Genetics and genomics of core short tandem repeat loci used in human identity testing.
TL;DR: The physical location of each STR locus in the human genome is delineated and allele ranges and variants observed in human populations are summarized as are mutation rates observed from parentage testing.
Abstract: Over the past decade, the human identity testing community has settled on a set of core short tandem repeat (STR) loci that are widely used for DNA typing applications. A variety of commercial kits enable robust amplification of these core STR loci. A brief history is presented regarding the selection of core autosomal and Y-chromosomal STR markers. The physical location of each STR locus in the human genome is delineated and allele ranges and variants observed in human populations are summarized as are mutation rates observed from parentage testing. Internet resources for additional information on core STR loci are reviewed. Additional topics are also discussed, including potential linkage of STR loci to genetic disease-causing genes, probabilistic predictions of sample ethnicity, and desirable characteristics for additional STR loci that may be added in the future to the current core loci. These core STR loci, which form the basis for DNA databases worldwide, will continue to play an important role in forensic science for many years to come.
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TL;DR: High-resolution DNA melting has several advantages over other genotyping and scanning methods, including an inexpensive closed tube format that is homogenous, accurate and rapid, and a good fit for personalized medicine as a rapid, inexpensive method to predict therapeutic response.
Abstract: High-resolution melting of DNA is a simple solution for genotyping, mutation scanning and sequence matching. The melting profile of a PCR product depends on its GC content, length, sequence and heterozygosity and is best monitored with saturating dyes that fluoresce in the presence of double-stranded DNA. Genotyping of most variants is possible by the melting temperature of the PCR products, while all variants can be genotyped with unlabeled probes. Mutation scanning and sequence matching depend on sequence differences that result in heteroduplexes that change the shape of the melting curve. High-resolution DNA melting has several advantages over other genotyping and scanning methods, including an inexpensive closed tube format that is homogenous, accurate and rapid. Owing to its simplicity and speed, the method is a good fit for personalized medicine as a rapid, inexpensive method to predict therapeutic response.
653 citations
TL;DR: A list of known cross‐contaminated cell lines is compiled, drawn from 68 references, and it is essential to check the sample itself by performing authentication testing, even if there are no previous publications on cross-contamination for that cell line.
Abstract: Continuous cell lines consist of cultured cells derived from a specific donor and tissue of origin that have acquired the ability to proliferate indefinitely. These cell lines are well-recognized models for the study of health and disease, particularly for cancer. However, there are cautions to be aware of when using continuous cell lines, including the possibility of contamination, in which a foreign cell line or microorganism is introduced without the handler's knowledge. Cross-contamination, in which the contaminant is another cell line, was first recognized in the 1950s but, disturbingly, remains a serious issue today. Many cell lines become cross-contaminated early, so that subsequent experimental work has been performed only on the contaminant, masquerading under a different name. What can be done in response—how can a researcher know if their own cell lines are cross-contaminated? Two practical responses are suggested here. First, it is important to check the literature, looking for previous work on cross-contamination. Some reports may be difficult to find and to make these more accessible, we have compiled a list of known cross-contaminated cell lines. The list currently contains 360 cell lines, drawn from 68 references. Most contaminants arise within the same species, with HeLa still the most frequently encountered (29%, 106/360) among human cell lines, but interspecies contaminants account for a small but substantial minority of cases (9%, 33/360). Second, even if there are no previous publications on cross-contamination for that cell line, it is essential to check the sample itself by performing authentication testing.
422 citations
Cites background from "Genetics and genomics of core short..."
...It is primarily for this reason that STR profiling is recommended as an international reference standard for human cell lines(26) and accepted within the legal system for human identity testing.(39) STR profiling is based on the presence of STRs within the human genome that exist at variable lengths throughout the population....
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Book•
03 Sep 2009
TL;DR: The basic principles of Forensic DNA Typing and its applications in medicine, science and research are studied.
Abstract: Fundamentals of Forensic DNA Typing , Fundamentals of Forensic DNA Typing , کتابخانه دیجیتال جندی شاپور اهواز
310 citations
TL;DR: Although several methodological changes have facilitated profiling from trace samples in recent years it is also clear that many opportunities exist for further improvements.
Abstract: DNA analysis is frequently used to acquire information from biological material to aid enquiries associated with criminal offences, disaster victim identification and missing persons investigations. As the relevance and value of DNA profiling to forensic investigations has increased, so too has the desire to generate this information from smaller amounts of DNA. Trace DNA samples may be defined as any sample which falls below recommended thresholds at any stage of the analysis, from sample detection through to profile interpretation, and can not be defined by a precise picogram amount. Here we review aspects associated with the collection, DNA extraction, amplification, profiling and interpretation of trace DNA samples. Contamination and transfer issues are also briefly discussed within the context of trace DNA analysis. Whilst several methodological changes have facilitated profiling from trace samples in recent years it is also clear that many opportunities exist for further improvements.
299 citations
Cites background from "Genetics and genomics of core short..."
...The international forensic community identified a small set of core loci mainly consisting of tetranucleotide tandem repeat loci [23,24]....
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TL;DR: A model, "SERV," that predicts the variability of a broad range of tandem repeats in a wide range of organisms and demonstrates significant enrichment of variable repeats within human genes involved in transcriptional regulation, chromatin remodeling, morphogenesis, and neurogenesis.
Abstract: Variable tandem repeats are frequently used for genetic mapping, genotyping, and forensics studies. Moreover, variation in some repeats underlies rapidly evolving traits or certain diseases. However, mutation rates vary greatly from repeat to repeat, and as a consequence, not all tandem repeats are suitable genetic markers or interesting unstable genetic modules. We developed a model, “SERV,” that predicts the variability of a broad range of tandem repeats in a wide range of organisms. The nonlinear model uses three basic characteristics of the repeat (number of repeated units, unit length, and purity) to produce a numeric “VARscore” that correlates with repeat variability. SERV was experimentally validated using a large set of different artificial repeats located in the Saccharomyces cerevisiae URA3 gene. Further in silico analysis shows that SERV outperforms existing models and accurately predicts repeat variability in bacteria and eukaryotes, including plants and humans. Using SERV, we demonstrate significant enrichment of variable repeats within human genes involved in transcriptional regulation, chromatin remodeling, morphogenesis, and neurogenesis. Moreover, SERV allows identification of known and candidate genes involved in repeat-based diseases. In addition, we demonstrate the use of SERV for the selection and comparison of suitable variable repeats for genotyping and forensic purposes. Our analysis indicates that tandem repeats used for genotyping should have a VARscore between 1 and 3. SERV is publicly available from http://hulsweb1.cgr.harvard.edu/SERV/.
210 citations
Additional excerpts
...We also determined the VARscores of some of the most frequently used tandem repeat markers for human forensics (Butler 2006) (Supplemental Table S2)....
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References
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
22,269 citations
TL;DR: The current human genome sequence (Build 35) as discussed by the authors contains 2.85 billion nucleotides interrupted by only 341 gaps and is accurate to an error rate of approximately 1 event per 100,000 bases.
Abstract: The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers approximately 99% of the euchromatic genome and is accurate to an error rate of approximately 1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human genome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead.
3,989 citations
TL;DR: Few genetic markers, if any, have found such widespread use as microsatellites, or simple/short tandem repeats, but features such as hypervariability and ubiquitous occurrence explain their usefulness, but these features also pose several questions.
Abstract: Few genetic markers, if any, have found such widespread use as microsatellites, or simple/short tandem repeats. Features such as hypervariability and ubiquitous occurrence explain their usefulness, but these features also pose several questions. For example, why are microsatellites so abundant, why are they so polymorphic and by what mechanism do they mutate? Most importantly, what governs the intricate balance between the frequent genesis and expansion of simple repetitive arrays, and the fact that microsatellite repeats rarely reach appreciable lengths? In other words, how do microsatellites evolve?
2,140 citations
"Genetics and genomics of core short..." refers background in this paper
...characterized in the human genome (119) and there may be more than a million STR loci present depending on how they are counted (120)....
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TL;DR: The results suggest that trimeric and tetrameric STR loci are useful markers for the study of new mutations and genetic linkage analysis and for application to personal identification in the medical and forensic sciences.
1,474 citations
"Genetics and genomics of core short..." refers background or methods in this paper
...866 Mb D5S818 (54700) AC008512 (11) 5q23....
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...(11) is a CAG repeat located in a coding region (androgen receptor gene, exon 1) that has been directly linked to several genetic diseases (see (88))....
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...3 afibrinogen, 3rd intron Chr 4 156.086 Mb Chr 4 155.866 Mb D5S818 (54700) AC008512 (11) 5q23....
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...175 Mb D16S539 (45590) AC024591 (11) 16q24....
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...STR markers were first described as effective tools for human identity testing in the early 1990s (10,11)....
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Journal Article•
TL;DR: A method enabling rapid localization of STRs and determination of their flanking DNA sequences was developed, thus simplifying the identification of polymorphic STR loci.
Abstract: Tandemly reiterated sequences represent a rich source of highly polymorphic markers for genetic linkage, mapping, and personal identification. Human trimeric and tetrameric short tandem repeats (STRs) were studied for informativeness, frequency, distribution, and suitability for DNA typing and genetic mapping. The STRs were highly polymorphic and inherited stably. A STR-based multiplex PCR for personal identification is described. It features fluorescent detection of amplified products on sequencing gels, specific allele identification, simultaneous detection of independent loci, and internal size standards. Variation in allele frequencies were explored for four U.S. populations. The three STR loci (chromosomes 4, 11, and X) used in the fluorescent multiplex PCR have a combined average individualization potential of 1/500 individuals. STR loci appear common, being found every 300-500 kb on the X chromosome. The combined frequency of polymorphic trimeric and tetrameric STRs could be as high as 1 locus/20 kb. The markers should be useful for genetic mapping, as they are sequence based, and can be multiplexed with the PCR. A method enabling rapid localization of STRs and determination of their flanking DNA sequences was developed, thus simplifying the identification of polymorphic STR loci. The ease by which STRs may be identified, as well as their genetic and physical mapping utility, give them the properties of useful sequence tagged sites (STSs) for the human genome initiative.
1,196 citations
"Genetics and genomics of core short..." refers methods in this paper
...While early work with STRs involved detection on silver-stained polyacrylamide gels (17), the community has embraced fluorescence detection methods involving first gel electrophoresis (10,12,13) and then capillary electrophoresis with such...
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...STR markers were first described as effective tools for human identity testing in the early 1990s (10,11)....
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