Download Aim: What are some gene and chromosome mutations

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Do Now: List 5 facts you know about people
with Down’s Syndrome.
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1) Down’s syndrome is a rare genetic disease.
Fact: 1 in 691 births result in Down’s
Syndrome (6000/year)
2) Most children with Down syndrome are
born to older parents.
Fact: Most children (80%) with Down
Syndrome are born to women younger than
35 years old simply because younger women
have more children. However, the incidence
of births of children with Down syndrome
increases with the age of the women.
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3) Children with Down syndrome must be placed in
segregated special education programs.
Fact: Children with Down syndrome have been
included in regular academic classrooms in schools
across the country. The current trend in education
is for full inclusion in the social and educational life
of the community. Increasingly, individuals with
Down Syndrome graduate from high school with
regular diplomas, participate in post-secondary
academic and college experiences and in some
cases receive college degrees.
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4) Adults with Down syndrome are
unemployable.
Fact: They are being employed in small and
medium-sized offices by banks, corporations,
nursing homes, hotels and restaurants. They
work in clerical positions, childcare, the
sports field, entertainment, and the computer
industry. They bring enthusiasm, reliability
and dedication to their jobs.
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5) Adults with Down syndrome are uable to
form close interpersonal relationships:
Fact: People with Down syndrome date,
socialize, and marry.
6) Down syndrome can never be cured:
Fact: Researchers are making great strides in
identifying the genes on chromosome 21 that
cause the phenotypic characteristics
associated with the syndrome. They are
optimistic that they will be able to correct or
prevent these symptoms.
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Nondisjunction occurs when problems with
the meiotic spindle cause errors in daughter
cells.
◦ 1)tetrad chromosomes
do not separate
properly during
meiosis I.
◦ 2) sister chromatids may fail
to separate during
meiosis II.
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Gamete + nondisjunction gamete =
aneuploidy.
◦ Trisomic cells have three copies of a particular
chromosome type and have 2n + 1 total
chromosomes.
◦ Monosomic cells have only one copy of a particular
chromosome type and have 2n - 1 chromosomes.
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One aneuploid condition, Down syndrome, is
due to three copies of chromosome 21.
◦ It affects one in 700 children born in the United
States.
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Klinefelter’s syndrome, an XXY male, occurs once in
every 2000 live births.
◦ These individuals have male sex organs, but are sterile.
◦ There may be feminine characteristics, but their intelligence
is normal.
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Males with an extra Y chromosome (XYY) tend to
somewhat taller than average.
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Trisomy X (XXX), which occurs once in every 2000 live
births, produces healthy females.
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Monosomy X or Turner’s syndrome (X0), which occurs
once in every 5000 births, produces phenotypic, but
immature females.
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Tests are also available to determine in utero
if a child has a particular disorder.
One technique, amniocentesis, can be used
beginning at the 14th to 16th week of
pregnancy to assess the presence of a
specific disease.
◦ Fetal cells extracted from amniotic fluid are
cultured and karyotyped to identify some disorders.
◦ Other disorders can be identified from chemicals in
the amniotic fluids.
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A second technique, chorionic villus sampling
(CVS) can allow faster karyotyping and can be
performed as early as the eighth to tenth
week of pregnancy.
◦ This technique extracts a sample of fetal tissue
from the chrionic villi of the placenta.
◦ This technique is not suitable for tests requiring
amniotic fluid.
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Organisms with more than two complete sets
of chromosomes, have undergone polypoidy.
Triploid = normal set + nondisjunction set
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Polyploidy is relatively common among plants
and much less common among animals.
Polyploids are more nearly normal in
phenotype than aneuploids.
One extra or missing chromosome apparently
upsets the genetic balance during
development more than does an entire extra
set of chromosomes.
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Breakage of a chromosome can lead to four
types of changes in chromosome structure.
A deletion occurs when a chromosome
fragment lacking a centromere is lost during
cell division.
◦ This chromosome will be missing certain genes.
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A duplication occurs when a fragment
becomes attached as an extra segment to a
sister chromatid.
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Deletions, even in a heterozygous state,
cause severe physical and mental problems.
One syndrome, cri du chat, results from a
specific deletion in chromosome 5.
◦ These individuals are mentally retarded, have a
small head with unusual facial features, and a cry
like the mewing of a distressed cat.
◦ This syndrome is fatal in infancy or early childhood.
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An inversion occurs when a chromosomal
fragment reattaches to the original
chromosome but in the reverse orientation.
In translocation, a chromosomal fragment
joins a nonhomologous chromosome.
◦ Some translocations are reciprocal, others are not.
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Cystic fibrosis (strikes one of every 2,500 whites of European
descent.)
◦ One in 25 whites is a carrier.
◦ The normal allele codes for a membrane protein that
transports Cl- between cells and the environment.
◦ If these channels are defective or absent, there are
abnormally high extracellular levels of chloride that causes
the mucus coats of certain cells to become thicker and
stickier than normal.
◦ This mucus build-up in the pancreas, lungs, digestive tract,
and elsewhere favors bacterial infections.
◦ Without treatment, affected children die before five, but
with treatment can live past their late 20’s.
Chloride channel
normal lungs
airway
Cl–
transports salt through protein
channel out of cell
Osmosis: H2O follows Cl–
Cl– channel
H 2O
cells lining
lungs
cystic fibrosis
Cl–
H 2O
bacteria & mucus build up
thickened mucus
hard to secrete
mucus secreting glands
delta F508
loss of one
amino acid
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Primarily Jews of eastern European (Ashkenazi)
descent & Cajuns (Louisiana)
◦ strikes 1 in 3600 births
 100 times greater than incidence among
non-Jews
◦ non-functional enzyme fails to breakdown lipids
in brain cells
 fats collect in cells destroying their function
 symptoms begin few months
after birth
 seizures, blindness &
degeneration of muscle &
mental performance
 child usually dies before 5yo
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The most common inherited
disease among blacks is
sickle-cell disease.
◦ It affects one of 400 African
Americans.
◦ It is caused by the substitution
of a single amino acid in
hemoglobin.
◦ When oxygen levels in the blood
of an affected individual are
low, sickle-cell hemoglobin
crystallizes into long rods.
◦ This deforms red blood cells
into a sickle shape.
PLEIOTROPHIC
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pleiotrophic (single gene has many phenotypic
effects) such as:
◦ 1) breakdown of red blood cells leading to anemia, fatigue,
and heart failure
◦ 2) clumping and clogging of small blood vessels leading to
brain damage and more frequent infections
◦ 3) accumulation of sickle cells in spleen
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Substitution of one amino acid in polypeptide
chain
hydrophilic
amino acid
hydrophobic
amino acid
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2 alleles are codominant
◦ both normal & mutant hemoglobins are
synthesized in heterozygote (Aa)
◦ 50% cells sickle; 50% cells normal
◦ carriers usually healthy
◦ sickle-cell disease
triggered under blood
oxygen stress
 exercise
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Malaria
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In tropical Africa, where malaria is common:
◦ single-celled eukaryote parasite spends part of its
life cycle in red blood cells
◦ homozygous dominant individuals die of malaria
◦ homozygous recessive individuals die of sickle cell
anemia
◦ heterozygote carriers are relatively free of both
 reproductive advantage
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High frequency of sickle
cell allele in African
Americans is vestige of
African roots
Prevalence of Malaria
Prevalence of Sickle
Cell Anemia
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A lethal dominant allele can escape
elimination if it causes death at a relatively
advanced age, after the individual has already
passed on the lethal allele to his or her
children.
One example is Huntington’s disease, a
degenerative disease of the nervous system.
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Dominant inheritance
◦ repeated mutation on end of
chromosome 4
 mutation = CAG repeats
 glutamine amino acid repeats in protein
 one of 1st genes to be identified
1872
◦ build up of “huntingtin” protein in brain causing
cell death
 memory loss
 muscle tremors, jerky movements
 “chorea”
 starts at age 30-50
 early death
 10-20 years after start
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Some genetic tests can be detected at birth by
simple tests that are now routinely performed in
hospitals.
One test can detect the presence of a recessively
inherited disorder, phenyketonuria (PKU).
◦ This disorder occurs in one in 10,000 to 15,000 births.
◦ Individuals with this disorder accumulate the amino acid
phenylalanine and its derivative phenypyruvate in the
blood to toxic levels.
◦ This leads to mental retardation.
◦ If the disorder is detected, a special diet low in
phenyalalanine usually promotes normal development