Genes VII

Sequences that resemble satellites in consisting of tandem repeats of a short unit, but that overall are much shorter, consisting of (for example) from 5 V50 repeats, are common in mammalian genomes. They were discovered by chance as fragments whose size is extremely variable in genomic libraries of human DNA. The variability is seen when a population contains fragments of many different sizes that represent the same genomic region; when individuals are examined, it turns out that there is extensive polymorphism, and that many different alleles can be found.

These sequences are called minisatellite or VNTR (variable number tandem repeat) regions. The cause of the variation is that individual alleles have different numbers of the repeating unit. For example, one such minisatellite has a repeat length of 64 bp, and is found in the population with the following distribution:

 7% 18 repeats

11% 16 repeats

43% 14 repeats

36% 13 repeats

4% 10 repeats

The cause of this variation is genetic recombination between misaligned repeat units, in the same way that we have discussed already for satellite DNA. The rate of genetic exchange at minisatellite sequences is high, ~10 ^V4 per kb of DNA. (The frequency of exchanges per actual locus is assumed to be proportional to the length of the minisatellite.) This rate is ~10 greater than the rate of homologous recombination at meiosis, that is, in any random DNA sequence. So minisatellites may be hotspots for meiotic recombination.

Sometimes the presence of a minisatellite is correlated with a high rate of exchange in the vicinity, but in some cases the recombination event occurs between sister chromatids. In the latter case it changes the length of the minisatellite, but has no effect on flanking markers, because these are identical on both recombining molecules of DNA.

The high variability of minisatellites makes them especially useful for genomic mapping, because there is a high probability that individuals will vary in their alleles at such a locus. An example of mapping by minisatellites is illustrated in Figure 4.22. This shows an extreme case in which two individuals both are heterozygous at a minisatellite locus, and in fact all four alleles are different. All progeny gain one allele from each parent in the usual way, and it is possible unambiguously to determine the source of every allele in the progeny. In the terminology of human genetics, the meioses described in this figure are highly informative, because of the variation between alleles.

One family of minisatellites in the human genome share a common "core" sequence. The core is a G EC-rich sequence of 10 V15 bp, showing an asymmetry of purine/pyrimidine distribution on the two strands. Each individual minisatellite has a variant of the core sequence, but ~1000 minisatellites can be detected on Southern blot by a probe consisting of the core sequence.

Consider the situation shown in Figure 4.22, but multiplied 1000 . The effect of the variation at individual loci is to create a unique pattern for every individual. This makes it possible to assign heredity unambiguously between parents and progeny, by showing that 50% of the bands in any individual are derived from a particular parent. This is the basis of the technique known as DNA fingerprinting.