Types of point mutations:
- 1. base-pair substitutions
- 2. indels
- 3. frameshifts
- 4. triplet repeats
- 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
- - Gnome
- - Chromosome
- - Gene
- - DNA Replication errors
- - Repair of DNA damage
- - Missense
- - 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
- =nonsense mutation
- 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.
Transition s Transversion
- Transition: Purine-Purine/Pyrimidine-Pyrimidine (A-G, G-A or C-T, T-C)
- Transversion: Purine-Pyrimidine
- 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）
- 到了广泛的应用。 RFLP基本原理：利用特定的限制性内切酶识别并切割不同生物个体的基因组DNA，得到大小不等的DNA片段，所产
- 小卫星DNA（Minisatellite DNA）又称数目可变串联重复序列（Variable Number of Tandem
- 并不广泛。 VNTR基本原理与RFLP大致相同，只是对限制性内切酶和DNA探针有特殊要求：(1)限制性内切酶的酶切位点必须不在
Copy Number Polymorphisms
- = CNPs.
- CNPs may have only two alleles or multiple alleles due to te copies (0,1,2,3...) of a segment of DNA in tandem.
- This have only be recently i.d. b/c deleted or repeated regions are too small to detect by cytogenetic examination but too large for DNA sequencing.
- Its discover by Array Comparative genome hybridization.
- A hereditary disorder that results in reduced production of the liver enzyme
- phenylalanine hydroxylase. This substance is involved in the breakdown
- of phenylalanine in food to tyrosine. Without a modified diet, affected
- infants will develop severe, irreversible brain damage.
Occurrence in a population of two or more alleles, usually at freq of 1% or higher.
Splice site mutation
Mutations that either destory the normal splicing site or create a new splice site at an inappropriate location.
DNA maker create by the tandem repeats of a DNA sequence of 6 to 100 nucleotides