1. Higher Eukaryotic Chromosomes Flashcards
Explain chromosome anatomy
- telomeres
- centromere
- sister chromatids
- short (p) / long (q) arm
Explain terms sister chromatids, centromere, telomeres
- Sister chromatids: indentical copies of a chromosome - formed by replication - joined by centromere
- Centromere: constricted region on a replicated chromosome - kinetochores assembles - spindle fibers attach
- Telomeres: chromosome end regions - contain repetitve DNA seq. - stable + don’t fuse with other telomeres
Explain human karyotype
Human karyotype:
- 23 pairs of homologous = 46 chromosomes
- 44 autosomes + 2 sex chromosomes
- Assebled largest -> smallest (1- largest, 21 - smallest) + sex chromosomes
Explain what is a karyotype
Karyotype: a set of chromosomes unique to an organism’s cells
Why is the chromosome number uninformative in comparing organisms?
Chromosome number /gene number doesn’t relate to organism complexity:
- burds 39
- human 46
- kidney bean 5.2x10^9 genes
- human 3.2x10^9
Does chromosome number remain similar in similar organisms?
Not necessarily - Muntjac genus
23 vs 4
What are the possible chromosome classifications based on centromere position?
- Metacentric
- Submetacentric
- Acrocentric
What is secondary constriction chromosome?
Secondary constriction: narrower region on chromosome arms - centromere is primary constriction
Satellite chromosomes (SATs) - in humans associated with chrom. 13, 14, 15, 21, 22
Secondary constrictions can act as NORs
What are nucleolar organization regions (NORs)?
NORs: chromosomes segments - contain the genes for rRNA - give rise to the interphase nucleoli
NORs - secondary constrictions
How can similar size chromosomes be distinguished?
By staining - banding pattern - distinct for each chromosome
- Giemsa
- FISH mapping
Explain G-banding
Chromosome staining method
- Giemsa stain
- light (GC rich - gene rich)
- dark bands (AT rich, gene poor)
Explain FISH gene mapping
For mapping genes on chromosomes:
- specific sequence complimentary hybridization with fluorescent probe
Can chromosomes be labelled not at metaphase?
Yes, interphase chromosome territories labelled by FISH
What is digital karyotyping?
Digital karyotyping: for quantifying gene copies in genome
What are the types of chromosome abnormalities?
- Numerical abnormalities (polyploidy, aneuploidt, monosomy, trisomy)
- Structural abnormalities (gene rearrangements)
Explain polyploidy, aneuploidy, monosomy, trisomy
-Polyploidy: 1+ additional chromosomes in each pair -> 3n humans not viable but common in fish, plants
- Aneuploidy: loss/gain of genetic material in single chromosome
- Monosomy: loss of one chromosome in karyotype (2n-1)
- Trisomy: gain of one chromosome in karyotype (2n+1)
What is the most common cause of most enuploidy?
Non-disjunction during gamete meiosis
What are the possible causes of aneuploidy in humans?
- Tolerated in sex chromosomes - gene dosage
- Not tolerated in autosomes - unbalanced genomes => spontaneous miscarriage (aborts itself if chromosome abnormality)
What are the possible chromosome rearrangements causing structural chromosome abnormalities?
Chromosome rearrangements:
- duplication
- deletion
- inversion
- translocation
Which chromosome rearrangements are balanced and unbalanced?
- Unbalanced: duplication / deletion - too little / many genes
- Balanced: translocation - gene dosage stays the same - location changed (ex inversion)
=> inversion better tolerated than duplications/deletions
(duplication not the same as insertion - here DUPLICATION)
Explain non-homologous end joining (NHEJ)
NHEJ: repairs ds DNA breaks- break ends are directly ligated without homologous template
In contrast: homology directed repair (HDR) - requires a homologous sequence to guide repair
Explain how gene duplication / deletion occurs
Duplication / deletion occurs between LCRs - double stranded chromosome break - exchange -> recombined duplication / recombined deletion => unbalanced gene dosage
=> duplications / deletions cause disease - protein overexpression / underexpression due to changed gene repeat # - unbalanced gene dosage
What are low copy repeats (LCRs)?
Low copy repeats (LCRs): regions of duplicated DNA - more than 1 kb in size - share a sequence similarity >90%
On chromosomes - LCR hotspots - majority of duplications / deletions occur
Explain how gene translocation occurs
Translocation: chromosome breaks - fragmented pieces re-attach to different chromosomes
Most common chromosome rearrangement - carriers healthy and fertile
What are the types of chromosome translocations?
- Reciprocal translocations (adjacent / alternate segregation)
- Robertsonian translocations
What are reciprocal chromosome translocations?
Reciprocal: genetic exchange between non-homologous - parts of chromosome arms exchange genes (not whole arms exchanged)
What are the different outcomes of different chromosome translocations?
Depends how chromosomes segregate and which separation axis form in meiosis
1. Adjacent segregation - horizontal=> unbalanced - could be viable
2. Adjacent segregation - vertical => unbalanced - unviable
3. Alternate segregation => balanced / normal - viable
Explain Robertsonian translocation
Robertsonian: genetic exchange between non-homologous acrocentric chromosomes - centric fusion
=> two chromosomes form one large fused chromosome -> depending on gamete which is used for fertilization - effect size (diff final gametes)
Because p arm so small - main genes in q - if p lost => still balanced translocation
How can Down syndrome be caused by Robertsonian translocation?
Because q arm has all the important genes in acrocentric chromosomes - Robertsonian translocated chromosome -> third repeat of same genes -> trisomy
However - only 3.5% of Down syndrome caused by Robertsonian translocation - majority caused by nondisjunction
Explain what is Philadelphia chromosome
Philadelphia chromosome (22q-): made in chromosome translocation between 9q and 22q - BCR+ABL gene fusion -> BCR+ABL fusion protein => chronic myeloid leukemia (CML)
Philadelphia chromosome can be diagnosed by karyotyping - FISH BCR and ABL genes - if together on one chromosome => CML
Example: chromosome abnormalities visible in karyotyping
Used FISH
What are copy number variations (CNVs)?
Copy number variations (CNVs): general term used to describe repeated genome sequences
- the number of repeats varies between individuals of same species
- associated with many phenotypes
- duplications in tandem - CNVs often rely on fixed segmental duplications
What are the types of CNVs?
- Short repeats
- Long repeats (if one repeat mutates - the correct protein still produced)
What is segmental duplication?
Segmental duplication: chromosome rearrangement in which a whole gene segment is duplicated rather than only one gene
- Fixed segmental duplications generate non-essential genes - can evolve + generate further de novo rearrangements
- Example: in Asia starch very common in culture diet - asians have more AMY1 amylase enzyme repeats - advantage -> low repeat # releates to obesity
What is de novo in biology?
What are fixed meiotic rearrangements?
Fixed meiotic rearrangement: chromosome rearrangement passed to the next generation
- Karyotypes evolve via fixed meiotic rearrangements
What is synteny and syntenic genes?
Synteny: conserved order of similar gene blocks in different species
Syntenic genes: genes arranged in same blocks in different species
- Species that share synteny - common ancestor
How can syntenic chromosomes be identified experimentally?
Cross species chromosome painting - ZOO FISH: detects conserved synteny - shared ancestry for chromocomal blocks
- one species’ sequences used as probes for the other spiecies sequence -> if diff colour on chromosome -> syntenic chromosomes - same common ancestor
What is the ancestral eutherian karyotype?
Ancestral eutherian karyotype: n = 22 + X; the MRCA to the human karyotype and cattle lineages
- Karyotype analysis between species can help determine evolutionary relationships
Human chromosome blocks in ancestral karyotype
Lecture summary + keys terms
Explain pericentric vs paracentric inversion
Paracentric: inversion doesn’t involve the centromere - inverted segment exclusive to p / q arm -> no change in length of arms
Pericentric: inversion involves both p + q arms and centromere -> change in length of arms
Detailed prokaryotic vs eukaryotic gene structure
https://microbenotes.com/gene-a-comprehensive-guide/
What is non-allelic homologous recombination?
NAHR: HR that occurs between two lengths of DNA that have high sequence similarity, but are not alleles
