Week 7 JP Content Flashcards
How are smears obtained
- Blood sample taken
- Cell induced to initiate mitosis
- blocked during metaphase
- stained with Giemsa dye
- observe under microscope
Def: Genome Structure
Includes chromosome number, size of chromosome, gene content, gene order
- Typically species specific
How is genome structure related to speciation?
Variations in chromosome number and/or structure are important forces driving speciation
Why do humans have a different chromosome number as chimpanzees?
Chromosome 12 and 13 fused to form chromosome 2 in humans
Is the human genome structure optimized through evolution?
- Optimized for current population under current conditions
- Not overall, will continue to evolve
- Different selection pressures in todays society
How are chromosomes organized within nucleus?
CHROMOSOMAL TERRITORY
- Gene-rich chromosomes: near the center
- Gene-poor chromosomes: near the periphery
INTERCHROMOSOMAL DOMAINS
- REGIONS BETWEEN TERRITORIES
Def: Karyotype
Organized visual display of chromosomes
- FISH and Giemsa staining help identification
FISH Karyotype
Florescent in situ hybridization
- Chromosomes shown through florescent probes
- Descending order of size and then sex chromosomes
P arm vs q arm
Short arm vs long arm
Standardized Human Chromosome Map
- Obtained using Giemsa staining and microscope
- Regions that contain actively expressed genes and are less condensed are called euchromatin - tend to be GC rich and strain lightly
- Regions that are tightly condensed and contain fewer expressed genes are called heterochromatin - AT rich and stain more heavily
- Distances on chromosome measured from centromere
What causes genome structure changes?
Nondisjunction
Def: Nondisjunction
The failure of chromosomes and sister chromatids to properly separate during cell division
At what stage does nondisjunction occur
- Germline cells: meiosis I / meiosis II
- Somatic cell: mitosis
What is the result and consequences of nondisjunction
- Abnormalities in chromosome number - aneuploidy and polyploidy
- Causes dosage imbalance: generally more severe fitness effects in animals than plants
Klinefelter Syndrome
XXY
BABIES
- Weak muscles
- slow motor development (taking longer then average to crawl and walk
- Delay in speaking
- testicles not descended into the scrotum
ADULTS
- Low sperm count or no sperm
- low sex drive
- less muscular compared with other men
- increased belly fat
- small testicles and penis
- taller than average height
- decreased facial and body hair
- enlarged breast tissue
Trisomy 13
PATAU SYNDROME
Mental retardation and developmental delay, possible deafness, major organ abnormalities and early death
Trisomy 18
EDWARD SYNDROME
Mental retardation and developmental delay, skull and facial abnormalities, early death
Trisomy 21
DOWN SYNDROME
Mental retardation and developmental delay, characteristic facial abnormalities, short stature, variable life span
XYY
JACOB SYNDROME
Tall stature, possible reduction but not loss of fertility, no impact on mental capacity
XXX
TRIPLE X SYNDROME
Tall stature, possible reduction of fertility, menstrual irregularity, no impact on mental capacity
XO
TURNER SYNDROME
No secondary sexual characteristics, infertility, short stature, webbed neck, no impact on mental capacity
Def: Polyploidy
> 3 sets of chromosomes in the nucleus of an organism
Autopolyploid
DUPLICATION OF OWN DNA
1. Meiotic whole-genome nondisjunction: diploid gamete
2. Mitotic whole-genome nondisjunction
3. Mitotic and meiotic non-disjunction combined
Alloployploidy
Combining the chromosome sets of different species through hybridization
What kind of benefits can we obtain from polyplodization?
- Bigger fruits and flowers
- Fertility is decreases - particularly in 3n, 5n etc.
- Hybrid vigor in allopolyploids
- Polyploidization as a mechanism for rapid speciation
How do chromosome structures change?
- Chromosome Breakage
- unequal crossover during meiosis
Chromosome breakage
Changes chromosome structures leading to
- Missed ligation - loss of chromosome segments (deletion)
- Duplication ligation - gain of chromosomes (duplication)
Terminal deletion
Chromosome break that detaches part of one arm
- contains telomere and some genetic material
Accentric fragment
Broken off fragment without centromere that can be lost during cell division
Interstitial deletion
the loss of an internal segment of a chromosome that results from two chromosome breaks followed by a joining of the ends on either side of the segment
Consequence of unequal crossover during meiosis
- Partial deletion heterozygote
- Partial duplication heterozygote
How does unequal crossover during meiosis occur
- Homologs misalign and a copy of gene loops out on each chromosome
- when recombination occurs both loops on one side and neither on the other
- leads to deletion on one side and duplication on the other
How do we detect duplication and deletion?
- FISH probes to certain genes
- No fluorescence detected from probe B - deletion (microinterstitial deletion)
- Two fluorescent spots indicate the target of probe B is duplicated (microduplication)
Microdeletions and microduplications
- smaller
- not easy to detect by chromosome banding analysis
- Use FISH to detect absence or presence of a particular gene or chromosome sequence
Chromosome inversion
Wrong orientation of segment in the same chromosome
Chromosome Translocation
Segment in a different chromosome
How are inversion and translocations generated?
Caused by chromosome breakage and wrong reattachment
- if no critical gene or regulatory region is broken or in the inverted/translocated regions, there may be no phenotypic consequences
- In germline cells they can affect chromosome segregation and reduce fertility during meiosis
Types of chromosome inversion
- Paracentric inversion: centromere outside of inverted region
- Pericentric inversion: centromere within inverted region
Inversion heterozygotes
have one normal and one inverted homolog
How does paracentric inversion influence crossing over and fertility?
- Forms inversion loop at synapsis
- Crossing over that occurs outside the inverted region takes place normally
- Crossing over within the inverted region results in duplications and deletions in the recombinant chromosomes: forms a dicentric chromosome (non-viable) and an acentric fragment (lost in subsequent division)
How does pericentric inversion influence crossing over and fertility?
- Crossing over that occurs within a pericentric inversion results in both duplicated and deleted regions in both of the recombinant products
- Recombination event yields two normal gametes (from the non-crossover chromatids) and 2 abnormal (from crossover)
What is chromosomal translocation?
Broken ends of nonhomologous chromosomes are reattached, three types
- unbalanced
- reciprocal balanced
- Robertsonian translocation
Unbalanced translocation
Break off from one chromosome transferred to another causing deletion and addition
Reciprocal balanced translocation
translocation swap in two non-homologous chromosomes
Robertsonian translocations
AKA chromosomal fusion
- translocation of whole arm resulting in loss of other centromere due to lack of genes and fusion of the nonhomologous chromosomes
Translocation heterozygotes
may experience semisterility due to segregation abnormalities
What are the consequences of balanced reciprocal translocation?
- Somatic cells: usually no observed effect
- Germline cells: 1/2 normal, 1/2 inviable
How is chromosomal DNA packaged inside the nucleus
- Chromosome: 50% DNA, 50% protein
Proteins: - 50% histone proteins (H1, H2A, H2B, H3, H4)
- two molecules of histones H2A, H2B, H3 and H4 (octamer) form nucleosome core particles
- 146 bp wraps around each octamer to form nucleosome
- remaining 50% of protiens are diverse combination of enzymes, transcription factors etc.
Solenoid Structure
10-nm fiber coils and forms the solenoid structure (30nm fiber), with 6-8 nucleosomes per turn and histone H1 stabilizing the solenoid
Interphase chromosome orgnaization
30-nm fibers attached to nonhistone scaffolding proteins at sites called MAR (matrix attachment regions), forming chromatid loops
- chromosome scaffolding gives chromosomes their shape
- the loops on the scaffolds are about 300nm which coil again to form chromosome arm
Why are DNA packaged into scaffolds and chromatids?
- Efficient storage and separation of chromosome’s at anaphase
- Chromatin loops play a role in the regulation of gene expression
- Active transcription take place in segments of loops distant from MARs
- Euchromatin (big loops, transcription is high) vs heterochromatin (small loops, low transcription activity
What is the total length of DNA in a human
7.59 x10^9 km
