Chapter 14
The Human Genome
14-1 Human Heredity
• Human Chromosomes
– Can be visualized with a karyotype
– A karyotype shows the number and type of
chromosomes
• Humans have 46 chromosomes
– Sex chromosomes: 2
– Autosomal chromosomes (autosomes): 44
Human Traits
• Pedigree chart- a map of a characteristic’s
presence in related individuals
Dominant?
Recessive?
Male
Female
Dominant?
Recessive?
Male
Female
?
Male
Dominant?
Recessive?
Female
What determines a trait?
• Many characteristics can not be traced on a
pedigree chart:
– Most physical traits in humans are polygenic
– The environment can influence phenotype
Phenotype
Genotype
Genotype
Type A
IA IA
IA i
Type B
IB IB
IB i
Type AB
IA IB
Type O
ii
Phenotype
Genotype
Genotype
Antigen on
Red Blood
Cell
Type A
IA IA
IA i
A
Type B
IB IB
IB i
B
Type AB
IA IB
A and B
Type O
ii
None
Phenotype
Safe to
transfuse to:
Safe to
transfuse
from:
Antigen on
Red Blood
Cell
Type A
A, AB
A, O
A
Type B
B, AB
B, O
B
Type AB
AB
A, B, AB, O
A and B
Type O
A, B, AB, O
O
None
• Universal Donor- O
• Universal Recipient- AB
• Rh factor (Rhesus monkey)- either positive or
negative
• Rh+ phenotype = Rh+/Rh+ or Rh+/Rh- genotype
• Rh- phenotype = Rh-/Rh- genotype
Autosomal recessive disorders
• PKU (phenylketonuria)- lack an enzyme to break
down phenylalanine (an amino acid found in milk
and other foods)
– Can cause mental retardation
– Chromosome # 12
Autosomal recessive disorders
• Tay-Sachs disease- predominant in Jewish
families
• Nervous system breakdown and death in first few
years
Autosomal recessive disorders
• Cystic Fibrosis- Excess mucus in lungs, digestive
tract, liver. More susceptible to infections
Dominant disorders
• Achondroplasia- dwarfism
– Caused by a dominant gene
Huntington’s Disease- nervous system disorder,
causes progressive loss of motor control and
mental function. Symptoms appear in 30s
Codominant disorders
• Sickle Cell Disease- red blood cells are sickle
shaped. They get stuck in capillaries and stop the
passage of blood. It causes physical weakness
and damage to brain and heart.
From Gene to Molecule
• What causes genetic disorders?
• A change (mutation) in the DNA
From Gene to Molecule
• Cystic Fibrosis (CF)- caused by a
deletion of three bases on chromosome 7
in the middle of a sequence for a protein.
A Phenylalanine amino acid is missing.
This protein allows chloride ions to pass
across membranes.
– Heterozygous- asymptomic, they
produce enough of the protein.
From Gene to Molecule
• Sickle Cell Disease- a one base pair change of
thymine to adenine. Amino acid glutamic acid is
changed to valine.
• Malaria- a parasitic disease common in West
Africa
• Sickle Cell
– Homozygous dominant- susceptible to malaria
– Heterozygous- resistant to malaria
– Homozygous recessive- sickle cell disease
14-2 Human Chromosomes
• 97% of human DNA does not code
for a protein. Average gene length is
3,000 base pairs
• Chromosome 22
– 545 genes, mutations can cause
leukemia, and tumors of nervous
system
Chromosome 23
225 genes, amyotrophic lateral
sclerosis (ALS), Lou Gehrig’s
disease
Sex-Linked Genes
• Sex-Linked Genesdisorders found on the X or
Y chromosome.
– X linked disordersmore than 100
– Y linked disorders- very
few
Sex-Linked Genes
• Colorblindness- defect on the X chromosome
• Red-green colorblindness- 1 in 10 males in the
US, 1 in 100 females
Sex-Linked Genes
• Males have only one X chromosome. Any
mutation is expressed. There are no heterozygous
genotypes.
Sex-Linked Genes
• Hemophilia- a protein necessary for blood clotting
is missing. The gene is carried on the X
chromosome.
• 1 in 10,000 males have hemophilia
• Can be treated with injections of clotting proteins
produced by recombinant DNA technology.
Sex-Linked Genes
• Duchenne Muscular Dystrophy- weakening and
loss of muscle.
X- Chromosome Inactivation
• Females have two X chromosomes
– One is randomly switched off
– This forms a Barr body
• In cats the X chromosome controls part of the coat
color. Orange and black colors are on the same
chromosome.
Chromosomal disorders
• Nondisjunction- chromosomes fail to separate in
meiosis.
Chromosomal disorders
• Down syndrome- mild
to severe mental
retardation
• Caused by trisomy of
chromosome 21
Down syndrome
Sex Chromosome Disorders
• No X or Y- fatal- fetus does not develop
• Turner’s syndrome- one X, females are sterile,
sexual organs do not develop
• Klinefelter’s syndrome- males with extra X, XXY,
14-3 Human Molecular Genetics
• Human DNA Analysis
– There are genetic tests for CF and Tay-Sachs
disease
– How do they work?
• Cystic Fibrosis (CF)- caused by a deletion of
three bases on chromosome 7 in the middle of a
sequence for a protein. A Phenylalanine amino
acid is missing.
• XXX-XXX-XXX-XXX-AAA-XXX-XXX-XXX Normal
• XXX-XXX-XXX-XXX-XXX-XXX-XXX CF
• How can we distinguish between the two types of
DNA with our molecular tool kit?
• AGA-CTC-TTT-GAG-AAA-CCG-CCG-ATA
• AGA-CTC-TTT-GAG-CCG-CCG-ATA
• Restriction enzyme:
– cuts at GAAACC into GAAA CC
• AGA-CTC-TTT-GAG-AA
A-CCG-CCG-ATA
• AGA-CTC-TTT-GAG-CCG-CCG-ATA
• How can we separate the DNA?
• AGA-CTC-TTT-GAG-AA
A-CCG-CCG-ATA
• AGA-CTC-TTT-GAG-CCG-CCG-ATA
• How can we separate the DNA?
• AGA-CTC-TTT-GAG-AA
A-CCG-CCG-ATA
• AGA-CTC-TTT-GAG-CCG-CCG-ATA
• Gel Electrophoresis
DNA Fingerprinting
• DNA Fingerprinting- used to identify individuals
based on differences in DNA
DNA Fingerprinting
• Most functional genes are identical in humans
• Differences in DNA often occur in the 97% of DNA
that does not make functional proteins. Much of
our DNA is repeated segments of the same
sequence.
• XXXXXX-gene-XXXX-gene-XXXXXX-gene-XXXX
• XXXX-gene-XXXX-gene-XXXXXXXXXX-gene-XX
DNA Fingerprinting
• XXXXXX-gene-XXXX-gene-XXXXXX-gene-XXXX
• XXXX-gene-XXXX-gene-XXXXXXXXXX-gene-XX
• Restriction enzymes cut at regions that are highly
variable. Gel electrophoresis separates the DNA
based on size.
• Everyone has a unique pattern of fragments that
are produced when their DNA is cut by restriction
enzymes.
The Human Genome Project
• E. coli has 4.6 million base pairs
• Humans have a total of 6 billion base pairs
– 3 billion in a haploid cell
1990 The Human Genome Project began
purpose was to sequence the entire human
genome
The Human Genome Project
• Working copy- 2000
• Complete copy- 2003
• Public vs Private debate
– Should DNA be patented?
– Craig Venter- Celera Genomics
Shotgun sequencing- cut DNA into random
fragments, sequence the fragments, use
computers to put together the pieces
The Human Genome Project- Findings
• Very few genes- 35,000
– E. coli : 14,000; round worm: 20,000
Looked for promoter sequences to find genes
Gene Therapy
• Gene Therapy- an absent or faulty gene is
replaced by a normal, working gene
• First attempted in 1990. First success- in 1999 a
young French girl has her bone marrow removed,
modified, and reinserted.
Gene Therapy
• 1. A virus is modified with the correct DNA
sequence for a protein.
Gene Therapy
• 2. The virus infects human cells, injects the DNA
into the cell.
Gene Therapy
• 3. The cell will then start transcribing and
translating the DNA sequence to make the correct
protein.
Ethical Issues in Human Genetics
• Should we attempt to cure diseases by
manipulating DNA?
• Should we attempt to modify human DNA to
create enhancement?