Download Prenatal Testing for Genetic Disorders

Biotechnology and Society
Chapter 14
Keep In Mind
 Recombinant DNA is DNA that has been
artificially created by incorporating DNA from 2
or more sources into a single recombinant
molecule
 Biotechnology
• The use of recombinant DNA technology to
produce commercial goods and services
Recombinant DNA
 Originally used to transfer foreign genes into
bacteria so that researchers could clone large
quantities of specific genes in order to study:
gene organization
gene function
gene regulation
Human Proteins
Can Be Made in Animals
 Transgenic
• The transfer of genes between species
 Transgenic organism
• An organism that has received a gene from
another species by means of recombinant DNA
technology
Biotechnology now used…
 to make pharmaceutical products in genetically
altered plants &animals
 to produce new varieties of agricultural plants &
animals
 to generated animal models for the study of
human diseases
 to diagnose & treat diseases
 to prepare DNA profiles used in forensic
applications and in other fields
Biopharming: Making Medical Molecules
in Animals and Plants
 Genetic engineering is used to manufacture
human proteins in bacteria and cell lines from
higher organisms (such animals and plants)
 These proteins are used in treating human
diseases
• Examples: Blood clotting factors for hemophiliacs,
insulin for diabetics
• Provides a constant supply, uncontaminated by
disease-causing agents (in the early 1980’s, 60%
of hemophiliacs became HIV positive due to
receiving contaminated blood serum)
Pompe Disease
 Pompe disease
• An inability to make α-glucosidase (GAA)
• Treated by enzyme replacement therapy
 Transgenic animals produce human GAA
• Transgenic female rabbits produce human GAA
enzyme in their milk
• The enzyme is purified from collected milk and
given to patients intravenously (also use
hamsters!)
More on Biopharming
 Crop plants such as corn and bananas are being
investigated as sources of edible vaccines
 Trials of a vaccine against bacterial diarrhea eating uncooked potatoes
 Future? Hepatitis & diphtheria vaccines in
bananas?
Genetically Modified Foods
 Genetically modified organisms (GMOs)
• A term referring to transgenic plants or animals
 60% to 70% of foods in US supermarkets
contain some transgenic plant material
 Products made from corn, soybeans, cottonseed
and canola oils most commonly contain
transgenic ingredients
14.2 Genetically Modified Foods
Artificial selection has been used by farmers for
years to improve yield & nutritional value of their
crops. (modern corn to ancestral maize)
Today…
 Gene transfer into crop plants confers resistance
to herbicides, insect pests, and plant diseases
 Also used to increase the nutritional value of
foods (such as vitamin A)
Herbicide Resistance & Bt crops
 Herbicide-resistant crops (resistant to broadspectrum herbicides)
 herbicides kill all plants in the field except the crops &
the herbicides break down quickly in the soil
 Bt crops carry a bacterial gene that produces a
toxin; insects eat part of the plant, the toxin is
released in the gut of the insect –DIE BUG!!
 Farmers use less pesticide & herbicide – save money,
protect environment!
Transgenic Crops
Used to Enhance Nutrition
 Vitamin A deficiency is a serious health issue in
over 70 countries (primarily in Asia)
 ~500,000 children become permanently blind
every year due to Vitamin A deficiency in their
diets
 Golden rice increases vitamin A
• Genes from daffodils, corn, and bacteria allow the
rice to produce beta-carotene (Vitamin A
precursor)
Concerns About
Genetically Modified Organisms
 Are foods containing new proteins safe to eat?
 Is it safe to eat food carrying part of a viral gene
that switches on transgenes?
 Will pesticide-resistant insects develop?
 Will disease-causing bacteria acquire antibioticresistance genes used as markers?
14.3 Transgenic Animals
as Models of Human Diseases
Mouse models of human diseases
 Transfer of disease-causing human genes into
mice creates transgenic organisms that are used
to
produce an animal with symptoms that mirror
those in human
study the development & progress of the
diseases and
test the effects of drugs and other therapies as
methods of treating these disorders
Huntington Disease Mice as Models
 HD mice are extremely useful as models of
human neurodegenerative disorders
• Used to study the progressive destruction of brain
structures in early disease stages
• Used to link changes in brain structure with
changes in behavior
• Used to screen drugs to improve symptoms or
reverse brain damage
Transferring Genes into Mammals
To make a transgenic HD mouse…
 copies of the mutant HD gene were cloned into
vectors
 the vectors carrying the HD gene were
microinjected into the nucleus of a fertilized
mouse eggs
 the eggs were implanted into surrogate mothers
who gave birth to transgenic mice with the
mutant HD gene
14.4 Testing for Genetic Disorders
 Genetic testing
• Used to determine if someone has a genotype for
a genetic disorder or is a carrier
• Identifies individuals with a particular genotype
• Usually a matter of choice to be tested
 Genetic screening
• Systematic search for individuals in a population
where there is a risk for a particular disorder (in
other words – everyone in the population is tested
• Often is mandated by law
Four Types of Testing Programs
 Newborn screening
 Carrier testing
 Prenatal testing
 Presymptomatic (predictive) testing
Newborn Screening in the US
 Newborn screening tests infants within 48 to 72
hours after birth for a variety of genetically
controlled metabolic disorders
 All states require newborns to be tested
• Most states screen for 3 to 8 disorders (ex: PKU
& galactosemia)
• New methods can scan for 30 to 50 disorders
Carrier Testing for Genetic Disorders
 Carrier testing searches for heterozygotes that
may be at risk of producing a child with a genetic
disorder
• Done on family members, or cultural groups, with
a history of a genetic disorder such as sickle cell
anemia or cystic fibrosis
Prenatal Testing for Genetic Disorders
 Prenatal testing tests a fetus for genetic
disorders (e.g. cystic fibrosis, Tay Sacs, ) or
chromosome abnormalities (e.g. Down
syndrome)
In most cases, testing is done only when there is
a family history or some other indication, like
advanced maternal age, points to risk for the
fetus having a genetic disorder
Methods of Prenatal Testing
Risks to mother & fetus include
 Amniocentesis can be done after the 15th week
of development
risk of miscarriage: 0.5% to 1%
 Chorionic villus sampling (CVS) is usually done
at 10 to 12 weeks of development
risk of miscarriage: 1% to 3%
Prenatal Testing
Can Diagnose Sickle Cell Anemia
Recombinant DNA-based prenatal testing can
detect genetic disorders that cannot otherwise
be detected before birth
 Sickle-cell beta globin genes have a distinctive
pattern of banding on a Southern blot
• Normal gene: Two small fragments
• Sickle gene: One large fragment
Prenatal Testing using Recombinant DNA
 Recombinant DNA-based prenatal testing can
detect genetic disorders that cannot otherwise
be detected before birth; techniques include…
 Southern blot analysis
testing can be done on blastomeres from in vitro
fertilization, before embryo is implanted
polar body biopsy before egg is fertilized in vitro
Presymptomatic Testing
Can Be Done for Some Genetic Disorders
 Presymptomatic testing (predictive testing)
identifies some individuals who will develop
adult-onset genetic disorders; ex:
Genetics in Society:
Who Owns a Genetic Test?
 Families of children with Canavan disease, a
rare and fatal disorder, started a foundation to
obtain tissue samples and funding for research
 The research hospital patented the gene and
charged participating families for the test
 After a lawsuit, the hospital was allowed to
continue to license the test and collect royalties
14.5 DNA Microarrays in Genetic Testing
 Testing for a wide range of genetic disorders is
possible using DNA chips (microarrays), which
can hold thousands of genes
 http://learn.genetics.utah.edu/content/labs/micro
array/
 DNA microarray
• A series of short nucleotide sequences placed on
a solid support (such as glass) that have several
different uses
Uses of Microarray Technology
 Detecting mutant genes
• Individuals who will develop late-onset genetic
disorders such as polycystic kidney disease
(PCKD) and Huntington disease
• Individuals at risk for disorders such as diabetes
 Detecting differences in the pattern of gene
expression in normal and cancerous cells
Microarray Testing
 Each field of the microarray contains a unique
sequence of single-stranded DNA
 Test DNA and normal DNA are converted to
single strands, tagged with fluorescent dyes, and
hybridized to the chip
 Each result has a different color
• Normal alone is green; mutant alone is red
• Both together are yellow; a blank field is black
14.6 DNA Profiles & DNA Fingerprints as
Tools for Identification
 DNA profiles (& DNA fingerprints) use variations
in the length of short repetitive DNA sequences
(STRs = short tandem repeats) to identify
individuals with a high degree of accuracy and
reliability
http://www.teachersdomain.org/asset/tdc02_int_cre
atednafp2/
 This method is used in many areas, including
law enforcement, biohistory, conservation, and
the study of human populations
DNA Profiles Can Be Made from
Short Tandem Repeats (STRs)
 STRs range from 2 to 9 base pairs in length
• CCTTCCCTTCCCTTCCCTTCCCTTCCCTTC
contains six repeats of the CCTTC sequence
 Repeat numbers vary between individuals
• A unique profile can be produced by analyzing
several STRs in a DNA sample
• In the US, a standard set of 13 STRs (CODIS) is
used to prepare a profile
DNA Profiles Are Used in the Courtroom
 Analysis of DNA profiles combines probability
theory, statistics, and population genetics to
estimate how frequently an allele combination is
found in a population
 Population frequencies for STRs are multiplied
together to produce an estimate
Genetic Journeys: Death of a Czar
 Forensics and several types of DNA evidence
were used to confirm that bones discovered in
1991 belonged to Czar Nicholas Romanov II, his
wife, and three of their five children
14.7 Social and Ethical
Questions about Biotechnology
 Applications of recombinant DNA technology
have developed faster than societal consensus,
public policy, and laws governing its use
 Efforts to inform legislators, members of the
legal and medical profession, and the public
often have lagged behind its commercial use
• A balanced approach requires education and
debates on risks and benefits
Keep In Mind
 The uses of biotechnology have produced
unresolved ethical issues