Human Chromosome Flashcards
What are the histone octamer core proteins?
8 total
Two each of H2A, H2B, H3, H4
How does DNA wrap around the nucleosome?
~250 bp wraps twice around this core, including a linker/spacer region
What interactions are involved in DNA wrapping around the nucleosome?
Electrostatic (negative DNA phosphates and positive histone Arg & Lys)
What is the most open and thus transcriptionally active form of compaction?
11nm nucleosome chromatin fiber, aka “beads on a string”
Formation of the 30nm transcriptionally silent fiberBe
Beads on a string wraps such that 6 nucleosomes arrange in a zigzag formation, twisting into the 30nm fiber
In the interphase nucleus, which is dark and which is light - hetero vs euchromatin
Heterochromatin is dark (transcriptionally silent)
Euchromatin is light (transcriptionally active)
Acetylation by ____ has what effect on chromosome compaction?
Acetylation by histone acetyltransferases (HATs) causes unwinding because the acetylation neutralizes the electrostatic stability
Methylation on chromosome compaction
Methylation prevents acetylation, thus promoting condensation
Deacetylation by ___ has what effect on chromosome compaction?
Deacetylation by HDACs maintains electrostatic stability, resulting in condensation.
HIstone phosphorylation on chromosome compaction
Phosphorylation adds negative charges to the histones, which would cause unwinding from the negative DNA.
Underlying cause of Rett Syndrome (neurodegenerative)
Mutation in MECP2, which binds methylated DNA in the brain to recruit HDACs and suppress gene expression.
Inactivating MECP2 causes a more open chromatin structure –> inappropriate gene expression –> neurodegenerative symptoms
G-banding
Stains A-T rich DNA, showing unique banding patterns
Metaphasic spread allows
Karyotyping of chromosomes, searching for gross aberrant chromosomal structures, diagnostic for a disease
C-banding
Visualizes centromere and heterochromatic regions of chromosomes 1, 9, 16, and Y. Useful for visualizing pericentric inversions
Euploidy
Normal complement of allelic chromosomes:
46 chromosomes: 22 autosomal chromosome pairs, one pair of sex chromosomes
Types of aneuploidy
- Nullisomy: missing pair of homologs (both alleles)
-
Monosomy: one chromosome is missing
- Partial monosomy: missing chromosome only partially deleted
- Triploidy: three entire homologous sets of chromosomes
- Tetraploidy
Differenc ein deteciton between aneuploidy and chromatin remodeling (like Rett’s)
Aneuploidy has early onset detection, even embryonic lethality; birth can come with clear developmental and/or neurological abnormalities.
Chromatin remodeling abnormalities has late onset (1st or 2nd yr) with progressive and/or neurodegenerative symptoms that get worse over time
If the missing chromosome in monosomy is an autosome, then ____
usually embryonic lethal, with the exception of Turner’s syndrome (45,XO)
Turner syndrome
45, XO
Female is missing oen of her two X chromosomes, resulting in edema, webbing, cardiovascular problems, slow growth, underdeveloped sexual development.
Trisomy of sex chromosomes…
minor problems (because we already have X-chromosome inactivation and the Y chromosome doesnt do anything anyway)
Trisomy 13 (Patau Syndrome)
Physical abnormalities - cleft lip/palate, clenched hands, polydactyly, microcephaly, micrognathia
Trisomy 16
Embyronic lethal in the first trimester; most common trisomy
Trisomy 18 (Edwards syndrome)
Same physical abnormalities as trisomy 13; more common in females
Trisomy 21 (Down’s)
Single msot common cause of birth defects; can range form mild to severe
