DNA and Genes

Genetic diseases
1. Chromosomal disorder : structure or number

2. Single gene disoder

3. Poly gene disorder

• De novo/spontaneus mutations

• Inherited diseases, follow mendelian pattern

• Familial diseases: in one family more than one type

of cancer

• Multifactorial diseases: disease is caused by interaction

of different mutations and environmental factors

• Congenital something happen during organogenesis.

Some of the direct and indirect targets of networks of
differentially methylated and expressed genes

Courtesy Dr. V.W.Hu et al

 Genetic Diagnosis
• Medical history

• Family history, draw a pedigree

• Pregnancy history: Gravida status (G3P1A1)

• Race

• Dysmorphic Features
• Dominant character: only one allele needed to cause the
phenotype (heterozygous)

• Recessive character: both allels needed to cause the

phenotype (homozygous)
Autosomal dominant inheritance:

Aa aa

Aa

aa
Aa
Autosomal recessive inheritance:

aa Aa

aa Aa
Aa

aa
aa

Aa AA
 Things to find out:

• What is DNA?
• The Genetic Code
• The Human Genome
 The Cell
• Basic component of
life

• Two main categories,

prokarytic and
eukaryotic cells

• Differences in the
nucleus
• Genetic material is located in nucleus
• The genetic information is stored in
Deoxyribonucleic acid, DNA
• DNA contains the information needed to build
an individual
 What is DNA needed for?

• Genetic information is
transferred from DNA and
converted to protein

• RNA molecules work as

messengers

• Proteins are the biological

workers
• Information of the DNA is copied to a RNA
molecule in transcription

• RNA directs the

protein synthesis in a
translation

• Protein’s 3D structure
determines it’s function

• Information transfer
only in one direction
 DNA (Deoxyribo Nucleic Acid)

• a polymer of nucleotide monomers

• 2’-deoxyribose sugar Base part

• Four bases:
• Adenine, A
• Guanine, G
• Thymine, T
• Cytosine, C

Sugar part
 Four bases...
Purine bases Pyrimidine bases
• Adenine and • Thymine and
guanine cytosine
• Two carbon rings • A single carbon
ring
DNA Molecules
• Two polynucleotide
chains are joined

• Double helix,
twisted in right
handed way

• Full circle in every

10 bases
 The Genetic Code
• Describes how nucleotide sequence is
converted to protein sequence

• Unit of three nucleotides = a codon

• A codon codes for a specific amino

acid (structural component of protein)
• The four bases can
form 64 different
codons

• 20 amino acids are

found from the
nature

• Regulatory codons
Chromosome

Condenced scaffold

fibers connected to
chromosome scaffold

chromatin fibers

chromatin

DNA
 Genes

• A gene: DNA sequence that is needed to encode

amino acid sequence of a protein

• Composed of exons, introns and different control

elements

• Exon – protein coding sequence

• Intron – intervening sequence
• Genes vary a lot in size:
Humans: average 3000bp
largest 2.4 million bp

• Genes are separated by sequences with

unknown function

• Only one strand of the DNA carries

biological information 🡪 template strand

• Potential to store biological information is

enormous
The Human Genome and Inheritance
The Human genome...

The different types of sequences that make up

the total DNA of a human cell

• 3 billion base pairs

• about 22 000 genes

• Only 2 % of the DNA encode proteins

• Genes include exons and introns

• Beside coding areas also additional secuences are

found

• 50 % repeated sequences (”junk DNA”)

• 23 chromosome pairs 🡪 46 chromosomes

• 44 autosomes, 2 sex chromosomes

• X and Y –chromosomes

• XX 🡪 female

• XY 🡪 Male
 Mutations
• Alterations in DNA sequence

• Some are part of normal DNA variation

• Caused by chemical and physiological agents

and errors in DNA replication

• Cells can repaire some mistakes

• If not repaired changes in DNA sequence

are made permanent by DNA replication
Point mutations:
Single base mutations:

1. Missense mutation: leads to

an amino acid change

2. Silent mutation: does not

change the amino acid

3. Nonsense mutation: causes

premature stop-codon
• Frameshift mutations:
insertion/deletion
dublication
translocation

🡪 Altered reading frame

🡪 Severe impacts on protein structure
Passing on the genetic information:

• Information passed on in the sexual reproduction

• Needed for new characteristics to develop
• Offspring recieve genes by inheriting chromosomes
 Two important terms...

Phenotype: The outlook of an organism

Genotype: The genetic information written in DNA

Phenotypes

Genotype Genotype

GCCAAGAATGGCTCCCACC
ATGTTTCCACCTTCAGGTTCC
T
ACTGGGCTGATTCCCCCCTC
GGCTCTCAGACATTCCCCT
C
GGTCCAACCCCCAGGCCAT
CACTTTCAAGCTCGGCCCCT
CAAGATGTCTCAGAGAGGC
T
GGCTAGACACCCAGAGACC
TCAACTCAGAGAGGCGGCTA
TCAAGTGACCATGTGGGAA
GACACCCAGAGACCTCAAGT
CGGGATGTTTCCAGTGACA
GACCATGTGGGAACGGGATG
GGCA
All somatic cells
• 23 chromosome
Fertilization:
pairs
(46 chromosomes) +
• Diploid cells, 2n
n n
Sperm cell
• 23
chromosomes
• Haploid cell, n
Egg cell
• 23 Fertilized egg
chromosomes • 2n
• Haploid cell, n • 46
chromosomes
Mitosis

• Division of somatic cells

• Products two daughter cells

from
one parent cell

• The number of chromosomes

does not change

• DNA duplicates before entering

the mitosis

• Takes 1-2 hours

Meiosis

• Only in gamete formation

• One diploidic parent cell

produces
four haploid gametosytes

• Mature gametocytes have 23

chromosomes (n)
Crossing over:

• Chromatids change parts

between homologous chromatids
during the meiosis

• Causes redistribution of heridary

material between the homologous
chromosomes

🡪 number of genes doesn’t

change
🡪 new allele combinations
are formed