ANEUPLOIDY
• Having too many or too few chromosomes
compared to a normal genotype
• Aneuploid organisms have unbalanced sets
of chromosomes due to an excess or
deficiency of individual chromosomes
• This creates an imbalance among the genes
and causes an abnormal phenotype or even
death
ANEUPLOIDY
• Most autosomal aneuploids are incompatible
with life
• Autosomal nondisjunction occurs at a
reasonable high frequency in humans but the
zygote does not develop
• Aborts spontaneously soon after conception
• Humans do not tolerate aneuploidy well,
especially monosomies
• Excess of chromosomes is tolerated better
than a deficiency so trisomies are more
viable than monosomies
TRISOMY 3 COPIES OF A SINGLE CHROMOSOME
• A few types of trisomic zygotes are capable
of survival
• Trisomy 21
• Trisomy 18
• Trisomy 13
• Only those trisomies involving the smallest
or heterochromatic chromosomes are able to
survive at all
CHROMOSOME 21
• Chromosome 21 has been described as
a desert harboring a million base pair
stretch with only 225 genes
• Chromosome 22 is a gene jungle with
545 genes
DOWN SYNDROME TRISOMY 21
• 1866, Dr. John Langdon Down noticed that
about 10% of the residents at his asylum
resembled each other and could be easily
distinguished from the rest of his patients
• Took geneticists another 90 years to
determine the correct human chromosome
number and it was not until 1959 that it was
known that individuals with Down Syndrome
have 3 copies of the smallest chromosome
DOWN SYNDROME TRISOMY 21
• Most common and best known genetic
disorder
• Accounts for about 10% of all mentally
disabled children
• Occurs in about 1/750 live births in all ethnic
groups
• Accounts for about 10% of all mentally
disabled children
• Nearly all cases occur just once within a
given family
• Only about 2-5% of cases run in families
DOWN SYNDROME TRISOMY 21
• Babies with this disorder grow slowly and
have poor muscle tone
• Lack of muscle tone gives them a floppy
appearance
• Individuals are generally shorter than
average
• All parts of their bodies are shortened due to
poor skeletal development, including the
hands and fingers
DOWN SYNDROME TRISOMY 21
• Affected individuals have
Š Sparse hair
Š a protruding tongue and thick lips
• Their hands have an irregular pattern of
creases
• Their joints are loose and they have
poor reflexes
• Motor development is delayed
DOWN SYNDROME TRISOMY 21
• 1/2 of the children born with Down
syndrome are born with severe heart
malformations
• 15% of the babies die in their first year
from heart abnormalities
• Many others die before the age of 5
• Those who do live beyond the fifth year
of life have an average life expectancy
of 50 years
DOWN SYNDROME TRISOMY 21
• Leukemia is 15-20 times more prevalent
in people with Down syndrome than in
the general population
• Adult males have poorly developed
genitals and are sterile
• Adult females can have children
• 1/2 of their children are born with Down
syndrome
DOWN SYNDROME TRISOMY 21
• Maturation is delayed but following puberty
there is a rapid onset of aging
• Those over age 40 develop the black fibers of
amyliod proteins in their brains
• These proteins are associated with
Alzheimers
• The chance of a person with Trisomy 21
developing Alzheimer’s disease is 25%
compared to 6% in the general population
TRISOMY 21
• Karyotyping has shown that not all of
chromosome 21 has to be present in
triplicate to produce Down syndrome
• In a few rare individuals, the only extra
chromosomal material is the distal half of the
long arm of chromosome 21.
• This region houses most of the genes
including a gene for an enzyme involved in
aging and a leukemia causing gene
ABNORMAL CHROMOSOME STRUCTURE
• Structural chromosomal defects
include missing, extra, or inverted
genetic material within a chromosome
or exchanged parts of a chromosome
TRANSLOCATION
• In translocations, nonhomologous
chromosomes exchange parts
• 2 types
Š Robertsonian translocation
Š Reciprocal translocation
ROBERTSONIAN TRANSLOCATION
Robertsonian translocation the short arms
of 2 different acrocentric chromosomes
break, leaving sticky ends that then cause
the 2 long arms to adhere
Š A new large chromosome forms from the
long arms of the two different
chromosomes
Š This individual may produce unbalanced
gametes
Fig. 12.17
ROBERTSONIAN TRANSLOCATION
• A carrier parent with 45 chromosomes one of
which is the combined 14q21q, will produce
3 kinds of offspring
Š Phenotypically and karyotypically normal
Š Phenotypically unaffected translocation
heterozygote
Š Translocation Down syndrome individual
• The risk of a carrier having a child with Down
syndrome is 15%
• The condition is not related to age
MATERNAL EFFECT
• 1930 a maternal age effect was shown to be
a factor in most cases, not the number of
children in a family
• Frequency of Down syndrome births
increases with advancing maternal age
• Women over 35 years of age produced about
25% of all the babies born with Down
syndrome
FEMALE MEIOSIS
• The effect may be a consequence of the long delay
between prophase I and the first meiotic division in
human oocytes
• Human oocytes begin meiosis before the female is
born
• They remain in a state of suspended animation until
the girl hits puberty some 10 -13 years later
• Egg ovulated by a 45 year old female has
been in suspended animation for 45 years
• Plenty of time for something to go wrong
TRISOMY
• Trisomy 18 Edward Syndrome
Š 1/6000 live births
• Trisomy 13 Patau Syndrome
Š 1/12,000 live births
• Both lead to early death by 2.5 months
• Nearly all cases die during the first year of
life
• All suffer from profound mental retardation.