A tandem repeat in DNA is two or more contiguous, approximate copies of a pattern of nucleotides. Tandem repeats have been shown to cause human disease, may play a variety of regulatory and evolutionary roles and are important laboratory and analytic tools. Extensive knowledge about pattern size, copy number, mutational history, etc. for tandem repeats has been limited by the inability to easily detect them in genomic sequence data. In this paper, we present a new algorithm for finding tandem repeats which works without the need to specify either the pattern or pattern size. We model tandem repeats by percent identity and frequency of indels between adjacent pattern copies and use statistically based recognition criteria. We demonstrate the algorithm’s speed and its ability to detect tandem repeats that have undergone extensive mutational change by analyzing four sequences: the human frataxin gene, the human β T cell receptor locus sequence and two yeast chromosomes. These sequences range in size from 3 kb up to 700 kb. A World Wide Web server interface at c3.biomath.mssm.edu/trf.html has been established for automated use of the program.

/pdf/tandem-repeats-finder-a-program-to-analyze-dna-sequences-1oo3g6vnch.pdf

Tandem repeats finder: a program to analyze DNA sequences

https://www.cell.com/cell/pdf/0092-8674(92)90154-5.pdf

Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member

Attempts to study the genetic population structure of large mammals are often hampered by the low levels of genetic variation observed in these species. Polar bears have particularly low levels of genetic variation with the result that their genetic population structure has been intractable. We describe the use of eight hypervariable microsatellite loci to study the genetic relationships between four Canadian polar bear populations: the northern Beaufort Sea, southern Beaufort Sea, western Hudson Bay, and Davis Strait-Labrador Sea. These markers detected considerable genetic variation, with average heterozygosity near 60% within each population. Interpopulation differences in allele frequency distribution were significant between all pairs of populations, including two adjacent populations in the Beaufort Sea. Measures of genetic distance reflect the geographic distribution of populations, but also suggest patterns of gene flow which are not obvious from geography and may reflect movement patterns of these animals. Distribution of variation is sufficiently different between the Beaufort Sea populations and the two more eastern ones that the region of origin for a given sample can be predicted based on its expected genotype frequency using an assignment test. These data indicate that gene flow between local populations is restricted despite the long-distance seasonal movements undertaken by polar bears.

Microsatellite analysis of population structure in Canadian polar bears.

Genetic variation at hypervariable loci is being used extensively for linkage analysis and individual identification, and may be useful for inter-population studies. Here we show that polymorphic microsatellites (primarily CA repeats) allow trees of human individuals to be constructed that reflect their geographic origin with remarkable accuracy. This is achieved by the analysis of a large number of loci for each individual, in spite of the small variations in allele frequencies existing between populations. Reliable evolutionary relationships could also be established in comparisons among human populations but not among great ape species, probably because of constraints on allele length variation. Among human populations, diversity of microsatellites is highest in Africa, which is in contrast to other nuclear markers and supports the hypothesis of an African origin for humans.

High resolution of human evolutionary trees with polymorphic microsatellites

The normal development and maintenance of the prostate is dependent on androgen acting through the androgen receptor (AR). AR remains important in the development and progression of prostate cancer. AR expression is maintained throughout prostate cancer progression, and the majority of androgen-independent or hormone refractory prostate cancers express AR. Mutation of AR, especially mutations that result in a relaxation of AR ligand specificity, may contribute to the progression of prostate cancer and the failure of endocrine therapy by allowing AR transcriptional activation in response to antiandrogens or other endogenous hormones. Similarly, alterations in the relative expression of AR coregulators have been found to occur with prostate cancer progression and may contribute to differences in AR ligand specificity or transcriptional activity. Prostate cancer progression is also associated with increased growth factor production and an altered response to growth factors by prostate cancer cells. The kinase signal transduction cascades initiated by mitogenic growth factors modulate the transcriptional activity of AR and the interaction between AR and AR coactivators. The inhibition of AR activity through mechanisms in addition to androgen ablation, such as modulation of signal transduction pathways, may delay prostate cancer progression.

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Ranajit Chakraborty

Papers

Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups.