Animal Genetics

Mutation and genetic polymorphism

Mutation is the process by which the sequence of base pairs in a DNA molecule is altered. A mutation, then, is a change in either a DNA base pair or a chromosome.

A cell with a mutation is a mutant cell. If a mutation happens to occur in a somatic cell (in multicellular organisms), the mutant characteristic affects only the individual in which the mutation occurs and is not passed on to the succeeding generation. This type of mutation is called a somatic mutation. In contrast, mutations in the germ line of sexually reproducing organisms may be transmitted by the gametes to the next generation, producing an individual
with the mutation in both its somatic and its germ-line cells. Such mutations are called germ-line mutations.

The mutation rate is the probability of a particular kind of mutation as a function of time, such as the number of mutations per nucleotide pair per generation or the number per gene per generation.

The mutation frequency is the number of occurrences of a particular kind of mutation, expressed as the proportion of cells or individuals in a population,
such as the number of mutations per 100,000 organisms or the number per 1 million gametes.

Effects of Mutation:

Mutations can affect individuals in a variety of ways. Among the consequences of mutation are the following:

• Change in a morphological trait. Obvious change in some physical characteristic of an organism.
• Nutritional or biochemical variation. A mutation may occur in a gene that encodes an enzyme involved in a metabolic pathway, such as an enzyme involved in the biosynthesis of an amino acid. If this occurs, the organism can no longer synthesize the amino acid, and must obtain from dietary sources.
• Changes in gene regulation. If a mutation occurs in a gene encoding a transcription factor, it could affect when and where the genes controlled by that transcription factor are expressed. This will be addressed in the modules on gene regulation.
• Lethality. Some mutations are lethal to an organism.
• Change in behaviour.

Types of point mutations

 There are two basic types of mutations:

• base substitutions- this is the replacement of one base by another. For example, if a DNA molecule usually contains guanine at a certain position, but adenine takes the place of the guanine, then a base substitution has occurred. There are two types of base substitutions:
  • transitions - these involve the replacement of a purine with the other purine, or the replacement of a pyrimidine with the other pyrimidine.
  • transversions - these involve the replacement of a purine with a pyrimidine or vice versa.

• frameshift mutations- these change the reading frame of a gene. There are two types of framehift mutations:
  • insertions - as the name implies, these involve the insertion of one or more extra nucleotides into a DNA chain.
  • deletions - these result from the loss of one or more nucleotides from a DNA chain.

In an inverse mutation, a DNA sequence of nucleotides is reversed. Inversions can occur among a few bases within a gene or among longer DNA sequences that contain several genes.

Translocations are the transfer of a piece of one chromosome to a non-homologous chromosome. They are often reciprocal, with the two chromosomes swapping segments with each other.

The effects of small DNA changes depend on the region of the gene involved.

A. A nucleotide substitution in a coding region may be any of the following:

1. Silent or synonymous mutations consist in changing one codon for another that codes for the same amino acid; eg TTT (Leu) —> TTC (Leu).
2. Missense mutations involve a change of codons that cause substitution of one amino acid for another. E.g. Sickle cell hemoglobin: beta codon 6 GAG (Glu) —> GTG (Val).
3. Nonsense mutations involve change from one of the 61 codons that specify amino acids to one of the three termination codons. E.g. In the form of thalassemia common in the Mediterranean region, Hb beta thal-1, codon 17 AAG (Tyr) —> TAG (Ter). This causes premature termination of the protein chain.
4. Sense mutations involve change from a termination codon to one that codes for amino acids. E.g. Hemoglobin Constant Spring alpha 142 TAA (Ter) —> CAA (Gln). Translation continues beyond the normal termination until another termination codon is encountered.

B. Nucleotide substitutions can also affect the rate of transcription.

1. A change in the regulatory regions can abolish transcription.
2. In some instances, such as a mutation that causes persistence of fetal hemoglobin beyond the fetal period, nucleotide substitution in the 5' regulatory region causes the gene to be transcribed when it should be shut off.

C. Nucleotide substitutions can affect RNA processing.

1. Substitutions in the exon/intron boundaries can prevent normal splicing.
2. Substitutions within an intron or exon can create new splice sites.
3. Changes in the 3' direction (downstream) from the coding regions can interfere with addition of poly-A tail.

D. Insertion or deletion of one or two nucleotides destroys the reading frame. Such frameshift mutations cause absence of any functional gene product. The most common mutation that causes cystic fibrosis involves loss of three nucleotides, which leaves the reading frame intact but the protein is nonfunctional.

E. Many mutations that cause loss of gene function are deletions of larger numbers of nucleotides. E.g. Duchenne muscular dystrophy.

F. The mutations that occur at a particular locus may be quite heterogeneous. Some may knock out gene function completely, others may reduce the function, and still others may have no effect on the phenotype, i.e., they are normal variants. As a result of this heterogeneity, many patients described as "homozygous" for a recessive allele may actually be heterozygous for two different defective alleles. Such a person is often called a compound heterozygote.

Genetic polymorfism

Genetic Polymorphism A difference in DNA sequence among individuals, groups, or populations. Sources include SNPs, sequence repeats, insertions, deletions and recombination. (e.g. a genetic polymorphism might give rise to blue eyes versus brown eyes, or straight hair versus curly hair). Genetic polymorphisms may be the result of chance processes, or may have been induced by external agents (such as viruses or radiation). If a difference in DNA sequence among individuals has been shown to be associated with disease, it will usually be called a genetic mutation. Changes in DNA sequence which have been confirmed to be caused by external agents are also generally called "mutations" rather than "polymorphisms." [Source: PHRMA Genomics Lexicon]

Genetic Mutation A change in the nucleotide sequence of a DNA molecule. Genetic mutations are a kind of genetic polymorphism. The term "mutation," as opposed to "polymorphism," is generally used to refer to changes in DNA sequence which are not present in most individuals of a species and either have been associated with disease (or risk of disease) or have resulted from damage in°icted by external agents (such as viruses or radiation). [Source: PHRMA Genomics Lexicon]

Polymorphism at the protein level

Variations in the DNA sequences can be studied by protein polymorphism. But much genetic variation in the genome, in each case, remained undetected. Why?

• degeneracy in genetic code (64 codons, 61 code for 20 amino acids)
• substitution of similar amino acids might give an “identical” protein as far as the method of detection is concerned
• also, can only observe those proteins (allozymes) which can be separated on a gel after extraction and electrophoresis, and then can be detected.

Polymorphisms at the DNA level

• Restriction Fragment Length Polymorphisms (RFLPs)
• Minisatellites or VNTRs (Variable Numbers of Tandem Repeats)
• Microsatellites or SSRs (Simple Sequence Repeats)
• Single Nucleotide Polymorphisms (SNPs)

The document was created: 20. 01. 2021 21:34:33
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Prepared under project CZ.1.07/2.2.00/28.0020
Innovation of study programs FA MENDELU towards internationalization of study