Transcript Down syndrome is caused by trisomy 21

Types of Chromosome Mutations
Chromosome Mutations
Deletion/
Deficiency
Duplication
Inversion
A B C
D E F
A C
D E F
A B C
D E F
A B B C
A B C
D E F
A E D
C B F
A B C
D E F
A B C
D J K
G H
J K
G H
E F
D E F
Translocation
I
I
Reciprocal Translocation
Reciprocal translocation
heterozygotes are
semisterile.
50% of gametes are
genetically unbalanced.
In plants, these gametes
are not viable.
In animals, zygotes that
are formed by these
gametes are not viable.
Adjacent segregation
produces genetically
unbalanced gametes.
Alternate segregation
produces genetically
balanced gametes.
Down Syndrome and Translocation Heterozygote
• Down syndrome is caused by trisomy 21 (3 copies of
chromosome 21).
• 95% of Down syndrome cases are associated with
nondisjunction and shows no familial recurrence.
• The other 5% (familial Down syndrome) is attributed
to Robertsonian translocation between chromosome
21 and chromosome 14.
Chromatin and Gene Expression
Heterochromatin
•
Contains methylated histones (H3)
•
Associated with heterochromatin protein-1 (HP-1)
Transcriptionally Active Euchromatin
•
Contains hyperacetylated histones
Prevention of Heterochromatin Formation
•
DNA elements (barrier insulators) promote binding of
histone acteyltransferase
Gene Silencing is Caused by the Spread of Heterochromatin
When a chromosome mutation places a gene next to
heterochromatin, the gene can become inactivated.
Inversion, deletion, duplication, and translocation
can place a gene next to heterochromatin.
Heterochromatin May Spread Farther in Some Cells Than in Others
Position-effect Variegation
A heterozygote for a gene and a
translocation can show variegated
phenotype for that gene.
Position-effect variegation is exhibited
by this w+/w heterozygote.
Wild-type allele is no longer wild-type
in its expression in some of the eye
facets.
Any chromosomal change that places
a locus next to heterochromatin can
result in inactivation of that gene.
A tissue or organ that is comprised of
a mixture of cells that express one or
the other phenotype exhibit this
variegation.
Types of Chromosome Mutations
The fates of a million implanted
human zygotes
50% of spontaneous
abortions are
associated with
chromosome
abnormalities.
Over half of these
are trisomics, with
trisomy 21
accounting for 9% of
them.
18% of
abnormalities are
the Turner condition.
~ 0.6% of birthed infants have
chromosome abnormalities.
~ 36% of birthed infants with
chromosome abnormalities are
aneuploidy of sex chromosome.
~ 23% of birthed infants with
chromosome abnormalities are trisomics.
Molecular Basis for
Relationship between Genotype and Phenotype
genotype
DNA
DNA sequence
transcription
RNA
translation
protein
function
phenotype
organism
amino acid
sequence