BIOPHARMACEUTICS

ASSIGNMENT NO.02
SUBMITTED TO

SIR MOSA RAZA

SUBMITTED BY

1. HASRIS JAVED 70101661

2. UZAIR ASLAM 70099245

3. SUFYAN IFTIKHAR. 70099859

4. BILAL AHMED. 70100017

5. M. UMER KHAN 70099293

6. HASHAM. 70094784

7. MAHTAB KHALID. 70099347

8. RASHID BASHIR 70101282

9. SHAHZAD

10. HAMAD
11. KHURAM 70099447

12. HAROON AKRAM. 70098373

13. MUHAMMAD USAMA 70095030

14. ABDULLAH TARIQ. 70094397

 Assignment # 02
Genetic
Polymorphism
Contents:
 Terminologies.
 Introduction.
 Causes.
 Types.
 Single nucleotide polymorphism.
 Uses and importance.
 Insertions and deletions.
 Polymorphism in plasmodium falciparum.

Terminologies:
Malaria -Malaria is a life-threatening mosquito-borne blood disease caused
by a Plasmodium parasite. It is transmitted to humans through the bite of the
Anophelesmosquito.
Genetics- Genetics is the study of genes, genetic variation, and heredity in
livingorganisms
Polymorphism- Polymorphisms are a type of genetic diversity within a
population‘s gene.
A frequency of 1% or more is generally considered to be a polymorphism.
Exons- An exon is any part of a gene that will encode a part of the final
matureRNA produced by that gene after introns have been removed by RNA
splicing.
Locus- the physical location a gene occupies within a chromosome or portion
ofgenomic DNA.
Allele: alternative forms of a gene that arise by mutation and are found at the
sameplace on a chromosome.
Chromosome: a nuclear structure carrying genetic information arranged in a
linearsequence.
Genome: The genome is the genetic material of an organism, that is,
the totalamount of DNA in the cell.

Introduction.
Poly =multiple , morph= forms.

A genetic polymorphism is the existence of two or more variants - which may

be allelic, phenotypic, chromosomal or general DNA sequence variants - at
significantfrequencies in a population. A frequency of 1% or more is generally
considered to be a polymorphism.

Causes:
Genetic polymorphisms are caused by duplications, deletions, and a mutation
oftriplication of high quantity of DNA base pairs sequences.
Polymorphisms may occur due to changes inside introns or changes in
regions ofone or multiple DNA bases that are between genes.

Types of genetic polymorphism:

1: Single nucleotide polymorphism

(SNP)2: Insertion and deletion (INDEL)
3: Short tandem repeats (STR)
Single nucleotide polymorphism:

DNA sequence variation occurring when a single nucleotide — A, T, C, or

G inthe genome differs between members of a biological species.
A single base pair mutation at a specific locus, usually consisting of two
alleles.For a variation to be considered a SNP, it must occur in at least 1% of
the population:
Two types:
 Synonymus and
 non –synonymus
Synonymus:
SNP in which both alleles produce the same polypeptide sequence is known
assynonymous.
Sometimes called silent mutation.

non –synonymus:
If different polypeptide sequence is produced they are non -synonymous.
A non- synonymous change may either be missense or nonsense, where a
missensechange results in different amino acid, while a nonsense change
results in a premature stop codon.
Insertions and deletions.

“INDELs,” is a type of genetic variation in which a specific nucleotide

sequence ispresent (insertion) or absent (deletion).
Small insertions/ deletions are existed on genes coding exons and this may
consider a fundamental factor that leads to diseases inheritance in humans.

Microsatellites:

Also known as the Simple Sequence Repeats (SSRs),and single tandem

repeats(STR).
Microsatellites are stretches of DNA, consisting of tandemly repeating mono
-, di-,tri-, tetra-, and penta- nucleotide units, which are arranged through
the genome of most eukaryotic species.
They are typically neutral, co- dominant and are used as molecular markers.
Uses and importance:
 Variations in the DNA sequences can affect how humans develop
diseasesand respond to pathogens, chemicals, drugs, vaccines, and
other agents.
 Their greatest importance in biomedical research is for comparing
regions ofthe genome between with and without a disease in genome.
 They are usually biallelic and thus easily assayed.
 SNP maps help to identify the multiple genes associated with
complexailments such as cancer, diabetes, vascular disease, and
some forms ofmental illness.

Polymorphism in plasmodium falciparum:

 Plasmodium- In 1880 scientists discovered the real cause of malaria
was aone-cell blood parasite or protozoa called Plasmodium.
 There are four species of Plasmodium that infect humans.
 P.falciparum, p.ovale, p.vivax, p.malariae.

Plasmodium falciparum:
 It is the commonest species in Africa and it accounts for 95 - 98%
of allmalaria infections.
 It is responsible for severe illness cerebral malaria and other
complicationsand may cause death.
 The length of asexual cycle is about 48 hours.
 The emergence and spread of Plasmodium falciparum parasites
resistant to anti-malarial drugs, such as chloroquine(CQ), amodiaquine,
pyrimethamine,
 and sulfadoxine, have been shown various genetic alterations
associatedwith these drugs.
 Genes which is identified as potential candidates of drug resistance
are P.falciparum multidrug resistance gene (Pfmdr1),CQ resistance
transportergene (Pfcrt), Dihydrofolate reductase
(Pfdhfr),Dihydropteroate synthase (Pfdhps).