changing the
sequence
Evidence suggests a close correlation
between methylation and gene
inactivation.
Methylation may account for variation
in phenotypic expression of some
diseases.
 X- Inactivation
 The random inactivation of 1 of the 2 X chromosomes in the
female, resulting in the lack of expression of the majority of genes
on that chromosome
 The time of X- inactivation is not precisely known but is thought to
vary over a period of several cell divisions during the blastocyst–
gastrula transition.
 Also known as lyonization (as the discoverer, Mary Lyon).
Lyonization affects the severity of the phenotype of several X-
linked retinal conditions, such as RP and incontinentia pigmenti.
 Imprinting

 A heritable yet reversible process by which a gene is modified, depending on

which parent provides it.
 The mechanism is unclear but appears to operate at the chromatin organization
level and involves heterochromatization and methylation of CpG (cytosine-
phosphate- guanine) sites.
 Examples of genes that can be imprinted include the Wilms tumor– suppressor
gene and the human SNRPN (small nuclear ribonucleoprotein polypeptide N)
gene.
 Prader- Willi and Angelman syndromes are examples of diseases resulting from
abnormalities of imprinting.
Imprinting
 Approximately 70%–80% of patients with Prader- Willi syndrome harbor a deletion of the
paternally derived 15q11– q13, resulting in the loss of this region’s normal contribution from the
paternal line.
 About 70%–80% of patients with Angelman syndrome also have a deletion of 15q11– q13, but
from the maternally derived chromosome, resulting in loss of the maternal contribution.
TERIMA KASIH
MOHON ARAHAN DAN BIMBINGAN