Week 11 Flashcards
(49 cards)
Major genome sequence variation
indels
translocaton
iversion
Duplication
a special subtype of insertions
they increase the copy number of genes
Large scale genome changes
Cytogenetics
PCR
DNA sequencing
Cytogenetics
What you can see down a microscope:
Karyotype
salivary gland giant chromosomes
Autosomes are organized based on size
Karytope chromosome types
depends on the location of the centromere
metacentric (middle centromere)
submetacentric (slightly before center)
acrocentric (closer to the one side)
telocentric (end of the chromosome)
human chromosome
no telocentric chromosomes
Drosophila giant polytene chromosomes
during salivary gland development cell division stops
DNA keeps replicating
homologs are aligned
protein associate differentially along the chromosomes creating a specific banding pattern when stained
PCR detection of genome variation
microsatellites or short tandem repeat
there can be variation at these loci due to slippage and translocation
use reverse PCR primers (2 on each strand) to detect the STRs
allows you to tell if an individual is heterozygous or homozygous for tandem repeats
Chromosomal deletions
multiple genes affected
effect on recombination frequency
complementation analysis
cytogenetics and PCR
If the deletion is large enough we can detect it in the karyotype
lethal when homozygous
Chromosomal deletion: effect on recombination frequency
decreases recombination frequency
if deletion is 10mu the map distance between two genes will decrease
Chromosomal deletion: effect on recombination frequency
decreases recombination frequency
if deletion is 10mu the map distance between two genes will decrease
Polytene chromosome deletions
because the homolohues align you get a bubble wt info not present on the chromosome forms a bulb
PCR analysis of chromosomal deletions
we get product from the deletion (primers designed for the deleted chromosome)
wt would be to long to detect
Chromosome duplications
Duplication are copy number variation that you can see through a microscope
Tandem duplication
Displaced duplication
Reverse duplication
Polytene chromosome duplication
duplicated homolog forms a bulge on the wt homolog
Use of duplication
allows us to test for haploinsufficiency
if the addition of the functional duplicated gene resues the phenotype we are dealing with haploinsufficient
Duplication of genes
increases gene dosage
Copy number variants in humans
estimated that between 5-10% of the human genomic sequence are copy number variants
smaller duplication
Copy number variants in humans
estimated that between 5-10% of the human genomic sequence are copy number variants
smaller duplication
origin of deletions and duplications
generally associated with recombination between repeated DNA sequence
transposons and other repeated sequences
genetic variation can be due to repetitive dna sequence recombining
Types of inversions
paracentric: around the centromere
pericentric inversion: inversions containing the centromere
Genes at breakpoints will be affected
genes can be split in half resulting in a null loss of function
genes can be linked to a new regulatory sequence resulting in gain-of-function
Effect of inversion on recombination frequency
any recombination within the inverted region results in non-viable gametes
only viable recombinants are going to occur just outside the inverted region
shrinks map distance between genes flanking the inversion
Non-reciprocal translocation
portion of the chromosome is duplicated into another chromosome
a displaced duplication
