Transcript Chapter 14 Human Genetics - Hollidaysburg Area School

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Scientists know much less about human
inheritance than they do about other
organisms.
Model organisms are the fruit fly and mice.
With this new understanding, scientists must
study genetics carefully. WHY?
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In each of our somatic cells, we have 44 autosomes and
2 sex chromosomes (23 pairs of chromosomes)
In order to study our chromosomes, biologists
photograph cells when they are in mitosis (metaphase).
A karyotype is a picture of the chromosomes when they
are grouped together in pairs.
Normal females have 46,XX notation and normal
males have 46,XY notation.
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A normal egg cell is 23,X. A normal sperm cell is either 23,X
or 23,Y.
1. Cells are grown (in a cell culture dish) to increase their number.
2. Cell division is then stopped in metaphase. (Why metaphase?)
3. Cells are centrifuged and lysed to release chromosomes.
4. Chromosomes are stained, photographed, and grouped by size
and banding patterns.
“p” = shorter arm above centromere
“q” = longer arm below centromere
 A normal egg cell is 23,X. A normal sperm cell is
either 23,X or 23,Y.
 Gender is determined by inheritance of either XX
or XY. So, we can say that the male determines
the sex of a child.
 Genetic differences (3:52)
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A pedigree chart is used to show how a trait is
passed from one generation to the next.
In a pedigree, a circle represents a female and
a square represents a male.
A colored square or circle means that person
has the trait, while a non-colored square or
circle means that person does not have the
trait.
Some of the most obvious traits are impossible to
trace to a single gene. This is due to two main
reasons:
1. They are polygenic.
2. Many traits are influenced by the environment.
For example, improved health practices since the
1800s in the U.S. has caused greater height.
 Environmental effects are not inherited.
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Our complete set of
genetic information is
called the human
genome.
 Studying the human
genome has taken
much longer than other
organisms because
humans have a long
generation time,
complex life cycle, and
produce few offspring.
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For many disorders scientists do not know the link between
DNA and the disorder.
 The link for cystic fibrosis and sickle cell disease is
understood
 The small change in the DNA of one gene affects the
structure of a protein – this causes the disorder.
Lysosomal Disease (2:09)
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Depends on the gene’s
protein product and its role
in the cell
Cystic fibrosis – one copy
of the normal allele
provides enough proteins
to function
 Normal allele is dominant
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over the recessive
Huntington’s – one copy of
the normal allele is not
enough, so the disorder
allele is dominant over the
normal allele
 Y chromosome is smaller
than the X, therefore it has
fewer genes.
 Males have only one X
chromosome, so all X-linked
alleles are expressed in males
 If a disorder is recessive,
females must have two copies
of the allele because they have
two X chromosomes.
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Colorblindness: far more common in males
 Said to be X-linked, meaning that the allele is only
present on the X chromosome
 Since males only have one X chromosome, they only
need one copy of the recessive allele to have
colorblindness, whereas females need two copies.
Hemophilia, Duchenne muscular dystrophy
Does Dad have the
disease?
What about Mom?
Probability that a
daughter will inherit?
Probability that a son
will inherit?
Females need to adjust to the extra X allele.
British geneticist Mary Lyon discovered that
one X chromosome is randomly switched off.
 The switched off chromosome forms a dense
region in the nucleus called the Barr body.
 Normally not found in males
 Reason for color in calico cats
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In meiosis, chromosomes separate.
 If this fails to work properly, errors occur
Nondisjunction – most common error
 When homologous chromosomes fail to separate
 Abnormal number of chromosomes finds its way
into gametes
 Trisomy 13, 18, and 21
Trisomy 13 – Patau Syndrome (47,XY,+13)
Trisomy 18 – Edward’s Syndrome
(47,XY,+18)
Serious eye, brain,
Almost every organ
circulatory defects
system affected; 1:6000
as well as cleft
live births. Children
palate; 1:15,000 live
with full Trisomy 18
births; children
generally do not live
rarely live more than
more than a few
a few months
months.
Trisomy 21 - Down Syndrome (47,XY,+21)
47,XYY
Klinefelter Syndrome (47,XXY)
Male sex organs present, but sterile;
breast enlargement and other feminine
body characteristics; normal
intelligence; 1:750 live male births
Somewhat taller than average and often
have below normal intelligence; at one time
(~1970s), it was thought that these men
were likely to be criminally aggressive, but
this hypothesis has been proven false;
1:1000 live male births
Turner’s Syndrome (45,XO)
Trisomy X 47,XXX
1:1000 live female births; healthy and
fertile; often cannot be distinguished from
normal female except by karyotype
1:2500 live female births; do not mature
sexually during puberty and are sterile;
short stature and normal intelligence
Until recently we could
not modify the genetic
code (genome).
 Scientists use their
knowledge of the
structural and chemical
properties of DNA to
study and change it
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We have the technology
to extract DNA from cells,
to cut DNA into smaller
pieces, and to identify the
sequence of bases
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No two individuals are exactly genetically alike.
DNA fingerprinting analyzes sections of DNA that vary
widely from person to person
DNA separated into series of bands
Useful in convictions (first used in England, 1986)
Samples can be taken from blood, hair, and bodily fluids
It’s easy to see in this example that daughter
2 is the child from the mother’s previous
marriage and son 2 is adopted. You can see
that both daughter 1 and son 1 share RFLPs
with both the mom and dad, while daughter 2
has RFLPs of the mom but not the dad, and
son 2 does not have RFLPs from either
parent, so he must have been _____.
Fingerprinting FUN!
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Sequencing of the entire human genome
Started in 1990 and finished in 2003
Cost to American taxpayers? $3.8 billion
Project goals:
 Identify all the approximately 20,000-25,000 genes in
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human DNA and determine the sequences of the 3.1
billion base pairs that make up human DNA
Store this information in databases
Improve tools for data analysis
Transfer related technologies to the private sector
Address the ethical, legal, and social issues (ELSI) that
may arise from the project.
Genome Video (24:20)
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How do we get DNA out of cells?
Three basic steps:
 Break cells open and remove the membranes
 Remove proteins from the DNA using salt
 Add ethanol – DNA is not soluble in ethanol so it
clumps together
Gene Therapy: An absent or faulty gene is replaced
by a normal working one.
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How does it work?
1. Body cells with the defective gene are isolated
2. A copy of the normal gene is inserted into viruses
3. The isolated cells are "infected" with these
modified viruses
4. The viral DNA which carries the normal gene
inserts itself into the host DNA
5. The host cells that now contain the new DNA are
cloned in the lab
6. These new cultured cells are injected into the
patient
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When has it been successful?
 Scientists have seen some success in the following:
▪ Inherited blindness
▪ Sickle cell disease
▪ Cystic fibrosis
▪ Some cancers (leukemia, lymphoma, myeloma)
▪ Parkinson’s disease
▪ Huntington’s disease
▪ SCID (severe combined immunodeficiency)
▪ Deafness in guinea pigs
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Limitations & Problems
1. The treatment may only be temporary
2. Patient has an immune response to the virus
3. Virus may regain its ability to cause disease
4. The therapy must target specific cells
5. Usually cannot reverse damage already done to
body systems
6. The cost for just one treatment can be well over
$100,000 (and insurance doesn’t cover it)
Gene Therapy Success (3:34)
What is Gene Therapy? (15:27)
This one might hurt your brain!