Classic%20Methods%20of%20Genetic%20Analysis

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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

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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

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Genetic Screening

• Systematic testing of fetuses, newborn children
  or individuals of any age to determin potential
  genetic handicaps

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Prenatal screening

• Amniocentesis
• Detect chromosomal abnormalities and other
  disorders if coupled with biochemistry test
  and/or rDNA techniques
• Ultrasound locates fetus
• Hyperdermic needle inserted into amnion to
  withdraw 10-15 cm3 of amniotic fluid
• Isolate and culture fetal cells, and subject
  cells to a of test
• Usually administered between weeks 14-16

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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

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Human Genetic Diseases
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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

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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

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Chromosomal Mutations

• Usually so serious that carriers cant reproduce
• Complex syndromes because it involves many, many
  genes
• Detected using Karyotyping analysis

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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

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Two forms of chromosomal defects

1. Changes in number of chromosome
2. Structural abnormalities in chromosomes

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Aneuploidy

• 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

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Aneuploidy autosomol Disorders(chromosomal
number disorder)
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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

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Aneuploidy of the sex chromosomes
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1. Turners Syndrome

• 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)

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2. Klinefelters Syndrome

• XXY
• 1/500 males
• Underdeveloped testes, infertile
• Long legs, possible breast development, high
  pitched voice

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3. Triple X

• XXX
• Rare, usually normal
• Possible retardation and limited sexual
  development

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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

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Autosomal Dominant Disorders

• Biochemical basis is poorly understood
• Over 1700 traits

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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

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Autosomal Recessive Disorders

• Likely due to mutations which produce alleles
  that encode defective enzymes
• Over 1300 traits

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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

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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

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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

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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

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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.

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Sex linked Disorders

• 250 traits, mostly recessive

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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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2. Hemophilia

• recessive allele on the X chromosome.
• 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.

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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