A review of the section and why we use pedigree analysis to address genetic diseases in humans.

1. Pedigree Analysis

2. Classical Genetics
• Mendelian inheritance describes
inheritance patterns that obey two laws
– Law of segregation
– Law of independent assortment
• Simple Mendelian inheritance involves
– A single gene with two different alleles
– Alleles display a simple dominant/recessive
relationship

3. • Consider, for example, the traits that Mendel studied
Wild-type (dominant) allele Mutant (recessive) allele
Purple flowers White flowers
Axial flowers Terminal flowers
Yellow seeds Green seeds
Round seeds Wrinkled seeds
Smooth pods Constricted pods
Green pods Yellow pods
Tall plants plants
• Another example is from Drosophila
Wild-type (dominant) allele Mutant (recessive) allele
Red eyes White eyes
Normal wings Miniature wings

4. • Human genetic diseases caused by
recessive mutant alleles
– The mutant alleles do not produce fully
functional proteins

5. Lethal Alleles
• Essential genes are those that are
absolutely required for survival
– The absence of their protein product leads to a
lethal phenotype
• It is estimated that about 1/3 of all genes are
essential for survival
• Nonessential genes are those not
absolutely required for survival
• A lethal allele is one that has the potential
to cause the death of an organism
– These alleles are typically the result of
mutations in essential genes
– usually recessive, but can be dominant

6. Lethal Alleles
• Many lethal alleles prevent cell division
• Some lethal allele exert their effect later in life
– Huntington disease
• Characterized by progressive degeneration of the nervous
system, dementia and early death
• The age of onset of the disease is usually between 30 to 50
• Conditional lethal alleles may kill an organism only
when certain environmental conditions prevail
– Temperature-sensitive (ts) lethals
• A developing Drosophila larva may be killed at 30 C
• But it will survive if grown at 22 C

7. • Every gene carries information telling the
body how to make a particular protein.
– Adult cells have two copies of each gene.
– If one copy of the gene doesn’t work, the cell
has a backup.
• New versions of genes can be produced by
mutations
– These new alleles can produce proteins that
either
• Do not work
• Or do something they’re not supposed to
• Thus any condition associated with this is
referred to as a genetic disease

8. • Cystic fibrosis (CF)
– A recessive disorder of humans
– About 3% of caucasians are carriers
– The gene encodes a protein called the cystic
fibrosis transmembrane conductance
regulator (CFTR)
• The CFTR protein regulates ion transport across
cell membranes
– The mutant allele creates an altered CFTR
protein that ultimately causes ion imbalance
• This leads to abnormalities in the pancreas, skin,
intestine, sweat glands and lungs

9. Example: Cystic fibrosis
The cell membranes of the cells lining the lungs and air
passages contain CF membrane proteins
Cl-
Cl-
Cell membrane Cl- CF membrane
proteins
Cl-
The CF protein pumps chloride ions from one side of the
membrane to the other

10. The CF protein produces a higher concentration of chloride
ions on one side of the membrane than the other
Cl- H2O
Cl-
Cl-
Cl-
H2O Cl- H2O
Cell membrane Cl- H2O
H2O
Cl-
H2O
Water molecules follow the chloride ions across the semi-
permeable cell membranes by… …osmosis.

11. The body uses the CF chloride pump to move water into
secretions like the mucus found in the trachea and sweat.
If your cells cannot make working chloride pumps, your
mucus becomes too thick and sticky due to lack of water
However, to make a functioning chloride pump, each cell
only needs one good copy of the gene for it.
So, cystic fibrosis is recessive

12. c C
Defective gene Healthy gene
produces non-working produces working
chloride pump chloride pump Cl -
Cl- Cl- Cl-
Cl- Cl- Cl-
Cl-
Cl- Cl-
Cl- This individual does not
suffer from cystic fibrosis,
but is a carrier

13. Neither copy of the
gene carried by this
individual can c c
produce a working
chloride pump
Cl-
Cl-
Cl -
Cl-
Cl-
This individual will
Cl -
Cl-
Cl- suffer from cystic
Cl- Cl-
fibrosis
REMEMBER: Genes do NOT exist to cause disease…
… defective genes cause disease

14. Pedigree Analysis
• In the study of human traits, there are
not controlled parental crosses
• Rely on information from family trees
or pedigrees
• Pedigree analysis is used to determine
the pattern of inheritance of traits in
humans

15. Pedigree
Symbols
Figure 2.10

16. Pedigree Analysis
• Pedigree analysis is commonly used to
determine the inheritance pattern of human
genetic diseases
• Genes that play a role in disease may exist as
– A normal allele
– A mutant allele that causes disease symptoms
• Disease that follow a simple Mendelian pattern
of inheritance can be
– Dominant
– Recessive

17. • A recessive pattern of inheritance makes
two important predictions
– 1. Two normal heterozygous individuals will
have, on average, 25% of their offspring
affected
– 2. Two affected individuals will produce
100% affected offspring
• A dominant pattern of inheritance
predicts that
– An affected individual will have inherited the
gene from at least one affected parent
– Alternatively, the disease may have been
the result of a new mutation that occurred
during gamete formation

18. Figure 2.10