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 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 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
