VARIATIONS OF GENES: ALLELES
Genes that determine a person’s characteristics are found in particular locations on the 46 chromosomes. Each individual has two copies of each gene. One copy comes from the person’s father and the other copy comes from the mother. Some traits are determined by a single gene on one chromosome. Others, such as eye color, are determined by multiple genes at several locations. Simple observation of peoples’ eyes indicates that there must be considerable variation in these genes. Some people have brown eyes, others have blue or green eyes, and many people have eye colors that are intermediate between two or more of these. A more basic example of how gene inheritance works to produce a particular characteristic is with the ABO blood type. There are four different blood types in this system: A, B, O, and AB. Everyone has one of these types and there is a single gene that determines which type will be inherited from each parent. If a person inherits the same form of a gene from the mother and the father, that person is said to be homozygous with respect to that gene. For example, if a person inherits the type A form of the ABO gene from the mother and from the father, the person is homozygous AA. If, on the other hand, the person receives different forms of the same gene (A and B), then that person is said to be heterozygous; he or she has different forms of the genes for ABO blood type, and he or she will be type AB. Each form of a particular gene at a particular locus in the genome is called an allele. Thus, the A and B antigens are each alleles. In addition, some alleles are dominant, while others are recessive. If a person receives a dominant allele from one parent and a recessive allele from the other, the dominant one will usually prevail and the person will exhibit that characteristic. If there are a large number of such alleles, then the potential exists for a great deal of variation among human beings at this location (locus). This situation provides the basis for a DNA profile wherein the variation of alleles at several loci can be combined to provide a statistical evaluation of the likelihood of a particular set of alleles in a given population. What is meant by “different forms of an allele?” The observed characteristic expressed by the gene is called the phenotype. The observed blood type of a per son is his or her phenotype. The alleles that make up that gene constitute the geno type of the person. For example, a person with the genotype “AB” (inheriting the A gene from one parent and the B gene from the other) would have the phenotype AB. In DNA analysis, loci that are polymorphic are purposely chosen. These loci exhibit variation among members of a population. The more the variation at a locus, the more discriminating the analysis will be. For example, in the ABO blood system, type A blood is present in about 42% of the Caucasian population, type O is present in about 43%, type B is about 10%, and type AB in about 5%. Thus the locus for ABO blood type does show polymorphism, but by itself is not very discriminating, since even the rarest form of the gene would still include 5% of individuals as being the source of a blood sample. There are two types of variability in alleles. The first type is called sequence polymorphisms. An example is shown below. This type of sequence polymorphism is called a single nucleotide polymorphism (SNP).
The two sequences of double-stranded DNA are exactly the same except at the location indicated by the arrows. The other type of variation in DNA is called length polymorphism. Consider the following variation in a part of Lincoln’s Gettysburg Address:
Four Score and Seven Years
Ago Four Score and Seven Years Ago
Four Score and Seven Years Ago
Four Score and Seven Years Ago
These phrases are all the same except for the “and,” which repeats a different number of times in the various phrases. Now consider the length polymorphism that occurs in the short tandem repeat (STR) marker TH01 (T C A T or its complementary strand, A G T A). These four base repeating sequences is highly polymorphic. In the figure below, the sequence repeats twice:
The next figure shows the same sequence repeating four times:
The actual TH01 marker has between 3 and 14 repeats in the human genome. Because the repeats are right next to each other, without any intervening base pairs, these are referred to as tandem repeats. When variation in the number of repeats occurs from one individual to the next, then this locus is described as having a variable number of tandem repeats (VNTR). A person’s DNA type is a description of the type of alleles at all of the loci being analyzed on the genome.
