Eukaryote Chromosomes Flashcards
The three kinds of VNTRs
Satellite - (>100) in centromere
Minisatellite - (15-100) dispersed
Microsatellite/SSR - (under 15) dispersed & telomere (repealed x1000s)
Microsatellites
Found in telomere and elsewhere
Mostly 2bp A/G repeats
Vertebrate telomeres - TTAGGG
Why are VNTRs variable in number? (3 reasons)
- Unequal crossing over between homo repeats
- DNA Rep Slippage (duplication/deletion)
- Repair of DNA Damage
What can DNA Replication Slippage Result in?
Leader = Duplication
Lagger = Deletion
What can we use VNTRs for?
Genetic Fingerprinting:
Predict Disease
Kinship Analysis
Forensic ID (11 microsatellite loci)
If using microsats - PCR Needed
Triplet Repeat Diseases
Caused by Length Variation in some microsats.
e.g. Fragile X (FMR1 Gene)
Repeat in 5’ Promoter (not Gene!!)
“Genetic Anticipation”
The number of repeats can be in a safe zone (4-50) but 200-2000 causes instability (mild phenotype) - more causes severe disease
Polyglutamine Diseases
Triplet Repeat Diseases specific to CAG repeats.
Occur in CODING regions.
Cause neurodegenerative disorders (e.g. Huntington’s)
How much of the human genome is repetitive?
About 50%
The Three types of Repeat Components
Gene Families
Interspersed Repeats
(incl. retrotransposons)
Tandem Repeats
What are the FOUR classifications of chromosomes?
Based on CENTROMERE position
Meta centric
Submetacentric
Acrocentric
Telocentric
An example of chromosome number variability?
The Chinese Muntjac
(23 ch)
and Indian Muntjac
(4 ch)
Number is uninformative
What does G-banding do?
Uses GIEMSA dye to stain AT-RICH (Gene-poor) regions
(Condensed heterochromatin areas)
Help differentiate similar chromosomes + show subdomains
What is FISH used for?
Map a gene on a chromosome
(Fluorescent “in situ” HYBRIDISATION)
Hyb a Fluoro labelled gene with a DNA region on the chromosome;
HOMOLOGY reveals location
What TWO kinds of chromosome abnormalities exist in humans?t
- NUMERICAL
Aneuploidy
Turner Monosomy
- STRUCTURAL
Chromosome rearrangement
What abnormalities do NOT happen in humans?
- Polyploidy -
Plants (large fruit, 8n strawberries)
Fish and amphibians
(Best have even number)
- Monosomy
(EXCEPTION: Turner Syndrome XO)
What are the human Sex Chromosome Trisomies?
- Kleinfelter XXY
(Tall and infertile) - Trisomy X
Tall, menstrual irregular
(XXX)
What are the three autosome trisomies?
- Down’s - 21
- Edwards - 18
- Patau - 13
What are the FOUR Chromosome rearrangement classes?
Inversion
Translocation
(Same or Diff)
Duplication
Deletion
Why do we get non-allelic HomoRec? (NAHR)
There are >1000 fixed segments of 10-50 kb
They are 5% of healthy genome
( ! ) What are FIVE potentially affected characteristics of Chrom Rearrangement?
Gene Dosage
Balance
Gene Disruption
Centromere
Meiosis
What two ways can rearranged chromosomes end up balanced?
- PARACENTRIC - no centromere change (switch on one arm)
2. PERICENTRIC - centromere moves but still balanced; meiosis problem
What is Robertsonian Translocation?
Two ACROCENTRIC chromosomes fuse at the centromere (keeping long arms!)
Teeny tiny chrom lost
Carrier would look normal but have meiosis problems
(OFFSPRING: normal, carrier, Down, lethal)
What is a Philadelphia chromosome?
A kind of RECIPROCAL translocation
Chrom 9 and 22
Long arms swap
Tiny Chrom (PHILLY) lost
What disease does Philly Chrom formation cause?
Chronic Myeloid Leukaemia
90% of cases
(Chrom 9 and 22)
What is an example of a Duplication disease?
Charcot-Marie-Tooth (CMT 1)
Duplicates gene PMP22
Decent with 2 dots in FISH
What are Copy Number Variations? (CNVs)
Just DELETIONS and DUPLICATIONS that aren’t microscopically visible
1kb - 5Mb
What do CNVs cause?
*further
Main source of human variations!
100% of pop have them
Cause cognitive, behaviour & congenital disorders
- Humans differ 8% of genome
- Changes risk of disease and response to some drugs
What is the C value Paradox?
That Genome Size (C)
≠ Complexity
C also ≠ No. of Genes
What is an example of the C Value Paradox?
Humans have 3.2 mil bp
Broad Beans have 5.2 mil bp
How does a Cot Curve reveal complexity?
Denature and team effort fragments -
Time ~ amount of COPIES
Faster = More Copies
How much of the human genome is Unique (non-abundant)
Just over 50%
30 - 75 % among euk
How much of human Unique Sequences actually encode protein?
only around 1.5%
Where are genes most concentrated?
Areas of high GC content
Other than genes, what else contributes to the unique component?
CpG islands
(Found in 2/3 of genes)
Promoters//Enhancers
(NC control sequences)
Introns
(NC intervening sequences)
What two categories of Repetitive DNA are there?
- INTERSPERSED repeats
- TANDEM repeats
- Gene families
Give 2 examples of gene families
- Beta-Globin Cluster
(5 genes and 2 pseudogene
- Histones
(Repeating unit)
How does the beta globin cluster work?
MAKES GLOBINS
(Five genes and 2 pseudogenes)
(Embryo > Foetal > Adult)
[ps]Epsilon»_space;
gamma G + gamma A»
[ps] Delta and Beta
How does the Histone family look?
H4 > H2B > H3 > H2A > H1
Repeating unit
What are the four kinds of interspersed repeats?
SINEs
LINEs
LTR
DNA Transposons
Briefly describe SINEs
300bp
Alu most abundant
10.6% genome
Processed pseudogne-
Uses nearby REVERSE TSase
Briefly describe LINEs
7000bp
L1 most abundant
17% of genome
Encodes REV TSase
How can retroTP elements be used for conservation?
Identifying species by their elements (shark fin soup)
What s accounts for about 15% of CNVs?
Interspersed sequence repeats
transposons
