Why are deletions and insertions of nucleotides likely

This type of variant results in a shortened protein that may function improperly, be nonfunctional, or get broken down. Insertion An insertion changes the DNA sequence by adding one or more nucleotides to the gene. Deletion A deletion changes the DNA sequence by removing at least one nucleotide in a gene. Deletion-Insertion This variant occurs when a deletion and insertion happen at the same time in the same location in the gene.

Duplication A duplication occurs when a stretch of one or more nucleotides in a gene is copied and repeated next to the original DNA sequence. Inversion An inversion changes more than one nucleotide in a gene by replacing the original sequence with the same sequence in reverse order. Frameshift A reading frame consists of groups of three nucleotides that each code for one amino acid. Repeat expansion Some regions of DNA contain short sequences of nucleotides that are repeated a number of times in a row.

Topics in the Variants and Health chapter What is a gene variant and how do variants occur? How can gene variants affect health and development? Do all gene variants affect health and development? Can a change in the number of genes affect health and development? Can changes in the number of chromosomes affect health and development? Can changes in the structure of chromosomes affect health and development?

Many chemical mutagens, some exogenous, some man-made, some environmental, are capable of damaging DNA. Many chemotherapeutic drugs and intercalating agent drugs function by damaging DNA.

Gamma rays, X-rays, even UV light can interact with compounds in the cell generating free radicals which cause chemical damage to DNA. Damaged DNA can be repaired by several different mechanisms. Sometimes DNA polymerase incorporates an incorrect nucleotide during strand synthesis and the 3' to 5' editing system, exonuclease, fails to correct it.

These mismatches as well as single base insertions and deletions are repaired by the mismatch repair mechanism. Mismatch repair relies on a secondary signal within the DNA to distinguish between the parental strand and daughter strand, which contains the replication error. Human cells posses a mismatch repair system similar to that of E.

Because DNA replication is semi-conservative, the new daughter strand remains unmethylated for a very short period of time following replication. This difference allows the mismatch repair system to determine which strand contains the error.

A protein, MutS recognizes and binds the mismatched base pair. DNA polymerase then fills in the gap and ligase seals the nick. An example is ACN encoding threonine. There are 13 codon "pairs", in which the nucleotides at the first two positions are sufficient to specify two amino acids.

A purine R nucleotide at the third position specifies one amino acid, whereas a pyrimidine Y nucleotide at the third position specifies the other amino acid.

The UAR codons specifying termination of translation were counted as a codon pair. The codons for leucine and arginine, with both a codon family and a codon pair, provide the few examples of degeneracy in the first position of the codon.

Degeneracy at the second position of the codon is not observed for codons encoding amino acids. Chemically similar amino acids often have similar codons. Hydrophobic amino acids are often encoded by codons with U in the 2nd position, and all codons with U at the 2nd position encode hydrophobic amino acids. The major codon specifying initiation of translation is AUG. Using data from the genes identified by the complete genome sequence of E.

AUG is used for genes. GUG is used for genes. UUG is used for genes. AUU is used for 1 gene. CUG may be used for 1 gene. Regardless of which codon is used for initiation, the first amino acid incorporated during translation is f-Met in bacteria. Of these three codons, UAA is used most frequently in E. UAG is used much less frequently. UAA is used for genes. UGA is used for genes. UAG is used for genes. The genetic code is almost universal. In the rare exceptions to this rule, the differences from the genetic code are fairly small.

Differential codon usage. Various species have different patterns of codon usage. The pattern of codon usage may be a predictor of the level of expression of the gene. In general, more highly expressed genes tend to use codons that are frequently used in genes in the rest of the genome. This has been quantitated as a "codon adaptation index". Thus in analyzing complete genomes, a previously unknown gene whose codon usage profile matches the preferred codon usage for the organism would score high on the codon adaptation index, and one would propose that it is a highly expressed gene.

Likewise, one with a low score on the index may encode a low abundance protein. The observation of a gene with a pattern of codon usage that differs substantially from that of the rest of the genome indicates that this gene may have entered the genome by horizontal transfer from a different species.

The preferred codon usage is a useful consideration in "reverse genetics". If you know even a partial amino acid sequence for a protein and want to isolate the gene for it, the family of mRNA sequences that can encode this amino acid sequence can be determined easily. Because of the degeneracy in the code, this family of sequences can be very large. Since one will likely use these sequences as hybridization probes or as PCR primers, the larger the family of possible sequences is, the more likely that one can get hybridization to a target sequence that differs from the desired one.

Thus one wants to limit the number of possible sequences, and by referring to a table of codon preferences assuming they are known for the organism of interest , then one can use the preferred codons rather than all possible codons.

This limits the number of sequences that one needs to make as hybridization probes or primers. Wobble in the anticodon. In contrast, the first two positions of the codon form regular Watson-Crick base pairs with the last two positions of the anticodon. This flexibility at the "wobble" position allows some tRNAs to pair with two or three codons, thereby reducing the number of tRNAs required for translation.

Wobble rules. Types of mutations. Base substitutions. Just as a reminder, there are two types of base substitutions. A frameshift mutation is a genetic mutation caused by a deletion or insertion in a DNA sequence that shifts the way the sequence is read. A DNA sequence is a chain of many smaller molecules called nucleotides. DNA or RNA nucleotide sequences are read three nucleotides at a time in units called codons, and each codon corresponds to a specific amino acid or stop signal. During translation, the sequence of codons is read in order from the nucleotide sequence to synthesize a chain of amino acids and form a protein.