Cause by missegregation of a chromosome pair during meiosis. ex trisomy 21.
It produces chromosomal aneuploidy and are the most common mutation in human.
occuring 1/1700 cell division. Rarely pass to next generation due to its incompatible with survival or normal reproduction.
his is also frequently seen in cancer cell.
includes base pair substitution, insertions and deletions.
Orginate by either: errors introduced during the DNA replication; or mutations from a failure to repair DNA after damage.
Gene Muattion can be either spontaneous or introduced by Mutagens
he Origin of Mutations
- DNA Replication errors
- Repair of DNA damage
- Chain Termination
- RNA Processing
- Hotspot of mutation
A single nucleotide substitution( or point mutation) which alter the triplet code = missense.
Most of detected mutations are missense.
Other point mutation occurs either within or outside the code sequence of a gene can also have extensive effects.
ie: mutations in the 5' promoter region or the 3' untranslated region of the B globin gene lead to the sharp decrease of B-globin mRNA produced.
Chain Termination Mutations
cause: 1.mRNA carrying a premature and is unstable(nonsense-mediated mRNA decay), no translatio.
2. even if the RNA is stable enough to be translated, the truncated protein is usually unstable and degraded within the cell.
3. point mutation may also destory a termination codon and let translation to contiune until reach the next stop codon. such a mutation may disrupt any regulatory function on 3' end untranslated region downstream from normal stop codon.
RNA Processing Mutations
Transition s Transversion
Transition: Purine-Purine/Pyrimidine-Pyrimidine (A-G, G-A or C-T, T-C)
If random, Transversion vs Transition = 2:1
Large Deletions and Insertions
Alterations large enough to be dectected by Southern Blotting.
Single-nucleotide polymorphism (SNPs)
is a DNA sequence variation occurring when a single nucleotide — A, T, C, or G — in the genome
(or other shared sequence) differs between members of a species (or
between paired chromosomes in an individual). For example, two
sequenced DNA fragments from different individuals, AAGCCTA to AAGCTTA, contain a difference in a single nucleotide. In this case we say that there are two alleles : C and T. Almost all common SNPs have only two alleles.
Within a population, SNPs can be assigned a minor allele frequency — the lowest allele frequency at a locus
that is observed in a particular population. This is simply the lesser
of the two allele frequencies for single-nucleotide polymorphisms.
There are variations between human populations, so a SNP allele that is
common in one geographical or ethnic group may be much rarer in another. (wiki)
this class is result of indel between 2 to 100 nucleotides, 100 to 1000 in genome.
1/2 of all indels are simple b/c they have only 2 alleles.
The other half are mutiallelic due to variable numbers of a segment. This includes Microsatellite and Minisatellite.
=Short tandem repeat polymorphism(STRPs), are repeating sequences of 1-6 base pairs of DNA. Repeat one to few dozen times.
Microsatellites can be amplified for identification by the polymerase chain reaction (PCR) process, using the unique sequences of flanking regions as primers.
=variable number tandem repeats (VNTRs)
This class has many alleles due to variation in the number of copies of the minisatellite that are repaeted in tandem.
Method first used in DNA fingerprinting. Now use typing of microsatellites by PCR instead of detection by southern blotting.
（一）限制性片段长度多态性（Restriction Fragment Length Polymorphism，RFLP）