Understanding Human Genetic Disorders

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Understanding Human Genetic Disorders Karen G.
Hales, PhD Associate Professor of
Biology Davidson College
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A typical cell
http//probes.invitrogen.com/handbook/figures/0908
.html
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Chromosomes and DNA
A
T
T
A
G
C
G
C
http//publications.nigms.nih.gov/thenewgenetics/c
hapter1.htmlc1
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DNA sequences
Chromosome 7
21 million bases
.GTGCCACCTCATCAACCATTCTCGTGTAAACAGACAGAATTTACCTT
TTGCACTCATAATCTCATGATTGTGTATTTCACTTTCCTCCATTTCCTTG
GATATTTCGTTGTTTTGACTTGTTTGGCATGTGCAGCCGTGGTAGTGCTA
.
130 million bases
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A twenty-three volume instruction manual
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The instruction manual stays in the nucleus
What is a gene?
What is a protein?

http//probes.invitrogen.com/handbook/figures/0908
.html
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Different types of cells
intestinal cells
http//mednote.co.kr/images/epithsurf.jpg
neuron
blood cells
muscle cells
http//www.infovisual.info/03/041_en.html
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Gene sequence within DNA
A T G G A T C T T C G A
G C A
T A C C T A G A A G C T
C G T
RNA (photocopy of gene)
A U G G A U C U U C G A
G C A
resulting protein
met asp leu arg
ala
sequence of amino acids determines folding and
function
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The genetic code
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RNA
A U G G A U C U U C G A
G C A
met asp leu arg
ala
if there's a typo
A U G G A U C A U C G A
G C A.
met asp his arg
ala
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Genetic disorders
The protein encoded by the cystic fibrosis gene
no functional protein
from Griffiths et al, 1998, Modern Genetic
Analysis.
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Sickle cell anemia
medicine.osu.edu
www.nhlbi.nih.gov/.../Sca/SCA_WhatIs.html
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Hemoglobin is defective in sickle cell anemia
Purves et al., 2006, Life The Science of Biology
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Alzheimers disease
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outside brain cell
build-up of this causes Alzheimers
inside brain cell
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Deafness
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Close up of Organ of Corti
http//genet.annualreviews.org/content/vol35/issue
1/images/large/ge35_0589_1.jpeg
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Dwarfism-- achondroplasia
normal
typo on page 7225
http//seattlepi.nwsource.com/local/200937_lawprof
24.html?sourcerss
http//gallery.fansites.com /showpic.asp?FN1010Tr
oyer_Verne002
http//www.villagevoice.com/news/0436,mcnulty,5654
3,1.htmlhttp//seattlepi.nwsource.com/local/200937
_lawprof24.html?sourcerss
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Bone development endochondral ossification
From Gilbert, Developmental Biology, 6th edition,
2000.
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X chromosome linked disorders Hemophilia Muscul
ar dystrophy
typo on page 248
typo on page 248
healthy
sick
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Gene therapy
--Viruses as carriers for DNA --ex vivo vs. in
vivo approaches --Practical limitations
http//gslc.genetics.utah.edu/units/genetherapy/gt
challenges/
From Lewis, R. Human Genetics Concepts and
Applications, 2000.
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Recent advances in gene therapy
Muscular dystrophy dystrophin Parkinsons
glutamic acid decarboxylase to produce
GABA Macular degeneration pigment
epithelium-derived factor to inhibit blood vessel
growth Cancer add gene to T cells to make
them attack melanoma