Ch 6, Part 1: Chr. MT's: Variation in #/arrangement (SEPT 29)

Part 1 How do chromosomes vary in number and what are the implications of aneuploidy?

How does variation in chromosome number happen?

what does not usually survive fertilization and what does that cause to be more rare

With non-disjunction, failure of chromosomes to migrate
properly during meiosis

Gametes missing a chromosome do not usually survive to fertilization, and so monosomy is much rarer than trisomy

How common is chromosome number variation?

How do dosage effects come into play

what is important in development

what organisms can tolerate variation more than the other

Dosage effects: haploinsufficiency occurs when not only
the presence but the quantity of a particular gene alters
fitness

-greatest effect for genes important in development
-organisms with simple development tolerate variation in chromosome number much better than those with complex development

Describe these terms for variation in chromosome number

-Euploid

-Aneuploid

-monosomy

-trisomy

Euploid: having the expected number of chromosomes

Aneuploid: having a different number of chromosomes than
expected; applies only to single chromosome sets
e.g. an additional copy of chromosome 21 is an example of
aneuploidy
-monosomy: having a single copy of a chromosome in a
diploid cell
-trisomy: having three copies of a chromosome in a
diploid cell

Describe these terms for variation in chromosome number

-Polyploid

-triploid

-tetraploid

Polyploid: having complete sets of chromosomes more than
expected
     -triploid: having three sets of chromosomes in a normally
diploid cell
     -tetraploid: having four sets of chromosomes in a normally
diploid cell

Does polyploidy occur in people

never

Does aneuploidy occur in people

-20% of pregnancies end in spontaneous abortion
-30% of these demonstrate aneuploidy, almost always
trisomy, for at least one chromosome
-6% of pregnancies result from syngamy between
aneuploid gametes

Humans tolerate aneuploidy at very few
chromosomes, which are they?

-X: Turner Syndrome, Klinefelter syndrome, etc.
-13 trisomy: Patau syndrome (largely lethal)
-18 trisomy: Edwards syndrome (largely lethal)
-21 trisomy: Down Syndrome

Describe Patau Syndrome

in which chromosome does it occur, how many?

how does penetrance and expressivity correlate

how many in live births

mortality rate

Trisomy of chromosome 13
-1 in 10,000-20,000 live births
-penetrance is complete, expressivity is variable
-80% don’t survive for one year even with intervention

what are the developmental abnormalities in Patau Syndrome

Cognitive and motor disability
Microcephaly
Vision defects
Polydactyly
Cyclopia
Omphalocele
Cleft palate
Genital defects
Kidney defects
Heart defects

Describe Edwards Syndrome

in which chromosome does it occur, how many?

how does penetrance and expressivity correlate

how many in live births

mortality rate

Trisomy of chromosome 18
-1 in 1,000 live births
-penetrance is complete, expressivity is variable
-92% don’t survive for one year even with intervention

what are the developmental abnormalities in Edwards Syndrome

Cognitive and motor disability
Microcephaly
Hydrocephaly
Arthrogyropsis
Esophageal atresia

Describe Down Syndrome

in which chromosome does it occur, how many?

how does penetrance and expressivity correlate

how many in live births

Trisomy of chromosome 21
-1 in 800 live births
-Life expectancy 50-60 years
-penetrance is complete, expressivity is variable

what are the developmental abnormalities in Down Syndrome

Cognitive disability
Psychomotor disability
Heart defects
Bone shortening
Low muscle tone
Epicanthic fold
Protruding tongue
High incidence of leukemia

in down syndrome…

What increases in frequency

what decreases in incidence and why

Increases in frequency with the age of the mother, cause unknown

Decrease in the incidence of solid tumor formation
-over-expression of vascular endothelial growth factor
prevents vascularization of tumors