Transcript Classic Methods of Genetic Analysis

Classic Methods of Genetic
Analysis
1.Isolation of mutants and experimental crosses to
see inheritance patterns
2.Organism of study: bacteria, viruses, fruit flies,
and mice
– a.Short life cycle, lots of offsprings
3.Do not work for humans:
– a.Ethics
– b.Long life cycle, few offsprings
– c.Use alternative methods
Genetic Counseling
• Done at most major hospitals
• Visit counselor if you have relatives or
children with a genetic disorder or have
had a baby die or been still born
• Deals with probabilities, not absolute
Genetic Screening
• Systematic testing of fetuses, newborn
children or individuals of any age to
determin potential genetic handicaps
Prenatal screening
A. Amniocentesis
1. Detect chromosomal abnormalities and other
disorders if coupled with biochemistry test
and/or rDNA techniques
2. Ultrasound locates fetus
3. Hyperdermic needle inserted into amnion to
withdraw 10-15 cm3 of amniotic fluid
4. Isolate and culture fetal cells, and subject
cells to a # of test
5. Usually administered between weeks 14-16
Genetically “normal”
• Our genotypes contain about 100,000 loci, 10%
of which may be polymorphic
• Parents of a child with a genetic disorder look
just like the rest of us, the combination of the
two just happens to bring together 2 rare
recessive alleles
• All of us are carriers (heterozygous) of several
genetic disease
• Risk of meeting and having children with
someone who has the same rare allele is minute
Human Genetic Diseases
What is inherited disease?
• Due to rare genotypes that produces
illadapted phenotypes in environments in
which more common genotypes give rise
to healthy phenotypes
• The majority of human genes, and
therefore the majority of genetic
disorders are carried on the autosomes
Mutations
• Mutations are changes in the genetic
material.
• There are 2 kinds of mutations
1. Chromosomal Mutations: involve
segments of chromosome, whole
chromosome, or entire sets of
chromosome
2. Gene Mutations: involve individual
genes
Chromosomal Mutations
• Usually so serious that carriers cant
reproduce
• Complex syndromes because it involves
many, many genes
• Detected using Karyotyping analysis
Karyotyping Analysis
1.Obtain cells by amniocentesis
2. Stimulate mitosis with
phytohemagglutinin
3. Arrest cells during metaphase using
colchicine
4. Stain and photograph under microscope
5. Cut up photo and arrange homologous
chromosomes
Two forms of chromosomal defects
1. Changes in number of chromosome
2. Structural abnormalities in chromosomes
Aneuploidy
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Changes in the number of chromosomes
The suffix used is -somy
Caused by an error in cell division
Trisomy: three copies of a chromosome
Monosomy: one member of a pair,
usually lethal
Aneuploidy autosomol
Disorders
(chromosomal number disorder)
1. Down Syndrome
• caused by the presence of an extra copy of
chromosome 21 (trisomy 21)
• It results in heart and circulatory problems,
a weakened immune system and mental
retardation.
• Some characteristics include a flattened
face, poor muscle tone, and short stature
• The degree of retardation varies greatly.
• 1/700 births, risk increases w/ age of parent
Aneuploidy of the sex
chromosomes
1. Turner’s Syndrome
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XO
1/3000 live births
20% of spontaneous abortions
Short female, deficient sexual
development
(YO is lethal probably b/c X carries genes
for clotting factor)
2. Klinefelter’s Syndrome
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XXY
1/500 males
Underdeveloped testes, infertile
Long legs, possible breast development,
high pitched voice
3. Triple X
• XXX
• Rare, usually normal
• Possible retardation and limited sexual
development
Structural abnormalities in
chromosomes
1. Translocation: chromosomes exchange
pieces
2. Inversion: reversal of a chromosome
segment
3. Deletion: loss of a chromosome
segment
4. Duplication: 2 copies of a segment
Autosomal Dominant Disorders
• Biochemical basis is poorly
understood
•Over 1700 traits
1. Huntingtons Chorea
• Produced by a single dominant allele located on
chromosome number 4.
• People who have this disease show no
symptoms until they are in there thirties or
forties, when the gradual damage to their
nervous system begins.
• They suffer a painful progressive loss of
muscle control and mental function until death
occurs.
• No known treatment
Autosomal Recessive Disorders
• Likely due to mutations which
produce alleles that encode defective
enzymes
•Over 1300 traits
1. Cystic Fibrosis
• the most common fatal disease in the US
amongst whites.
• Caused by a recessive allele on chromosome 7
• causes the lungs and breathing pathway to
become clogged due to interference with the
movement of chloride ions in and out of the
cell.
• Short life expectancy
2. Phenylketonuria (PKU)
• Absence of enzymes phenylalanine
hydroxylase causes increased levels of
phenylalanine in blood and tissue
• Causes mental retardation, epilepsy,
restlessness, and muscle stiffness
• Children tested at birth are put on diets
low in phenylalanine
3. Sickle Cell Anemia
• A blood disorder characterized by a sickled
shape blood cells.
• Caused by a point mutation where valine
replaces glutamic acid in hemoglobin
• In the US, this disorder is most common
among blacks.
• 100,000 deaths per year
4. Albinism
• Caused by a recessive allele on
chromosome 11.
• People with this disorder have no
pigment in their hair or skin
• Must avoid excessive exposure to bright
sunlight because they lack melanin
5. Tay-Sachs
• Fatal disorder
• most common amongst Medetar Jewish
communities.
• Children with Tay-Sachs suffer from
rapid breakdown of the nervous system
beginning at age 2 or 3.
Sex linked Disorders
250 traits, mostly recessive
1. Colorblindness
• recessive disorder in which a person
cannot distinguish between certain
colors.
• Most types of colorblindness are caused
by sex-linked genes located on the X
chromosome
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Hemophilia
recessive allele on the X chromosome.
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• In hemophilia, the protein antihemophilic factor
(AHF) necessary for normal blood clotting is
missing.
• Affects about 1/10,000 males and 1/100,000,000
females.
• People with hemophilia can bleed to death from
seemingly minor cuts and may suffer from internal
bleeding from bumps or bruises.
• It can be treated by injecting AHF into the patients.
3. Duchenne Muscular Dystrophy
• An inherited disease that results in the progressive
wasting away of skeletal muscle.
• Children with MD rarely live past early
adulthood.Wheelchair by age 10, death by age 20
• The most common form of MD is caused by a
defective version of the gene that codes for a
muscle protein known as dystrophin.
• This gene is located on the X chromosome
• 1/5000 live male births
• No cure