nucleosome and chromosome disorders bty 107
DESCRIPTION
very cruicial for msc and bsc begineers.TRANSCRIPT
Chromatin is a complex of macromolecules
found in cells, consisting of DNA, protein and
RNA.The primary functions of chromatin are 1) to
package DNA into a smaller volume to fit in the
cell, 2) to reinforce the DNA macromolecule to
allow mitosis, 3) to prevent DNA damage,
and 4) to control gene expression and DNA
replication.
Forms of Chromatin:
Euchromatin is a lightly packed form of
chromatin (DNA, RNA and protein)
Euchromatin comprises the most active portion
of the genome within the cell nucleus. 92% of the
human genome is euchromatic.
Heterochromatin is a tightly packed form of DNA, which comes in multiple
varieties.
Histones: Basic proteins. Play a major role in chromatin. They are present in the
chromatin of all eukaryotes in amounts equivalent to the amounts of DNA .
The major five histones are known as H1, H2A,H2B,H3 and H4. The molar ratio of
histones are 1H1, 2HA,2HB,2H3 and 2H4.
Composition of Histones
In eukaryotes, the DNA-protein complex, called chromatin is ordered into
higher structural levels than the DNA-protein complex in prokaryotes
Eukaryotic DNA
Is precisely combined with a large amount of
protein
Eukaryotic chromosomes
Contain an enormous amount of DNA
relative to their condensed length
Proteins called histones are responsible for the first level of DNA packing in
chromatin and bind tightly to DNA
The association of DNA and histones seems to remain intact throughout the cell
cycle
Nucleosomes: The histones specifically complexed with DNA to produce the basic structural
subunits of chromatin, small(approx. 110 Ao in diameter) ellipsoidal “beads”called nucleosomes.
Solenoid: The nucleosomes, and the DNA strands linking them, are packed closely together to
produce a 30nm diameter helix with about six nucleosome per turn. This is known as the 30nm
fibre, or the solenoid fibre.
It has a packing ratio of about 440, that 40um of DNA are packed into 1um length of
solenoid.
In electron micrographs
Unfolded chromatin has the appearance of beads on a string
Each “bead” is a nucleosome: The basic unit of DNA packing
Nucleosomes (10-nm fiber)
The next level of packing forms the 30-nm chromatin fiber
Nucleosome
30 nm
30-nm fiber
The 30-nm fiber, in turn forms looped domains, making up a 300-nm fiber
Protein scaffold
300 nm
Looped domains (300-nm fiber)
Loops
Scaffold
In a mitotic chromosome the looped domains themselves coil and fold forming
the characteristic metaphase chromosome
700 nm
1,400 nm
Metaphase chromosome
In interphase cells most chromatin is in the highly extended form called euchromatin
Chromosome Number in Different Species
In "higher” organisms (diploids), members of same species typically have
identical numbers of chromosomes in each somatic cell. Diploid
chromosome number (2n). Nearly all chromosomes will exist in pairs
(identical wrt length and centromere placement) except the sex
chromosome Y. Members of pair are homologous chromosomes. Haploid
number (n) is the number of chromosome pairs.
Amount of genetic information in the chromosome can change
Deficiencies/Deletions
Duplications
Variation In Chromosome Structure
Single Chromosome Disorders 1. Deletion
2. Genetic material
1.Deletion
• Genetic material is missing
2. Duplication
• Genetic material is present twice
• is present twice
3. Inversion
A chromosomal deficiency occurs when a
chromosome breaks and a fragment is lost
Deficiencies (aka Deletions)
Phenotypic consequences of deficiency depends on
Size of the deletion
Functions of the genes deleted
Phenotypic effect of deletions usually detrimental
Deficiencies
Phenotypic consequences of duplications correlated to size & genes involved
Duplications tend to be less detrimental
Duplications
Bar-Eye Phenotype in Drosophila
• Phenotype: reduced number of ommatidia
• Ultra-bar (or double-bar) is a trait in which flies have even
fewer facets than the bar homozygote
• Both traits are X-linked and show intermediate dominance
Majority of small duplications have no phenotypic effect
However, they provide raw material for evolutionary change
Lead to the formation of gene families
A gene family consists of two or more genes that are
similar to each other
derived from a common gene ancestor
Well-studied example is the globin gene family
Genes encode proteins that bind oxygen
Duplications and Gene Families
A segment of chromosome that is flipped relative to
that in the homologue
Inversions
Centromere lies
within inverted
region
Centromere lies
outside inverted
region
Inversions
• No loss of genetic information
– Many inversions have no phenotypic consequences
• Break point effect
– Inversion break point is within regulatory or structural portion of a
gene
• Position effect
– Gene is repositioned in a way that alters its gene expression
– separated from regulatory sequences, placed next to constitutive
heterochromatin
• ~ 2% of the human population carries karyotypically
detectable inversions
Individuals with one copy of a normal chromosome and one
copy of an inverted chromosome
Usually phenotypically normal
Have a high probability of producing gametes that are abnormal in
genetic content
Abnormality due to crossing-over within the inversion interval
During meiosis I, homologous chromosomes synapse with
each other
For the normal and inversion chromosome to synapse properly, an
inversion loop must form
If a cross-over occurs within the inversion loop, highly abnormal
chromosomes are produced
Inversion Heterozygotes
Inversions Prevent Generation of Recombinant Offspring Genotypes
• Only parental chromosomes (non-recombinants) will produce normal progeny after fertilization
When a segment of one chromosome becomes
attached to another
In reciprocal translocations two non-homologous
chromosomes exchange genetic material
Usually generate so-called balanced translocations
Usually without phenotypic consequences
Although can result in position effect
Translocations
Fig. 8.13b(TE Art)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Nonhomologous chromosomes
Reciprocal translocation
1 1 7 7
Nonhomologous crossover
1 7
Crossover between nonhomologous chromosomes
Fig. 8.13a(TE Art)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
22
Environmental agent causes 2 chromosomes to break.
Reactive ends
22
2 2
DNA repair enzymes recognize broken ends and connect them.
Chromosomal breakage and DNA repair
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
In simple translocations the transfer of genetic
material occurs in only one direction
These are also called unbalanced translocations
Unbalanced translocations are associated with
phenotypic abnormalities or even lethality
Example: Familial Down Syndrome
In this condition, the majority of chromosome 21 is
attached to chromosome 14