1. DOWN SYNDROME

2. non-disjunction
- the failure of homologs or sister chromatids to separate properly
to opposite poles during meiosis or mitosis
aneuploidy
- a chromosome number that differs from normal (does not include situations where entire sets of chromosomes are lost or duplicated)
trisomy
- an aneuploidy with an extra chromosome of one type, producing
a chromosome number of 2N+1
monosomy
- an aneuploidy in which one member of a chromosome pair is
missing, producing a chromosome number of 2N-1

3. DOWN SYNDROME PHENOTYPE
Epicanthic fold in eye corner
IQ seldom above 70
Life expectancy short, few survive to 50
Have simian crease
May have heart defects
May have small heads
May have furrowed tongues
20 fold increased risk of leukemia

4. GENERAL INFORMATION
Down caused by non-disjunction of chromosome 21, correlated with age of mother and onset of menopause.
Down also caused by attaching chromosome 21 to 14 (translocation), referred to as familial Downs.
Amniocentesis and chorionic villi sampling developed because of defects such as Down. Newer, not yet perfected technology, samples fetal cells from maternal circulation. Once fully developed this method will be safer because it is not invasive.
Extra copies of human chromosomes generally not well tolerated. Chromosome 21 has only 225 functional genes.
Trisomy for chromosomes with more genes results in more pronounced defects; e.g. trisomy for chromosome 16 is common but lethal.

5. AI AII Primary non-disjunction 21/21 21/21 75% of Down occur at MI
90% of all chromosome
abnormalities are MI / maternal AI
AII
21/ /21

6. Note: non-disjunction very unlikely to occur twice in same meiosis
2nd non-disjunction
21/21 21
Note:
non-disjunction
very unlikely to
occur twice in
same meiosis

7. Mother’s gametes
21/
Father’s gametes 21
Offspring: /21/ / /21
Down Lethal Normal
2N: 46+1 = N: 46-1 = N: 46
(2N+1 = 47) (2N-1 = 45)

8. Karyotype of Down Syndrome Individual
extra chromosome
21 comes from
mother 95% of time
other viable
individuals with extra
chromosome are Patau
(chromosome 13) and
Edwards Syndrome
(chromosome 18)
…both die 3-4 months
chromosomes 13, 18,
and 21 have the
fewest genes
individuals missing one chromosome
almost never seen and never viable;
may unmask recessive lethal or haploinsufficient genes

9. Correlation Down Syndrome and Maternal Age
probability of
Down related to
onset of
menopause,
aberrant hormone
levels may affect
oocyte maturation

10. Familial Down Syndrome
long arms of chromosomes
14 and 21 fused with one
common centromere
(Robertsonian translocation)
acentric fragments lost….
apparently without serious
consequence for individual
genes lost are primarily rRNA
(encode RNA found in
ribosomes)…..additional copies
located elsewhere in genome
fused centromere has
chromosome 14 identity at
meiosis

11. Offspring from Mating Between Translocation Carrier and Normal Individual
1/3 of surviving
offspring expected
to be Down
another 1/3 surviving
progeny expected to
be carriers