Demystified ...: Microsatellites

Abstract

Microsatellite DNA sequences consist of relatively short repeats of one to five base pair units; together with satellites and minisatellites they comprise a larger family known as tandemly repetitive sequences. Microsatellites are found both in prokaryotes and eukaryotes, including humans, wherein they appear scattered almost at random throughout the genome. Although in prokaryotes distinct biological functions have been demonstrated, the role of microsatellites in eukaryotes is less clear. Nevertheless, several interesting hypotheses exist suggesting that certain microsatellites may exert subtle influences on the regulation of gene expression. Although the presence of these subtle mechanisms may be beneficial to a whole population, when they go wrong, as is thought to happen in the case of human trinucleotide repeat associated diseases, such as Huntington's disease, the consequences for the individual can be fatal. Most human microsatellites probably have no biological use at all; however, they are extremely useful in such fields as forensic DNA profiling and genetic linkage analysis, which can be used to search for genes involved in a wide range of disorders. With a primary focus on humans, it is the aim of this review to present an up to date discussion, both of the biological aspects and scientific uses of microsatellite sequences. In the latter case, basic theoretical and technical points will be considered, and as such it may be of use both to laboratory and nonlaboratory based readers. (J Clin Pathol: Mol Pathol 2000;53:177-183) Keywords: microsatellites; genome; genetics; DNA Three billion may seem to be a very large number when used in any "normal" context. However, when used to refer to the number of repeating units of genetic information that are suYcient to encode the blueprint for something as complex as a human being, it never ceases to amaze me that this number is big enough! Consequently, it comes as even more of a surprise to find that most of these units appear to be "functionless junk"! In fact "functional DNA", consisting of transcribed genes and regions involved either in transcriptional regulation or in maintaining chromosomal structure/integrity, is thought to comprise less than a sixth of the total human genome. This observation immediately raises a considerable number of questions, namely: what is this genetic junk made up of? Is it really junk-does it truly possess no useful function either directly or indirectly? How is it acquired? What other types of organisms possess it? And can we make any use of it?Fully covering the questions raised above would provide more than ample scope for writing an entire book, and would extend well beyond the remit of this review. Nevertheless, even focusing as intended upon microsatellites and their relevance to humans, it should become clear that most of these questions remain ones that will require consideration, even if only in passing.Although only about 3% of the human genome encodes expressed protein sequences, the inclusion of non-expre...

Molecular marker‐based pedigrees for animal conservation biologists

“…Then, in the mid-1980s, came the biggest advance in the inference and use of pedigrees: the discovery of highly variable neutral genetic markers (e.g. microsatellites; Bennett, 2000) that allowed multilocus genetic fingerprinting of individuals (Jeffreys, Wilson & Thein, 1985). These molecular methods allowed the inference of relationships from genetic data rather than from observational data, which is often unreliable (Coltman et al, 1999).…”

Analysis of DNA Replication Intermediates Suggests Mechanisms of Repeat Sequence Expansion

“…Repeat sequences are distributed widely in all organisms, forming the micro-and mini-satellite regions of their chromosomal DNAs (1). Triplet repeat sequences have attracted particular attention, because they are involved in pathogenesis of at least 14 neurological disorders (2).…”

The origins of polypeptide domains

“…Small insertion-based polymorphisms are common and widely dispersed; (29,30,34) however there are few reports of the insertion of small sequence elements, either by duplication or other means, contributing to the successful genesis of novel polypeptide domains. (24,42,43,50) To determine whether insertion-based modification of functional domains was common, we examined the genes of the major histocompatibility complex (MHC).…”

“…One of these is the number of small repeats at a specific genomic location, in particular repeats of 1-6 nucleotides in length, termed microsatellites. (29) Microsatellite repeat number polymorphisms have been estimated to be up to five orders of magnitude more common than point mutations between individuals;(3) roughly 8% of all microsatellite repeats in the human genome are protein-coding. (31) Thus, at least in some species, repeat-based polymorphisms are likely the greatest source of proteincoding diversity between individuals within a population.…”