Download The Human Genome

The Human Genome
Chapter 15
Studying Human Genetics
• Difficulties:
– Controlled matings not feasible
– Small size of families
– Long generation time
• The Human Genome:
– The total genetic information in human cells
– Includes the DNA from the nucleus and mitochondria
– We know the sequence, but not which parts code for proteins
and which are non-coding segments
• We also use:
– Karyotyping
– Pedigrees
Karyotypes
• Cell sample is taken from actively dividing cells (blood,
skin, fetal cells)
• Cells are cultured and division is stopped during
metaphase when chromosomes are visible
• Cells are placed in a hypotonic solution to cause
swelling and spreading of chromosomes
• Photomicrograph is made and scanned, homologous
chromosomes are matched and arranged in numbered
pairs from longest to smallest (except pair #21)
• Deviations in chromosome number or structure can be
detected
• Mutations at the gene level cannot be examined with
this method
Making a karyotype
Pedigrees
• Each row represents a separate generation &
labeled with a Roman numeral
• Earliest generation at the top; most recent at
the bottom
• Individuals are numbered left to right in each
generation
• Horizontal lines connect parents; vertical line
drops from parents to offspring; offspring are
placed from left to right – oldest to youngest
• Males are squares, females are circles;
individuals with the trait are filled in;
heterozygous carriers are filled in halfway
Pedigrees
Autosomal dominant
Autosomal recessive
The Human Genome Project
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The entire sequence of human DNA
Completed in 2003
An estimated 30,000 genes
Only 1% - 3% of our DNA codes for
protein
• The other is either introns, regulatory
DNA, or has some as yet unknown
function
The Human Genome Project:
A Timeline
Human Genome Project:
The Future
• Sequencing other species – finding our
similarities and differences may lead to
increased understanding
• Bioinformatics – all the data is stored in a
data base for comparison; may allow for
identification of gene, gene function, and
evolutionary relationships
• Pharmacogenetics – customizes drugs to
match a patient’s genetic makeup in order to
reduce chances of side effects
• Proteomics – the study of the proteins
produced by the individual cell
Chromosome Abnormalities
• Aneuploidy – incorrect chromosome
number
– Disomy – normal; 2 of each kind
– trisomy – abnormal; 3 of one kind
– Monosomy – abnormal; missing 1 of a pair
• Result from nondisjunction during
meiosis – a homologous pair of
chromosomes fail to separate
Aneuploidies
• Down Syndrome:
• Trisomy 21
• Abnormal physical and mental
development; wide range of expression
• 1 out of every 800 live births; incidence
increases with increasing maternal age
Sex Chromosome Aneuploidies
• Klinefelter syndrome: XXY
– male; small testes, sterile, unusually tall, some with
breast development, some with mild mental
retardation
• Turner syndrome: X0 (0 = missing)
– female; small reproductive organs, sterile
• XYY karyotype
– male; fertile; increased aggression????
Abnormal chromosome structure
• Translocation: chromosome fragment breaks off and
attaches to a nonhomologous chromosome
– Translocation Down syndrome – involves
chromosome 21 and 14
• Deletion: part of a chromosome is missing
– Cri du chat – part of chromosome 5
• Fragile site: place where the chromatid appears
attached by only a thin thread of DNA
– Fragile X syndrome – the most common form of
inherited mental retardation; impacts males more
than females
Single-gene mutations
• PKU: affects amino
acid metabolism
– Autosomal recessive
– 1 in 10,000 live births
– Cannot convert
phenylalanine in the diet
– This compound
accumulates in the body
and damages the central
nervous system
– Can cause severe mental
retardation
All U.S. born infants are
tested and victims placed on
a low phenylalanine diet,
thereby allowing them to
develop normally
Single-gene mutations…
• Sickle cell anemia:
abnormal hemoglobin
formation
– Autosomal recessive
– 1 in 500 African American
births
– Misshapen cells slows
blood flow and can even
block small veins, causing
organ damage, pain, and
anemia
– Heterozygous individuals
for sickle cell trait are
more resistant to malaria
Red blood cells are
sickle shaped after
oxygen has been
released
Single-gene mutations…
• Cystic fibrosis:
abnormal secretions
– Autosomal recessive
– 1 in 2500 births
– Respiratory system
gets clogged with
thick mucus
– Also can cause
digestive issues
Single-gene mutations…
• Tay-Sachs disease:
absence of an
enzyme needed for
proper brain
chemistry
– Autosomal recessive
– 1 in 4,000 U.S. Jews
– Blindness, severe
mental retardation,
death before the age
of 5
Single-gene mutations…
• Huntington’s
Disease: mutated
brain protein
– Autosomal dominant
– 1 in 20,000 U.S.
births
– Symptoms begin in a
person’s 30s or 40s –
after they have had
their children
Single-gene mutations…
• Hemophilia A:
improper formation of
blood clotting factors
– X-linked recessive
– Affected individuals
almost always male
Gene Therapy
• Most genetic diseases have treatments
but not cures… why?
• Gene therapy tries to replace the
defective gene with a normal one in the
appropriate cells, often by using viral
vectors
• There are both technical and ethical
problems associated with this
Genetic testing and counseling
• Genetic counseling: before pregnancy
– Pedigree and/or karyotype analysis
• Prenatal testing: before birth
– Ultrasound imaging
– Amniocentesis
– Chorionic villus sampling
• Genetic screening: after birth
– Blood tests
– Karyotypes
Ethical considerations
• Consanguineous matings
• Genetic discrimination
• Eugenics