introduction to human genome

1. Human
genome

2. History
• 1980s – Nucleotide sequences
of important genes from
humans and other organisms
had been determined
• 1990s – Nucleotide sequence
of entire genome of
H.influenzae was determined
• 1st targets of genomic research
were pathogenic bacteria

3. What is a genome?
Genome : All of the DNA for
an organism
Human Genome
•Nucleus : 3 billion base pairs packaged
into chromosomes
•Mitochondrion : 16,600 base pairs
packaged in one circular chromosome

5. Types of DNA

6. Difference between types of DNA

7. Packaging of
DNA

8. Need for packaging
Packaging here
refers to the
condensing of DNA
to fit easily into the
nucleus.
01
Process of
packaging differs in
prokaryotes and
eukaryotes.
02
In prokaryotes the
chromosomes are
present freely in the
cytoplasm hence
packaging is not
required.
03

9. Order of Packaging

10. Nucleosome
Solenoid
Fibre
Scaffold
loop
1st Order 2nd Order 3rd Order
Thus the 3 main order of DNA Packaging are:

11. 1. Nucleosome
• “Beads on a string”
• Histones are responsible for the 1st level
of DNA packaging in chromatin
• The fundamental DNA packing unit

12. Histone Proteins
The complexes between eukaryotic DNA and proteins are called
chromatin.
The major proteins of chromatin are the histones-small proteins
containing a high proportion of basic amino acids (arginine and
lysine) that facilitate binding to the negatively charged DNA molecule.
There are five major types of histones called H1, H2A H2B, H3, and
H4.

13. Linker DNA comprises the rest of the
repeating unit. Its length varies from as
little as 8 bp to as much as 114 bp per
nucleosome (H1) .
Core DNA has an invariant length of 146
bp, and is relatively resistant to digestion
by nucleases (H2A, H2B, H3, H4).

14. 2. Solenoid
• Secondary chromatin structure
• A solenoid is a condensed chromatin fibre
with 30nm diameter.
• Helps to package eukaryotic DNA into the
nucleus.

15. 3. Chromosomal Scaffold
• Regions of the DNA interact with chromosomal scaffold proteins to give a
protein core with DNA loops sticking out of it.
• 30 nm filaments is appear to be organized in loops estimated at 40 to 100
kbp long.
• Chromosomal scaffold: Proteinaceous residue after extraction of
histones from chromosomes, comprised mainly of Structural
maintenance of chromosomes (SMC) proteins.

16. Chromosome scaffold
constituent proteins are also
called scaffold protein.
Chromosome scaffold is
made of proteins including
Condensin and kinesin
family member 4 (KIF4)

17. Summary of
DNA
packaging

18. Chromatin can
be classified as
Chromatin
Heterochromatin
Constitutive
Heterochromatin
Facultative
Heterochromatin
Euchromatin

23. Human DNA 3.2 x 109 bases distributed over
23 chromosomes.
Chromosomes in Human

24. Structure of
Chromosome:

25. Centromere and
Kinetochore
Centromere:
Constricted region of
chromosomes that
holds the sister
chromatids together.
Kinetochore:
Complex protein
containing structure to
which microtubules
attach

26. Types of
Chromosome
bases on the
location of
centromere

27. Telomere
• A telomere is a region
of repetitive
DNA sequences at the end
of a chromosome.
• Telomeres protect the ends
of chromosomes from
becoming frayed or tangled.

28. • Each time a cell divides, the
telomeres become slightly
shorter.
• Eventually, they become so
short that the cell can no
longer divide successfully, and
the cell dies

29. Karyotype
• Karyotyping is a process of pairing,
arranging, and chromosomal
organization to find out the pattern in
chromosomal variations using a
karyogram.
• During the metaphase of the cell division
cycle, a stained photograph of a nucleus
having chromosomes is taken, which is
known as a karyogram in which all the
chromosomes are organized from larger
to smaller in size and numbered with
genetic chromosomes in the last.

30. Homologous
chromosomes
• Homologous
chromosomes are made up
of chromosome pairs
of approximately the
same length, centromere
position, and staining
pattern, for genes with
the same corresponding
loci.

32. Gene Vs Genome
A gene is a molecular unit
of heredity on a living
organism.
The genome is the entirety
of an organism's hereditary
information. They are
encoded in DNA
molecules.

33. • The study of genome
characteristics related to
organisms is called as
Genomics.

34. Gene consist of:
• Bind transcription factors that can activate or
inhibit transcription
Transcriptional
control sequences:
• Recruit RNA polymerase and marks the start
of transcription
Promoter
• Corresponds to the RNA sequence
Transcript
• Terminate trasncription
Termination
sequence

35. Central Dogma of Biology

36. Human Genome Project

37. What is Human Genome project?
The Human Genome Project was a large, well-organized, and highly collaborative
international effort that generated the first sequence of the human genome and that of
several additional well-studied organisms. Carried out from 1990–2003, it was one of the
most ambitious and important scientific endeavors in human history.

39. Who took part
in the project?
• Twenty institutes from six different countries
(China, France, Germany, Japan, UK and
USA)
• Wellcome Trust Sanger Institute
• Washington University School of Medicine
• Whitehead Institute/MIT centre for
Genome research
• The DOE’s Joint Genome Institute
• Baylor College of Medicine

40. Pioneers in Human genome project
• Robert Sinsheimer- proposed the idea
• Charles DeLisi and David Smith- proposed the budget
• James Watson- headed the NIH Genome Program
• Francis Collins- succeeded James Watson in 1993
• Jim Kent- developed a software, GigAssembler that allowed
HGP to assemble and publish the human genome sequence

41. Technical aspects
Genetic mapping
(Characterizing
the chromosomes)
DNA Sequencing
(Determining the
order of bases)

42. 1. Mapping strategies
• Genetic markers are invaluable
for genome mapping.
• Markers are any inherited
physical or molecular
characteristics that are different
among individuals of a
population (polymorphic)
• A genetic map shows the relative
locations of these specific
markers on the chromosomes.

43. Determining the exact order of the bases
in a strand of DNA.
To assemble the sequence of all the
bases in a large piece of DNA such as a
gene, researchers need to read the
sequence of overlapping segments.
Two methods were used:
1. Short Gun sequencing
2. Sanger’s Sequencing

44. A. Shortgun
sequencing
1. DNA extraction
2. Fragmentation of Genomic
DNA
3. Insertion in vectors to form
DNA library
4. Sequencing of library

45. B. Sanger’s
Sequencing
Dideoxy chain termination
method.
It generates nested set of labelled
fragments from a template strand
of DNA to be sequenced by
replicating that template strand and
interrupting the replication process
at one of the four bases.

46. Some outcomes of Human Genome project
• The human genome contains 97% repetitive junk DNA content.
• Only 2 to 3% portion of the genome encodes proteins
• The human genome contains 3.2 bbp, which means 6.4 bases which are
approximately 3164.7mb.
• Around 25,000 to 30,000 genes are present in the human genome in which the
average length of a gene is 3000 base pairs.
• The largest gene is the dystrophin having 2.4Mb in size.
• All the genetic content of a cell is located on 23 pairs of chromosomes.
• The genome of us has 1.4 million known SNPs.