Download Karyotypes

Karyotypes & Human genetics
SBI 3U
Biology
Nondisjunction
• occurs when either homologous chromosomes
fail to separate during anaphase I of meiosis, or
sister chromatids fail to separate during
anaphase II. The result is that one gamete has 2
copies of one chromosome and the other has no
copy of that chromosome. (The other
chromosomes are distributed normally.)
• If either of these gametes unites with another
during fertilization, the result is aneuploidy
(abnormal chromosome number)
• A trisomic cell has one extra chromosome (2n
+1) = example: trisomy 21. (Polyploidy refers to
the condition of having three homologous
chromosomes rather then two)
• A monosomic cell has one missing
chromosome (2n - 1) = usually lethal except for
one known in humans: Turner's syndrome
(monosomy XO).
• The frequency of nondisjunction is quite high in
humans, but the results are usually so
devastating to the growing zygote that
miscarriage occurs very early in the pregnancy.
• If the individual survives, he or she usually has a
set of symptoms - a syndrome - caused by the
abnormal dose of each gene product from that
chromosome.
Patau syndrome (trisomy 13):
• serious eye, brain,
circulatory defects as
well as cleft palate.
1:5000 live births.
Children rarely live
more than a few
months.
Edward's syndrome (trisomy 18):
• almost every organ
system affected
1:10,000 live births.
Children rarely live
more than a few
months.
47, XYY males
• Individuals are somewhat
taller than average and
have below normal
intelligence. At one time
(~1970s), it was thought
that these men were
likely to be criminally
aggressive, but this
hypothesis has been
disproven over time.
Trisomy X: 47, XXX
• females. 1:1000 live
births - healthy and
fertile - cannot be
distinguished from
normal female except
by karyotype
These children have severe mental retardation, a small
head with unusual facial features, and a cry that sounds like
a distressed cat.
Non-disjunction – trisomy 21
• In humans, nondisjunction is most often
associated with the 21st chromosome,
producing a disease known as Down's
syndrome (also referred to as trisomy 21).
Sufferers of Down's syndrome suffer mild to
severe mental retardation, short stocky body
type, large tongue leading to speech difficulties,
and (in those who survive into middle-age), a
propensity to develop Alzheimer's Disease.
Ninety-five percent of Down's cases result from
nondisjunction of chromosome 21.
• The incidence of Down's Syndrome
increases with age of the mother, although
25% of the cases result from an extra
chromosome from the father.
Sex-chromosome abnormalities may also be caused by
nondisjunction of one or more sex chromosomes. Any
combination (up to XXXXY) produces maleness. Males with more
than one X are usually underdeveloped and sterile. XXX and XO
women are known, although in most cases they are sterile.
Sex-linked Traits
• Color blindness afflicts 8% of males and
0.04 % of human females. Color
perception depends on three genes, each
producing chemicals sensitive to different
parts of the visible light spectrum. Red and
green detecting genes are on the Xchromosome, while the blue detection is
on an autosome.
Sex-linked disorders in humans
• Sex chromosomes
not only determine
sex, they also have
genes for many
functions.
Hemophilia
• A group of diseases in which blood does
not clot normally. Factors in blood are
involved in clotting. Hemophiliacs lacking
the normal Factor VIII are said to have
Hemophilia A, the most common form.
Normal Factor VIII can be supplied at a
high dollar and health risk cost, although
the development of biotechnologically
engineered Factor VIII produced by
bacteria lessens the health risk.
Hemophilia – the royal disease
• England's Queen Victoria was a carrier for
this disease. The allele was passed to two
of her daughters and one son. Since royal
families in Europe commonly intermarried,
the allele spread, and may have
contributed to the downfall of the Russian
monarchy (Czar Nicholas' son Alexei
suffered from hemophilia A inherited from
his mother who carried Victoria's genetic
secret).
Muscular Dystrophy
• Muscular dystrophy is a term encompassing a variety of
muscle wasting diseases. The most common type,
Duchenne Muscular Dystrophy (DMD), affects cardiac
and skeletal muscle, as well as some mental functions.
DMD is an X-linked recessive occurring in 1 in 3500
newborns. Most sufferers die before their 20th birthday.
In 1987, Louis Kunkel claimed to have isolated a protein,
dystrophin, present in normal individuals (about 0.002 %
of their muscle protein) but absent in two individuals with
DMD. The lack of dystrophin is accompanied with a
condition of muscle hardening known as fibrosis, which
restricts blood supply to the muscle which then die.
Genetically Inherited Human
Disorders:
• Autosomal recessive disorders: Show
up only in the homozygous recessive
person (aa) who inherits a recessive allele
from both parents, who were carriers
• (Aa x Aa).
• (25% chance of this happening)
Cystic Fibrosis:
• Homozygous recessives (cc) have cystic
fibrosis - body cannot make needed
chloride channel, high concentrations of
extracellular chloride causes mucous to
build up, infections, pneumonia. Diet,
antibiotics and treatment can extend life to
25 years or more.
Tay-Sachs:
• Enzyme that breaks down brain lipids is
non-functional in homozygous recessives
(tt). Buildup of lipids causes death by age
2-3.
Sickle-cell disease:
• The most common
inherited disease of
African-Americans (1:400
affected). Homozygous
recessives (ss) make
abnormal form of
hemoglobin that deforms
red blood cells and
causes a cascade of
symptoms (clogging of
blood vessels, organ
damage, kidney failure).
Advantages of Mutations
• For some disease alleles, being a heterozygote
offers protection against another disease.
Examples:
• Sickle cell disease: Ss carriers are resistant to
malaria (note: 1:10, or 10% African-Americans
are carriers Ss)
• Cystic fibrosis: Cc carriers are resistant to
cholera (note: 1:25, or 4% of caucasians is a
carrier Aa).
• Tay-Sachs: Tt carriers are thought to be more
resistant to tuberculosis
Autosomal dominant disorders
• Child will show the phenotype if he / she
receives just 1 allele from either parent.
With just 1 parent affected, 50% chance of
offspring being affected.
Achondroplasia
• (dwarfism): AA =
Homozygous
dominant is lethal fatal (spontaneous
abortion of fetus). Aa
= dwarfism. aa = no
dwarfism. 99.96% of
all people in the world
are homozygous
recessive (aa).
Polydactyly
• (extra fingers or
toes): PP or Pp =
extra digits, aa = 5
digits. 98% of all
people in the world
are homozygous
recessive (pp).
Progeria
(very premature aging):
Spontaneous mutation of one
gene creates a dominant
mutation that rapidly
accelerates aging
Huntington's chorea
• Is also a lethal
dominant condition
(HH = fatal) but
homozygous
dominant (Hh) people
live to be ~40 or so,
then their nervous
system starts to
degenerate. Woody
Guthrie died of
Huntington's.
Woody Guthrie
The genetic locus for Huntington's has been pinpointed to
the tip of chromosome 4 - there is now a test for
Huntington's - if you were from a Huntington's family, would
you want to know?
The HD gene is located on the short (p) arm of
chromosome 4 at position 16.3.
The HD gene provides instructions for making a protein
called huntingtin. Although the exact function of this protein
is unknown, it appears to play an important role in nerve
cells and is essential for normal development before birth.
Duplication:
• If the fragment joins the homologous
chromosome, then that region is repeated
• Example - Fragile X: the most common form of
mental retardation. The X chromosome of some
people is unusually fragile at one tip - seen
"hanging by a thread" under a microscope. Most
people have 29 "repeats" at this end of their Xchromosome, those with Fragile X have over
700 repeats due to duplications. Affects 1:1500
males, 1:2500 females.
Inversion:
• a fragment can be broken and rejoined in the
reverse orientation, reversing the fragment
within a chromosome.