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Division Ave. High School
Ms. Foglia
AP Biology
Human Genetic Diseases
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AP Biology
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2006-2007
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Pedigree analysis
n Pedigree analysis reveals Mendelian
patterns in human inheritance
u data mapped on a family tree
= male
= female
= male w/ trait
= female w/ trait
AP Biology
Simple pedigree analysis
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33
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What’s the
likely inheritance
pattern?
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55
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Division Ave. High School
Ms. Foglia
AP Biology
Genetic counseling
n Pedigree can help us understand the past
& predict the future
n Thousands of genetic disorders are
inherited as simple recessive traits
u from benign conditions to deadly diseases
albinism
cystic fibrosis
n Tay sachs
n sickle cell anemia
n PKU
n
n
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Genetic testing
sequence
individual genes
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Recessive diseases
n The diseases are recessive because the
allele codes for either a malfunctioning
protein or no protein at all
u
Heterozygotes (Aa)
n
n
carriers
have a normal phenotype because one
“normal” allele produces enough of the
required protein
AP Biology
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Division Ave. High School
Ms. Foglia
AP Biology
Heterozygote crosses
n Heterozygotes as carriers of recessive alleles
Aa x Aa
A
Aa
male / sperm
female / eggs
A
AA
AA
A
Aa
Aa
carrier
Aa
Aa
a
a
a
carrier
A
Aa
aa
a
disease
AP Biology
Cystic fibrosis (recessive)
n Primarily whites of
European descent
u
strikes 1 in 2500 births
n
u
n
n
n
u
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1 in 25 whites is a carrier (Aa)
normal lung tissue
normal allele codes for a membrane protein
that transports Cl- across cell membrane
defective or absent channels limit transport of Cl- & H 2O
across cell membrane
thicker & stickier mucus coats around cells
mucus build-up in the pancreas, lungs, digestive tract &
causes bacterial infections
without treatment children die before 5;
with treatment can live past their late 20s
Chloride channel
Effect on Lungs
normal lungs
airway
Cl–
transports salt through protein
channel out of cell
Osmosis: H 2O follows Cl–
Cl– channel
H 2O
cells lining
lungs
cystic fibrosis
Cl–
H 2O
bacteria & mucus build up
thickened mucus
hard to secrete
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mucus secreting glands
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Division Ave. High School
Ms. Foglia
AP Biology
delta F508
loss of one
amino acid
AP Biology
Tay-Sachs (recessive)
n
Primarily Jews of eastern European (Ashkenazi)
descent & Cajuns (Louisiana)
u strikes 1 in 3600 births
n
u
non-functional enzyme fails to breakdown lipids
in brain cells
n
fats collect in cells destroying their function
n
symptoms begin few months
after birth
seizures, blindness &
degeneration of muscle &
mental performance
child usually dies before 5yo
n
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100 times greater than incidence among
non-Jews
n
Sickle cell anemia (recessive)
n
Primarily Africans
u
strikes 1 out of 400 African Americans
n
high frequency
caused by substitution of a single amino
acid in hemoglobin
u when oxygen levels are low, sickle-cell
hemoglobin crystallizes into long rods
u
deforms red blood cells into
sickle shape
n sickling creates pleiotropic
effects = cascade of other
symptoms
n
AP Biology
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Division Ave. High School
Ms. Foglia
AP Biology
Sickle cell anemia
n Substitution of one amino acid in
polypeptide chain
hydrophilic
amino acid
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hydrophobic
amino acid
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Sickle cell phenotype
n 2 alleles are codominant
both normal & mutant hemoglobins are
synthesized in heterozygote (Aa)
u 50% cells sickle; 50% cells normal
u carriers usually healthy
u sickle-cell disease
triggered under blood
oxygen stress
u
n
exercise
AP Biology
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Division Ave. High School
Ms. Foglia
AP Biology
Heterozygote advantage
n Malaria
single-celled eukaryote parasite spends part of its
life cycle in red blood cells
n In tropical Africa, where malaria is common:
u homozygous dominant individuals die of malaria
u homozygous recessive individuals die of sickle cell
anemia
u heterozygote carriers are relatively free of both
u
n
reproductive advantage
n High frequency of sickle
cell allele in African
Americans is vestige of
African roots
AP Biology
Prevalence of Malaria
Prevalence of Sickle
Cell Anemia
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Huntington’s chorea (dominant)
n Dominant inheritance
u
Testing…
Would you
want to
know?
u
AP Biology
1872
repeated mutation on end of
chromosome 4
n
mutation = CAG repeats
n
glutamine amino acid repeats in protein
n
one of 1 st genes to be identified
build up of “huntingtin” protein in brain causing cell
death
n
memory loss
n
muscle tremors, jerky movements
w “chorea”
n
starts at age 30-50
n
early death
w 10-20 years after start
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Division Ave. High School
Ms. Foglia
AP Biology
Genetics & culture
n Why do all cultures have a taboo against incest?
laws or cultural taboos forbidding marriages
between close relatives are fairly universal
n Fairly unlikely that 2 unrelated carriers of same
rare harmful recessive allele will meet & mate
u but matings between close relatives increase risk
n “consanguineous” (same blood) matings
u individuals who share a
recent common ancestor
are more likely to carry
same recessive alleles
u
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A hidden disease reveals itself
Aa
AA x Aa
A
AA
AA
a
Aa
Aa
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female / eggs
female / eggs
A
Aa
male / sperm
male / sperm
A
x
A
a
A
AA
Aa
a
Aa
aa
• increase carriers in population
• hidden disease is revealed
Any questions?
AP Biology
2006-2007
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Division Ave. High School
Ms. Foglia
AP Biology
Ghosts of Lectures Past
(storage)
AP Biology
2006-2007
Heterozygote advantage
n
Sickle cell frequency
u
high frequency of heterozygotes
is unusual for allele with severe
detrimental effects in homozygotes
n
n
1 out of 400 African Americans
Suggests some selective advantage of
being heterozygous
u
sickle cell: resistance to malaria?
u
cystic fibrosis: resistance to cholera?
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Malaria
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Division Ave. High School
Ms. Foglia
AP Biology
Woody Guthrie & Arlo Guthrie
AP Biology
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