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Human Genetic Diseases 1 2 AP Biology 2006-2007 3 4 5 6
Human Genetic Diseases
1
2
AP Biology
2006-2007
3
4
5
6
Pedigree analysis  Pedigree analysis reveals Mendelian patterns in human inheritance  data mapped on a
Pedigree analysis
 Pedigree analysis reveals Mendelian
patterns in human inheritance
 data mapped on a family tree
= male
= female
= male w/ trait
= female w/ trait

AP Biology

Simple pedigree analysis What’s the likely inheritance pattern? 1 2 1 2 3 3 4 4
Simple pedigree analysis
What’s the
likely inheritance
pattern?
1
2
1
2
3 3
4 4
5 5
6 6
AP Biology
Genetic counseling  Pedigree can help us understand the past & predict the future  Thousands
 
   

Genetic counseling

Pedigree can help us understand the past & predict the future

Thousands of genetic disorders are inherited as simple recessive traits

from benign conditions to deadly diseases

albinism cystic fibrosis Tay sachs sickle cell anemia PKU

AP Biology

Genetic testing
Genetic testing

sequence

individual

genes

AP Biology

 Heterozygotes (Aa)
 
 

Heterozygotes (Aa)

Recessive diseases

The diseases are recessive because the allele codes for either a malfunctioning protein or no protein at all

carriers

have a normal phenotype because one “normal” allele produces enough of the required protein

AP Biology

female / eggs

 

Heterozygote crosses

 
 

Heterozygotes as carriers of recessive alleles

Aa

x

Aa

male / sperm

Aa
Aa

A

 
 

a

A

a

AA AA
AA
AA
Aa Aa carrie
Aa
Aa
carrie

r

Aa Aa carrie
Aa
Aa
carrie
aa aa diseas
aa
aa
diseas

r

e

Aa
Aa
  • A

  • a

  • A

  • a

AP Biology

Cystic fibrosis (recessive)  Primarily whites of European descent  strikes 1 in 2500 births 
Cystic fibrosis (recessive)
 Primarily whites of
European descent
 strikes 1 in 2500 births
 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 2 O across cell membrane thicker & stickier mucus coats around cells mucus build-up in the pancreas, lungs, digestive tract & causes bacterial infections

AP Biology

without treatment children die before 5; with treatment can live past their late 20s

Chloride channel

Effect on Lungs

transports salt through protein channel out of cell Osmosis: H 2 O follows Cl

Chloride channel Effect on Lungs transports salt through protein channel out of cell Osmosis: H O
airway C l – Cl – channel H 2 O cells lining lungs C l –
airway
C
l
Cl – channel
H 2 O
cells lining
lungs
C
l
H 2 O
AP Biology
AP Biology
thickened mucus hard to secrete
thickened mucus
hard to secrete

normal

Chloride channel Effect on Lungs transports salt through protein channel out of cell Osmosis: H O

lungs

cystic

Chloride channel Effect on Lungs transports salt through protein channel out of cell Osmosis: H O

fibrosis

bacteria & mucus build up

Chloride channel Effect on Lungs transports salt through protein channel out of cell Osmosis: H O

mucus secreting glands

delta F508 loss of one amino acid AP Biology
delta
F508
loss of
one
amino
acid
AP Biology
   
 

strikes 1 in 3600 births

Tay-Sachs (recessive)

Primarily Jews of eastern European (Ashkenazi) descent & Cajuns (Louisiana)

100 times greater than incidence among non-Jews

non-functional enzyme fails to breakdown lipids in brain cells

AP Biology

fats collect in cells destroying their function symptoms begin few months after birth seizures, blindness & degeneration of muscle & mental performance child usually dies before 5yo

 strikes 1 in 3600 births Tay-Sachs (recessive)  Primarily Jews of eastern European (Ashkenazi) descent
 Primarily Africans  high frequency
 
 

Primarily Africans

high frequency

Sickle cell anemia (recessive)

strikes 1 out of 400 African Americans

caused by substitution of a single amino acid in hemoglobin

when oxygen levels are low, sickle-cell hemoglobin crystallizes into long rods

deforms red blood cells into sickle shape

sickling creates pleiotropic effects = cascade of other symptoms

AP Biology

 Primarily Africans  high frequency Sickle cell anemia (recessive)  strikes 1 out of 400

Sickle cell anemia

 Substitution of one amino acid in polypeptide chain
 Substitution of one amino acid in
polypeptide chain

AP Biology

hydrophilic amino acid

hydrophobic amino acid

AP Biology

AP Biology

 2 alleles are codominant
 
 

2 alleles are codominant

Sickle cell phenotype

both normal & mutant hemoglobins are synthesized in heterozygote (Aa) 50% cells sickle; 50% cells normal carriers usually healthy sickle-cell disease triggered under blood oxygen stress

exercise

 2 alleles are codominant Sickle cell phenotype  both normal & mutant hemoglobins are synthesized

AP Biology

 Malaria Heterozygote advantage  single-celled eukaryote parasite spends part of its life cycle in red
   
 

Malaria

Heterozygote advantage

single-celled eukaryote parasite spends part of its life cycle in red blood cells

In tropical Africa, where malaria is common:

homozygous dominant individuals die of malaria

homozygous recessive individuals die of sickle cell anemia

heterozygote carriers are relatively free of both

 Malaria Heterozygote advantage  single-celled eukaryote parasite spends part of its life cycle in red

reproductive advantage

High frequency of sickle cell allele in African Americans is vestige of African roots

AP Biology

Prevalence of Malaria
Prevalence of Malaria

Prevalence of Sickle Cell Anemia

AP Biology
AP Biology
Prevalence of Malaria Prevalence of Sickle Cell Anemia AP Biology
 Dominant inheritance  repeated mutation on end of chromosome 4 Testing… Would you  mutation
 Dominant inheritance
 repeated mutation on end of
chromosome 4
Testing…
Would you
 mutation = CAG repeats
 glutamine amino acid repeats in protein
 one of 1 st genes to be identified
want to
know?
 memory loss
 muscle tremors, jerky movements
 “chorea”
 starts at age 30-50
 early death
 10-20 years after start
AP Biology

Huntington’s chorea (dominant)

1872
1872

build up of “huntingtin” protein in brain causing cell death

Genetics & culture  Why do all cultures have a taboo against incest?  laws or
 
   

Genetics & culture

Why do all cultures have a taboo against incest?

laws or cultural taboos forbidding marriages between close relatives are fairly universal

Fairly unlikely that 2 unrelated carriers of same rare harmful recessive allele will meet & mate

AP Biology

but matings between close relatives increase risk “consanguineous” (same blood) matings individuals who share a recent common ancestor are more likely to carry same recessive alleles

Genetics & culture  Why do all cultures have a taboo against incest?  laws or
A hidden disease reveals itself AA x Aa Aa x Aa male / sperm male /
A hidden disease reveals itself
AA
x
Aa
Aa
x
Aa
male / sperm
male / sperm
A
A
A
a
AA
AA
AA
AA
Aa
Aa
A
A
a
a
Aa
Aa
Aa
Aa
aa
aa
AP Biology
• increase carriers in population
• hidden disease is revealed
female / eggs
female / eggs
Any questions?
Any questions?

AP Biology

2006-2007

Ghosts of Lectures Past (storage)
Ghosts of Lectures Past
(storage)

AP Biology

2006-2007

   
 

Sickle cell frequency

1 out of 400 African Americans

Heterozygote advantage

high frequency of heterozygotes is unusual for allele with severe detrimental effects in homozygotes

Suggests some selective advantage of being heterozygous

sickle cell: resistance to malaria? cystic fibrosis: resistance to cholera?

AP Biology

Malaria

AP Biology
AP Biology
Malaria AP Biology
Malaria AP Biology
Woody Guthrie & Arlo Guthrie AP Biology

Woody Guthrie & Arlo Guthrie

Woody Guthrie & Arlo Guthrie AP Biology

AP Biology