A Polymorphic Microsatellite Repeat within the ECE-1c Promoter Is Involved in Transcriptional Start Site Determination, Human Evolution, and Alzheimer's Disease
Yaosi LiKerstin SeidelP. MarschallMichael KleinA. HopeJens SchacherlJennifer SchmitzMario MenkJan H. SchefeJana ReinemundRebecca HugelPeter WaldenAndreas SchlösserRudolf VolkmerJulia SchimkusHeike KölschWolfgang MaierJohannes KornhuberLutz FrölichSabrina KlareSebastian KirschKristin SchmerbachSylvia ScheeleUlrike GrittnerFrank S. ZollmannPetra Goldin-LangOliver PetersUlrich KintscherThomas UngerHeiko Funke‐Kaiser
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Genetic factors strongly contribute to the pathogenesis of sporadic Alzheimer's disease (AD). Nevertheless, genome-wide association studies only yielded single nucleotide polymorphism loci of moderate importance. In contrast, microsatellite repeats are functionally less characterized structures within our genomes. Previous work has shown that endothelin-converting enzyme-1 (ECE-1) is able to reduce amyloid β content. Here we demonstrate that a CpG-CA repeat within the human ECE-1c promoter is highly polymorphic, harbors transcriptional start sites, is able to recruit the transcription factors poly(ADP-ribose) polymerase-1 and splicing factor proline and glutamine-rich, and is functional regarding haplotype-specific promoter activity. Furthermore, genotyping of 403 AD patients and 444 controls for CpG-CA repeat length indicated shifted allelic frequency distributions. Sequencing of 245 haplotype clones demonstrated that the overall CpG-CA repeat composition of AD patients and controls is distinct. Finally, we show that human and chimpanzee [CpG] m –[CA] n ECE-1c promoter repeats are genetically and functionally distinct. Our data indicate that a short genomic repeat structure constitutes a novel core promoter element, coincides with human evolution, and contributes to the pathogenesis of AD.The results of our bioinformatics analysis have found over 91,000 di-, tri-, and tetranucleotide microsatellites in our survey of 25% of the X. tropicalis genome, suggesting there may be over 360,000 within the entire genome. Within the X. tropicalis genome, dinucleotide (78.7%) microsatellites vastly out numbered tri- and tetranucleotide microsatellites. Similarly, AT-rich repeats are overwhelmingly dominant. The four AT-only motifs (AT, AAT, AAAT, and AATT) account for 51,858 out of 91,304 microsatellites found. Individually, AT microsatellites were the most common repeat found, representing over half of all di-, tri-, and tetranucleotide microsatellites. This contrasts with data from other studies, which show that AC is the most frequent microsatellite in vertebrate genomes (Toth et al. 2000). In addition, we have determined the rate of polymorphism for 5,128 non-redundant microsatellites, embedded in unique sequences. Interestingly, this subgroup of microsatellites was determined to have significantly longer repeats than genomic microsatellites as a whole. In addition, microsatellite loci with tandem repeat lengths more than 30 bp exhibited a significantly higher degree of polymorphism than other loci. Pairwise comparisons show that tetranucleotide microsatellites have the highest polymorphic rates. In addition, AAT and ATC showed significant higher polymorphism than other trinucleotide microsatellites, while AGAT and AAAG were significantly more polymorphic than other tetranucleotide microsatellites.
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In this study, CT/AG microsatellite markers were separated using 5'anchored primer PCT in swimming crab genomic DNA. Among the 41 sequenced colons, 35(85.4%) sequences have microsatellites. Apart from some replications, 55 microsatellites were searched in 20 sequences. And 19 sequences have more than one microsatellite. The classifying for the repeat types of these microsatellites performed that among the 55 microsatellites, 27 microsatellites(50%) were CT/AG type and 27 were other types. The results showed that CT/AG microsatellite was abundant in P. trituberculatus; Additionally some other type microsatellites were isolated at the same time using 5'anchored primer. The selection efficiency was raised significantly.
Portunus trituberculatus
Primer (cosmetics)
genomic DNA
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In this experiment,magnetic bead hybridization method was used to enrich the microsatellite loci in Coelomactra antiquate.As a result,38 microsatellites that repeated no less than 5 times were found.Among the 38 microsatellites,68.4% are perfect,23.7% are imperfect and the rest are compound(7.9%).In addition to the biotin-labeled SRS(simple repetitive sequence) probe CA and GA,there are ATTG,TG,CGTG and TGTTG in the microsatellites.Microsatellite repeats mainly from 5 to 46 times,and the most repetitive number is 70.We designed 14 pairs of SSR-primers using these microsatellite sites,which will facilitate the studies on the genetic diversity of C.antiquata.
Magnetic bead
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New microsatellite markers were developed for Siamese crocodile (Crocodylus siamensis) by constructing a library for microsatellite DNA. Construction and characterization of the library are described in the present study. Twenty microsatellite markers were developed from a (AC)15 enriched microsatellite DNA library. Among the twenty microsatellite loci, ten (50%) were polymorphic, where as the rest were monomorphic (with two to four alleles per locus). The microsatellite sequences obtained could be classified structurally into perfect repeats (80%) and imperfect repeats (20%). No incomplete repeat type was observed. These markers were tested in five individuals of the same species and these tests resulted in twenty new microsatellites markers for C. siamensis. Low number of alleles (1-4 alleles) with an average of 1.7 alleles per locus was observed. The average length of uninterrupted repeats from the selected clones was 12.3.
Crocodylus
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A 5' anchored PCR was utilized to develop microsatellite markers in mango. Di-repeat primers containing 3 or 7 degenerate bases at the 5' end of the primers were used to amplify genomic DNA flanked by simple sequence repeats. The PCR products were cloned to generate enriched microsatellite libraries. Clones containing microsatellite fragments were randomly selected and subsequently sequenced. A specific primer was designed and used in combination with a 5' anchored primer to produce a locus-specific microsatellite marker. The results indicated that 7 degenerated bases of 5' anchored primers reduced the efficiency of 5' anchored PCR. Sixteen microsatellite markers were developed and were able to reveal 46 alleles in 8 mango varieties.
Primer (cosmetics)
genomic DNA
Mangifera
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Homology
R gene
Conserved sequence
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Dinucleotide Repeat
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Haliotis discus
Minisatellite
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Summary Microsatellite markers have been established for a large number of species, but up till now very few polymorphic microsatellite markers have been reported in poultry. We have isolated 34 polymorphic chicken microsatellite markers of the poly (TG) type. The number of repeats varied from 9 up to 33. Often, other repeats such as poly (T) or poly (GAA) were present adjacent to the poly (TG) repeat. Polymerase chain reaction amplification of the microsatellites resulted in detection of three or more alleles in a test panel of five different animals for 75% of the microsatellites. Segregation of five microsatellite markers has been tested in a small family.
Dinucleotide Repeat
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Microsatellites, also known as short tandem repeats (STRs) are short DNA sequences
containing repeated motifs ranging from 2-6 bases. The number of repeats varies between
individuals and the numbers occurring in a population are known as the alleles of a microsatellite.
Each individual carries two copies of each chromosome and hence two alleles
of each microsatellite. There are at least 250.000 microsatellites that have a known location
on a human reference genome, the most common form is dinucleotide repeats.
The range of applications for microsatellite analysis is very wide and includes among
other things medical genetics, forensics and genetic genealogy. However, microsatellite
variations are rarely considered in whole-genome sequencing studies in large due to a lack
of tools capable of analyzing them.
The goal of this thesis is to create a microsatellite genotype caller which is faster and
more accurate than others previously presented. In order to accomplish this goal two things
were examined. First, we reduce by 87% the amount of sequencing data necessary for creating
microsatellite profiles using previously aligned sequencing data. This was achieved
by filtering the input to contain only reads aligned to known microsatellite locations and
unaligned reads as these should be the ones useful for profiling. The results indicate that
when performing microsatellite profiling using previously aligned data it is possible to significantly
reduce running time with negligible effects on the resulting profile. Second, the
accuracy of the microsatellite profiler was increased from 87.5% to 96.3%. The improvements
included using population information to train microsatellite and individual specific
error profiles. This was done by adding parameters to the model as well as using sequencing
data from multiple individuals to improve parameter estimates. Combining these two
procedures we were able to give a practical implementation of microsatellite genotyping
which is both much faster and more accurate than previously presented solutions.
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