Week 5 Flashcards
mutation
change in genetic material. Can be spontaneous or induced
Germline mutation
mutation in gamete cells so the mutation is heritable.
Somatic mutations
mutation in nonreproductive cells. Usually isolated to the individual
induced mutations
are more common. Caused by mutagens or chemical/physical agents, radiation
How do mutagens disrupt pairing?
By modifying nucleotide structure
using base analogue similar to particular bases
by using Alkylating agents to create numerous DNA lesions
including interstrand cross-links.
How do mutagens interfere with replication?
by intercalating or inserting between bases and distort the helix
point mutations
affects only a single base pair
Missense
change in amino acid encoded
Frameshift mutation
shifts triplet reading of codons out of correct phase
Silent mutation
no change in amino acid encoded
deletion mutation
one or more missing nucleotides
Insertion mutation
One or more extra nucleotides present
Transversion mutation
purine to pyrimidine, or pyrimidine to purine
Transition mutation
Pyrimidine to pyrimidine, or purine to purine
Nucleotide substitution
one base pair in duplex DNA replaced with a different base pair
Gain of function mutation
expressed at incorrect time or in inappropriate cell types
Hypermorphic mutation
increases normal function
Spontaneous mutation
they occur in the absence of any known cause
conditional mutation
Expressed only under restrictive conditions
unconditional mutation
Expressed under permissive conditions as well as restrictive conditions
Hypomorphic mutation
reduces normal function
Loss of function mutation
eliminates normal function
nonsense mutation
creates translational termination codon
DNA repair requirements
DNA damage be detected and repair of DNA damage
Direct repair
Can reverse some damage i.e. UV damage
Excision repair
Altered DNA strand is removed and new segment synthesized “sledge hammer and duct tape”
Global nucleotide excision Repair
repair recognizes lessons anywhere in the genome
transcription-coupled nucleotide excision repair
preferentially repairs the transcribed strand of active genes
mismatch repair
A type of excision repair, it entails first the removal of the mismatched base pairs, then a replacement with the correct base pairs. The mismatch repair system preferentially corrects the base in the daughter strand following replication fork passage. MutH, MutS, and MutL proteins No specific sequence needed for it to find where to cut. The shape of the DNA is the indicator that there is something wrong
Base excision repair
removes bases damaged by oxidation, alkylation, and deamination. The damaged base is directly removed from the DNA • Glycosylase: breaks the covalent bond btwn the damaged base and the DNA strand Base removal triggers the excision and replacement of a stretch of DNA Abasic sites are repaired through this mechanism, with the exception of the first step: base excision • Base is already absent
Double strand breaks repair
repaired by 2 major pathways: Homologous recombination & non-homologous end joining (NHEJ)
Homologous recombination
occurs in meiosis to mix genes from maternal and paternal chromosomes before separating to form gametes o Depends on the presence of a homologous donor sequence that can be used to accurately replace sequences that may have been lost in the breakage
Non-homologous end joining
o When no homologous donor sequences are available, NHEJ is engaged. o Involves directly ligating ends of DNA strands o High risk of completely losing certain sequences prior to repair
Possible effects of repairing double stranded breaks
how the damage is repaired can sometimes lead to chromosome problems: • Deletions, inversions, translocations, chromosome-chromosome fusions, etc.
How will a double stranded break not have a deleterious effect?
In order for a double stranded break to not have a deleterious effect, it must not occur in a coding region, nor in a regulatory region, and it must have a homologous donor available (sister chromatid).
Chromosomal abnormalities
Frequently, chromosomal abnormalities are the result of breaks and subsequent repair events in critical regions of the genome
- Have their own short hand
- Can be numerical & structural
chromosome nomenclature
- Arms (sections on either side of the centromere) are defined as petite (p) or grande (q) • long (q) and short (p)
- Regions are numbered starting from the centrom ere and moving outward
- The bands in each region are numbered (again, moving outward from the centromere
Naming a chromsome
starts with the chromosome numbers, arm (p/q), region, and band
autosomes
chromosomes 1-22
Anatomy of a chromosome
Numerical (Anueploidy)
can be caused by a non-disjunction in Meiosis I or II. Polyploidy or Monosomy
polyploidy
more than 2 of any chromosomes
I.e. Trisomy 21 = Down Syndrome
Monosomy
Only 1 copy of a chromosome
i.e. Turner Syndrome: XO
Chromosome abnormality: Reciprocal
- Breakage of at least 2 chromosomes and exchange of the fragments
- Usually no deleterious effects in the carrier
- Issues arise during chromosome segregation in meiosis I
- Cannot form bivalents due to translocation
- Instead, form a complex called a pachytene quadrivalent
- Segregation pattern of the quadrivalent will determine how deleterious the effect will be for each resultant gamete
chromosome abnormality: Robertsonian
- Breakage of 2 acrocentric chromosomes near the centromere, and fusion of their long arms
- Also called ‘centric fusion’
- Short arms are lost
- Functionally is a balanced rearrangement
- Issues arise during chromosome segregation in meiosis I
chromosome abnormalities: deletions
Loss of part of a chromosome, resulting in monosomy for that portionof the chromosome
Duchenne muscular dystrophy: delXp21
Chromosomal abnormalities: insertions
Segment of one chromosome becomes inserted into another chromosome
If inserted material has moved from elsewhere in another chromosome then the karyotype is balanced
If material is duplicated within same chromosome compliment it is unbalanced
chromosomal abnormality: Mixoploidy
describes when there are 2 groups of cells in a single individual, each with a unique genetic makeup
mosaicism
You have a normal zygote and there’s a non-disjunction in one of the mitiotic divisions down the road
Chimerism
2 Single egg and single sperm combos fuse into one big blastula can form a chimera
Very rare
