Dna Sequence Variations Mutation Andor Polymorphism

As noted earlier, only approx 5% of the approx 3 billion basepairs that constitute the human genome codes for proteins. Scientists have begun to understand the significance of the sequences that comprise the remaining 95%. One interesting aspect of these noncoding sequences is the amount of interindividual variation that these sequences exhibit. In some cases, these sequence variants are the result of mutation, the random alteration of DNA. When two or more sequence variants are present in a given population with a frequency of greater than 1%, then they are said to be polymorphic. At the molecular level, DNA polymorphism refers to differences in nucleotide sequences between two chromosomes at a particular genetic locus (Fig. 2A). A locus designates the position or location of a gene sequence on a chromosome; different versions of the gene at a particular locus are called alleles. Because autosomes contain two sets of chromosomes, each gene is present in two copies. Therefore, an individual can have two identical versions, or alleles, of a given gene, or can have different alleles. Homozygosity refers to having the same allele of a given gene present on both chromosomes; heterozygosity refers to having different alleles (Fig. 2B).

Genetic polymorphism is a normal occurrence, usually without grave consequences, that contributes to those traits that establish our individuality. The first types of polymorphism to be described were those that resulted in fragment length variations when DNA was digested with restriction endonucleases. These enzymes cleave DNA at specific recognition sites, producing smaller DNA fragments. Restriction fragment length polymorphisms (RFLP) occur when a restriction endonuclease recognition sequence varies between alleles at the same locus within an individual or between individuals at the same locus (Fig. 3). These variations are commonly referred to as sequence polymorphisms, because a single nucleotide within a particular DNA sequence is changed. A second type of polymorphism consists of hypervariable regions of DNA characterized by many copies of the same DNA sequence; these polymorphisms result in changes in the length of a particular sequence, as more copies are incorporated. Minisatellite sequences were the first of these types of polymorphism to be identified and are referred to as variable numbers of tandem repeats (VNTRs); VNTRs can be from 10 to 100 bp in length (Fig. 4) (11). Microsatellites, or short tandem repeats (STRs), consist of dinucleotide, trinucleotide, and tetranucleotide repetitive sequences distributed throughout the genome with a frequency

Fig. 3. Restriction fragment length polymorphism analysis for alleles 1 and 2 of a given genetic sequence. Allele 1 has restriction enzyme recognition sequences that are invariant (solid bar) and variant (*). This variant site is the site of the sequence polymorphism. When digested with the enzyme, 5.0-kb and 2.2-kb fragments are detected by gel electrophoresis and probe hybridization. In contrast, allele 2 contains only the two invariant sites. Thus, after restriction enzyme digestion, only a 7.2-kb fragment is detected.

Fig. 3. Restriction fragment length polymorphism analysis for alleles 1 and 2 of a given genetic sequence. Allele 1 has restriction enzyme recognition sequences that are invariant (solid bar) and variant (*). This variant site is the site of the sequence polymorphism. When digested with the enzyme, 5.0-kb and 2.2-kb fragments are detected by gel electrophoresis and probe hybridization. In contrast, allele 2 contains only the two invariant sites. Thus, after restriction enzyme digestion, only a 7.2-kb fragment is detected.

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Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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