Download Principles of Heredity

From the Gene to the
Genome
Genetic Inheritance Patterns
Observing Genetic Differences in
the DNA
Each human has 46 chromosomes.
Each parent provides one member of a
matched (homologous) chromosome pair.
Chromosomal Locations of Genes
• Locus = area on chromosome where
gene is located
• Paired chromosomes have genes in
the same order, but may have
different forms of a gene at the same
locus
• Alleles = alternative forms of a gene
– Dominant allele masks other
alleles
– Recessive allele is masked
• Gene = sequence of DNA that codes
for a protein, gives rise to physical
trait
Locus 1
Locus 2
Locus 3
Each sex cell will
carry only one allele
for each gene
W W
W
w
dominant allele
W W
Chromosomes
duplicate
w w
Pairs separate
Duplicates
separate
W
recessive allele
Separation of
Chromosome Pairs
W
w
w w
Duplicates
separate
w
Inheritance Pattern for One Gene
(for genes on pairs 1-22)
phenotype =
physical
characteristic
TT or Tt = no disease
tt = Tay-Sachs disease
Donald, no disease
Darla, no disease
Tt
T
t
homozygous
dominant
Tt
T
t
TT
Tt
Tt
tt
heterozygous
(carrier)
genotype = set
of alleles
Chances with each
pregnancy:
75% no disease
25% Tay-Sachs disease
homozygous
recessive
Molecular Basis for Effects of
Dominant and Recessive Alleles
• Dominant Allele
– codes for a functional protein
– eg. T allele gives instructions for making
Hexosaminidase A (Hex A), an enzyme involved in
lipid metabolism
• Recessive Allele
– codes for a non-functional protein or prevents any
protein product from being formed
– eg. with the t allele, no functional Hex A is detected
Variations in Genetic Patterns: Codominance
Neither allele masks the other so that effects
of both alleles are observed in heterozygotes
without blending
Example: ABO Blood Type
Alleles A and B are codominant.
Alleles A and B are completely dominant over o.
Type A
Type B
Type O
Blood Type
Genotypes
Type A
AA or Ao
Type B
BB or Bo
Type AB
AB
Type O
oo
Effects of both
alleles observed
in phenotype
Type AB
Variations in Genetic Patterns: Multiple Alleles
Three or more alleles exist for one trait
[Note: A person can only carry any two
of these alleles at once.]
Examples: ABO Blood Type
and also Rh Factor
Phenotype
Genotype*
Rh Positive
Rh Negative
RR or Rr
rr
Protein on Red
Blood Cells
Rhesus Protein
None
*Although there are multiple R alleles, R1, R2, R3, etc. all are
completely dominant over all of the r alleles, r1, r2, r3, etc.
ABO Blood Type and Rh Factor are controlled by
separate genes. They are inherited independently.
Variations in Genetic Patterns: Polygenic Inheritance
Many genes affect one trait
Example: Skin color
Number of Skin Color*
Dominant (Phenotype)
Alleles
0
White
Genotypes
% Pigmentation*
aabb
Aabb or aaBb
0-11%
1
Light Black
2
Medium Black AAbb or AaBb or
aaBB
26-40%
3
Dark Black
41-55%
4
Darkest Black AABB
AABb or AaBB
12-25%
56-78%
*Based on a study conducted in Jamaica.
Variations in Genetic Patterns:
Sex Influenced Genes
Genes that have different dominance
patterns in males and females
Example: Pattern Baldness
Caused by a dominant allele in males,
but a recessive allele in females
bb
BB or Bb
BB or Bb
bb
Inheritance for Sex-linked Genes
(for genes on pair 23)
Males carry only one copy of genes on the X chromosome
Females can be homozygous or heterozygous these genes
Hemophilic Male
Non-hemophilic
Female
Gramps
XhY
(father is hemophilic)
XhY
H = no hemophilia
h = hemophilia
Xh
x
XHXh
XH
XHXh
Xh
XhXh
XHY
XhY
Y
Chance for each pregnancy:
¼ non-hemophilic females; ¼ hemophilic females
¼ non-hemophilic males; ¼ hemophilic males
The Human Genome Project:
Genetic Differences at the DNA Level
Per 23
chromosomes
Now estimated
at 30,000
genes
Studying DNA
• Cut chromosomal DNA into smaller pieces
with restriction enzymes
Bam H1
5’— A A G T C G G A T C C T G A C G T— 3’
3’— T T C A G C C T A G G A C T G C A— 5’
Bam H1
Results in
separate fragments
sticky end
5’— A A G T C G
3’— T T C A G C C T A G
G A T C C T G A C G T— 3’
G A C T G C A— 5’
sticky end
Studying DNA
• Cut chromosomal DNA into smaller pieces
with restriction enzymes
• Separate DNA pieces by size using agarose
gel electrophoresis
DNA samples are placed in
an agarose gel
Electric current is applied
to separate DNA by size
UV light is used to detect a
fluorescent dye attached to
the DNA fragments
Example of a gel pattern
Agarose Gel Electrophoresis
larger
fragments
smaller
fragments
Studying DNA
• Transfer DNA to filter for analysis with probe
that will bind to specific sequence
DNA separated by size
is transferred from
agarose gel to filter
DNA pattern on filter will be identical to gel separation pattern.
Studying DNA
Probe: sequence of DNA that is
complementary to the sequence of
interest; Used to locate a copy of the
DNA sequence by hybridization
AGCTTAGCGAT
TCGAATCGCTA
Denature DNA by heating
Add Probe
Probe Binds to gene
AGCTTAGCGAT
AATCGC
TCGAATCGCTA
DNA Pattern on Gel
Pattern on Filter
after probe binding
Studying DNA
• Allow probe to bind to DNA on filter, visualize
region of probe attachment
DNA on filter is
exposed to probe
to detect
complementary
sequences.
Studying DNA
• Identify similarities and differences between
individuals– Paternity Testing
X
X
X
X
X
X
X
X
Studying DNA
• Identify patterns that are unique to specific
genes– Medical Genetic Testing
Testing for
Sickle Cell Alleles
On the basis of this analysis,
the genotype of the fetus is
1. AS
2. AA
3. SS
4. Unknown
Andrew Gobea
Treated for SCID
Severe Combined Immune Deficiency
Future Directions:
Gene Therapy
Ashanthi DeSilva