Topics of Discussion

 Human Genome Project

 Population Genomics
 Personalized Medicine

Presented By:
Komal Zafar
(MPhil Biochemistry)
Presented to:
Dr. Mohibullah Shah

Department of Biochemistry
BZU, Multan
 Human Genome Project
• Human genome project is an international effort to clone and
sequence the entire human genome.
• Its goal was the complete mapping of all genes of human beings.
• Idea was picked up in 1984 by US govt.
• HGP is a 13 year effort which is coordinated by the:

1- Department of energy (DOE)

2- National institute of health (NIH)
 History of HGP

1988–1992 1999–2003
First stage Third stage
• Period of development and implementation • HGP was completed in 2003

Second stage
• Genome was divided into 23 natural
subunits

1993–1998
 m e n o . 2 1
Chromoso
 Goals of HGP

 To discover the complete set of human

genes.
 To determine complete sequence of DNA
bases.
 To store this information in databases.
 To sequence genome of other organisms
such as mouse, drosophila etc.
 Process of determining the human genome
involves:
Genome Mapping:
Technical  To identify and record location of genes
 Distance between genes on
aspects in chromosomes

HGP: DNA Sequencing:

 To determine nucleic acid sequence in
DNA
 Mapping Strategies:
 Genetic markers e.g., RFLP
Strategies: Sequencing Strategies:
 Shotgun sequencing method
 Sanger sequencing method
 RFLP
• RFLP is used for the analysis of unique patterns in DNA
fragments in order to genetically differentiate between
organisms.
• These patterns are called Variable Number of Tandem Repeats
(VNTRs).
•  RFLP analysis can be used as a form of genetic testing to
observe whether an individual carries a mutant gene for a
disease that runs in his or her family.
Sanger
Sequencing
 Shotgun Sequencing

• Shotgun sequencing is the most efficient way to sequence a large piece of

DNA.
• The method involves breaking the genome into a collection of small DNA
fragments that are sequenced individually.
• A computer program looks for overlaps in the DNA sequences and uses them
to place the individual fragments in their correct order to reconstitute the
genome.
 Genome Mapping in
Pakistan:
 In 2011, Pakistan
became the world’s
sixth country and the
first Muslim state to
map the genome of
the first Pakistani
individual.
 Dr. Atta-ur-Rehman
was the first Muslim
and Pakistani whose
complete genome was
mapped.
 The whole process
costed US 40,000$ and
was equally
contributed by PCMD
 Molecular medicine

DNA forensics
Applications
of HGP:
Agricultural and Environmental
applications
Pharmacogenomics
 • The goal of the 1000 Genomes Project was to find
The 1000 most genetic variants with frequencies of at least 1%
Genomes in the populations studied.
• Finding places where human genome differs.
Project • It was the first project to sequence the genomes of a
large number of people, to provide a comprehensive
resource on human genetic variation. 
 4 million sites that 100 changes that
differ from human knockout gene
reference genome function

Magnitude
of Variation
12,000 changes to 5 rare variants that
proteins are known to cause
diseases
• Each point on this graph
represents a single genome.
• Distances between points
represent similarity or differences
between individual genome.
• Clustering indicates sharing of
common ancestry.
 Whole genome sequencing of an ethnic Pathan
(Pakhtun) from the north-west of Pakistan

• Genomic variations including single nucleotide variations (SNVs), small

insertions and deletions, and copy number variation regions (CNVRs) were
identified by aligning the Pathan genome sequence to the Human
Reference Genome (hg19). 

Total Homozygous Heterozygous SNVs mapped to % of SNVs Novel % of Novel

dbSNP (v137) mapped to
dbSNP
SNVs SNVs SNVs
SNVs SNVs

3,813,440 1,272,912 2,540,528 3,683,999 96.6% 129,441 3.39%

•Copy number variation regions in
Pathan genome
•Admixture results of Pathan (PTN)
individual to other ethnic groups in
South Asia 
 Uses:
 Imputation, screening in the identification of
pathogenic variants
 Supporting evolutionary and population genomics
research, assessing the impact of variations on gene
expression.
 Data help medical researchers link genetic variants
to diseases.
 1000 Genomes Project samples are also of particular
use to those investigating new technologies and
methods, where existing resources can be used for
comparison. 
 Population Genomics:
• Population genomics studies the evolution of genome variants in
populations.
• In humans, it refers to applying technology to understand how genes
contribute to our health and well-being.
• This approach was first proposed by Lewontin and Krakauer in 1973.
• Population genomics is applied to development of the HapMap project.
 HapMap Project

HapMap is a tool that allows researchers to Goal is to determine the common patterns of DNA
find genes and genetic variations that affect sequence variation in the human genome.
health and disease.
Types of Genetic Variation
There are 3 sources of variation:
 Mutation
 Recombination
 Immigration of genes
The source of all variations must be mutation.
Probability that a copy
of an allele changes to
some other allelic form
in one generation.

Pieces of DNA are

broken and recombined
to produce new
combinations of alleles.

Movement of
individuals from one
population to another.
 Population Genomic Evidence for Recent and Rapid
Evolutionary Adaptation in Humans
 People moved from low elevations to occupy
some of the highest plateaus and mountain
Case Study: ranges in the world.
 These populations exhibit heritable physiological
attributes that allow individuals to function at
high altitudes (3250–4500 m) with low oxygen
concentrations that are challenging to humans
from lower elevations.
 Applications:
Understanding the evolutionary processes
affecting genomes.

Understanding the roles of evolutionary

processes, such as mutation, genetic drift, gene
flow, and natural selection.
In shaping up genetic variation at individual loci
and across the genome and populations.
Personalized Medicine
• Personalized medicine is the tailoring of medical
treatment to the individual characteristic of each patient.
• Other names for personalized medicine are:

Precision medicine
Stratified medicine
Targeted medicine
Pharmacogenomics
•Genome sequencing will allow for a more Accurate and
targeted therapy for different patients
 Need for personalized
medicine:

 Similar symptoms but different illness.

 Advances in genomics to treat patients
effectively.
 Better matching patients to drugs
instead of trial and error.
 To avoid allergic and adverse effects.
 Implementation
• The full implementation of personalized medicine encompasses:
1. Risk assessment
2. Prevention
3. Detection
4. Diagnosis
5. Treatment
6. Management
 Benefits

Better matching Reduce cost of Improved efficacy

patients to drugs clinical trials of drugs

Elimination of life
Early detection of
threatening
disease
adverse reactions