Molecular biologists had long known that natural populations have various alleles of genes. Considerable diversity was being fou
nd. For example, human blood types are controlled by several genes, each with different alleles (like blood type alleles A, B, O, etc.). That is a well known example, but in fact most genes exist in several alleles. How was this genetic diversity commonly viewed before the late 1960's?
Genetic variation in human populations can be studied with respect to specific genes or anonymous segments of DNA. During the 1960s and 1970s it was of major importance choosing random loci for assessing population.
According to https://www.ncbi.nlm.nih.gov/books/NBK100428/, "Allelic variation includes base substitution and simple insertion-deletion, as well as variation arising from varying numbers of a simple-DNA sequence motif. Historically, DNA polymorphisms were detected as restriction-fragment length polymorphisms (RFLPs) by using cloned DNA probes, either specific for genes or at anonymous genomic segments. RFLPs are due to base substitution or small insertion-deletion differences that lead to the creation or loss of a restriction-enzyme recognition site. RFLPs usually consist of 2 alleles with an average heterozygosity of 25% and were discovered primarily in northern Europeans in the process of constructing a human genetic-linkage map. They generally have known map locations in the human genome and low mutation rates. In attempting to search for yet more polymorphic markers, it was recognized that loci at which alleles differed in the number of repeated (tandem) copies of a core DNA sequence (16-72 base pairs) were common in the human genome and highly polymorphic. Several hundred of these variable-number tandem-repeat (VNTR) loci have been discovered and mapped in the human genome; they tend to be in telomeric chromosomal segments. VNTR loci generally have multiple alleles with an heterozygosity exceeding 70% but also a high mutation rate. Classical RFLP and VNTR loci are assayed with the Southern blotting method, which is tedious, is time-consuming, and requires 5 µg or more of DNA per assay. Although they have been extensively used for gene-mapping studies and in forensic applications, they have seen little use in human variation studies. It is unlikely that RFLPs and VNTRs will be used as in the past, because the assay requires a greater degree of technical skill, greater access to a cloned probe, and larger quantities of DNA than other contemporary methods."
