Autosomal Short Tandem Repeat Loci Research Articles

Population data from sub-populations of the Northern Territory of Australia for 15 autosomal short tandem repeat (STR) loci

It is a requirement that forensic DNA profiling evidence be accompanied by an estimation of its weight, in order that the court can assign an appropriate probative value to the evidence during legal proceedings. There are various models by which this estimation can be made, but each relies on approximations of the allele frequencies in the relevant population. It is also important to assess relevant population genetic features of the available data. This report provides allele frequencies and estimates of common population genetic parameters for the major sub-populations of the Northern Territory of Australia genotyped at 15 autosomal short tandem repeat (STR) loci.

Multistep microsatellite mutation in the maternally transmitted locus D13S317: a case of maternal allele mismatch in the child

Examination of a case of a paternity dispute with 17 autosomal short tandem repeats (STR) loci revealed a mismatch of the maternally transmitted allele at the locus D13S317 in the questioned child. The composition of the alleles of this locus in the mother, questioned child and suspected father was 8/8, 11/11 and 8/11, respectively. The sequence analysis of the regions flanking the locus D13S317 and peak height measurements of the paternal, maternal and child alleles at this locus excluded the possibility of null allele as a cause of the allelic mismatch inherited by the child. The results suggested expansion of the microsatellite repeat motif, TATC by three repeat units as a probable cause for the allelic mismatch in the child. This is a rare case of maternally transmitted multistep microsatellite mutation reported for the first time for this locus in the forensic DNA analysis. The mutation rate at D13S317 locus in maternal and paternal meiosis was 0.04 and 0.14%, respectively, and overall mutation rate was 0.15%. The probability of maternity and paternity were 0.999999 and 0.999999, respectively, for all the 17 autosomal STR loci analyzed. Furthermore, the sequence of two hypervariable regions of mitochondrial DNA, HV1 and HV2 and the maternal alleles of six X chromosome STR loci in the questioned child matched completely with the mother. These results conclusively proved that the mother and suspected father are the biological parents of the questioned child.

Allele frequencies for 15 autosomal STR loci and admixture estimates in Puerto Rican Americans

Allelic frequencies of 15 short tandem repeats (STR) markers (CSF1PO, FGA, THO1, TPOX, VWA, D3S11358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, D19S433 and D2S1338) were determined using the AmpF ℓ STR ® Identifiler ™ PCR Amplification Kit in Puerto Rican American individuals ( N = 205) from Massachusetts. The FGA, D18S51 and D2S1338 loci had a high power of discrimination (PD) with values of 0.967, 0.965 and 0.961, respectively. Significant deviations from the Hardy–Weinberg (HW) equilibrium were not detected. An important genetic contribution of Caucasian European (76.4%) was detected in Puerto Rican Americans. However, comparative analysis between Puerto Rican American and other neighboring populations from United States mainly with African and Caucasian Americans, revealed significant differences in the distribution of STR markers. Our results are important for future comparative genetic studies of different American ethnic groups, in particular a cultural group called Hispanic-Americans and should be helpful for forensic and paternity testing.

Microsatellite markers for standardized genetic management of captive colonies of rhesus macaques (Macaca mulatta)

To preserve genetic variability and minimize genetic subdivision among captive Macaca mulatta at each of the U.S. National Institutes of Health (NIH)-sponsored regional research colonies, the genetic structure of each colony must be characterized. To compare population genetic and demographic parameters across colonies and generations, one standard panel of highly informative genetic markers is required. We assembled a core marker set of four multiplex polymerase chain reaction (PCR) panels comprising 15 autosomal short tandem repeat (STR) loci with high information content selected from existing panels of well-characterized markers that are currently used for parentage assessment and genetic management of rhesus macaques. We then assessed the effectiveness of these loci for providing high probabilities of individual identification and parentage resolution, and for estimating population genetic parameters that are useful for genetic management.

Population data on the seven short tandem repeat loci D4S2366, D6S474, D14S608, D19S246, D20S480, D21S226 and D22S689 in a German population

Allele frequencies for the autosomal tetranucleotide short tandem repeat loci D4S2366, D6S474, D14S608, D19S246, D20S480, D21S226 and D22S689 were investigated in a sample of 189 unrelated German individuals using a multiplex polymerase chain reaction approach. The loci showed no significant deviations from Hardy-Weinberg equilibrium except for D14S608. All genotyped alleles were cloned and sequenced, and an allelic nomenclature consistent with the ISFH recommendations was defined.

Genotypic Polymorphisms at Seventeen Autosomal Short Tandem Repeat Loci in Four Tribal Populations of Andhra Pradesh, India

Four tribal populations of Andhra Pradesh, South India (1), Chenchu (n=100), Lambadi (n=107), Naikpod Gond (n=104) and Yerukula (n=101) were analyzed for DNA polymorphisms at 15 tetranucleotide and 2 pentanucleotide short tandem repeat (STR) loci in the present study.

Genetic Variation at Nine Short Tandem Repeat Loci Among Islanders of the Eastern Adriatic Coast of Croatia

We have analyzed the extent of genetic variation at nine autosomal short tandem repeat loci (D3S1358, VWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317, D7S820) among six populations from Croatia: five distributed in the islands of the eastern Adriatic coast and one from the mainland. The purpose is to investigate the usefulness of these loci in detecting regional genetic differentiation in the studied populations. Significant heterogeneity among the island and mainland populations is revealed in the distributions of allele frequencies; however, the absolute magnitude of the coefficient of gene differentiation is small but significant. The summary measures of genetic variation, namely, heterozygosity, number of alleles, and allele size variance, do not indicate reduced genetic variation in the island populations compared to the mainland population. In contrast to the two measures of genetic variation, allele size variance and within-locus heterozygosity, the imbalance index (beta) indicates evidence of recent expansion of population sizes in all islands and in the mainland. High mutation rates of the studied loci together with local drift effects are likely explanations for interisland genetic variation and the observed lack of reduced genetic diversity among the island populations.

Theory and methodology for utilizing genes as biomarkers to determine potential biological mixtures

Genetically determined mixture information can be used as a surrogate for physical or behavioral characteristics in epidemiological studies examining research questions related to socially stigmatized behaviors and horizontally transmitted infections. A new measure, the probability of mixture discrimination (PMD), was developed to aid mixture analysis that estimates the ability to differentiate single from multiple genomes in biological mixtures. Four autosomal short tandem repeats (STRs) were identified, genotyped and evaluated in African American, European American, Hispanic, and Chinese individuals to estimate PMD. Theoretical PMD frameworks were also developed for autosomal and sex-linked (X and Y) STR markers in potential male/male, male/female and female/female mixtures. Autosomal STRs genetically determine the presence of multiple genomes in mixture samples of unknown genders with more power than the apparently simpler X and Y chromosome STRs. Evaluation of four autosomal STR loci enables the detection of mixtures of DNA from multiple sources with above 99% probability in all four racial/ethnic populations. The genetic-based approach has applications in epidemiology that provide viable alternatives to survey-based study designs. The analysis of genes as biomarkers can be used as a gold standard for validating measurements from self-reported behaviors that tend to be sensitive or socially stigmatizing, such as those involving sex and drugs.

Differences in allele distribution at 15 STR loci among four Japanese regional populations

We examined allele frequency distributions at 15 autosomal short tandem repeat (STR) loci including 13 Combined DNA Index System (CODIS) core STRs in four regional Japanese populations (Akita, Nagoya, Oita and Okinawa). Those distributions were compared pairwise and statistically among them. We also analyzed the distributions with published data on a Korean population by genetic distance D A to construct a tree based on the neighbor-joining method. Consequently, we obtained one that coincides well with their geographical distributions.

Evaluation of gastrointestinal cancer tissues as a source of genetic information for forensic investigations by using STRs

Malignant tissue samples may sometimes be the only source of biological material for forensic investigations, including identification of individuals or paternity testing. However, in use of such samples, uncertainties due to microsatellite instability (MSI) and loss of heterozygosity (LOH) often associated with neoplasias may be encountered. In this study, we have analysed the applicability of autosomal tetranucleotide short tandem repeat (STR) markers, which are routinely used in forensic analysis, to gain genetic information. MSI and LOH were analysed in 41 surgically removed gastrointestinal cancer specimens and the adjascent non-cancerous tissue marginals. The cancer specimens showed great variability in their genetic phenotypes due to MSI or LOH, with only 32% being microsatellite-stable. Of the 15 autosomal STR loci analysed, only TH01 had no MSI-type alteration in these samples. The loci most frequently affected by MSI were D8S1179, D21S11, D18S51 and D19S433 (MSI in 15–17% of cases). LOH-type alterations were observed at all of the loci, including the amelogenin locus used for sex determination. The highest LOH frequency was found at locus D18S51 (27%). The genetic alterations at the marker loci may indicate false homozygosity or heterozygosity, and false gender may result from erroneous deduction of DNA profiles. Therefore, typing of autosomal STRs from malignant tissues in forensic settings warrants careful interpretation of MSI and LOH results together with microscopic analysis of a tissue specimen. Results by two commercially available and widely used forensic DNA profiling kits used here were comparable.

Features of Evolution and Expansion of Modern Humans, Inferred from Genomewide Microsatellite Markers

We study data on variation in 52 worldwide populations at 377 autosomal short tandem repeat loci, to infer a demographic history of human populations. Variation at di-, tri-, and tetranucleotide repeat loci is distributed differently, although each class of markers exhibits a decrease of within-population genetic variation in the following order: sub-Saharan Africa, Eurasia, East Asia, Oceania, and America. There is a similar decrease in the frequency of private alleles. With multidimensional scaling, populations belonging to the same major geographic region cluster together, and some regions permit a finer resolution of populations. When a stepwise mutation model is used, a population tree based on TD estimates of divergence time suggests that the branches leading to the present sub-Saharan African populations of hunter-gatherers were the first to diverge from a common ancestral population (approximately 71-142 thousand years ago). The branches corresponding to sub-Saharan African farming populations and those that left Africa diverge next, with subsequent splits of branches for Eurasia, Oceania, East Asia, and America. African hunter-gatherer populations and populations of Oceania and America exhibit no statistically significant signature of growth. The features of population subdivision and growth are discussed in the context of the ancient expansion of modern humans.

Molecular Relatedness of The Aboriginal Groups of Andaman and Nicobar Islands with Similar Ethnic Populations

The aboriginal tribal groups living in the Andaman and Nicobar Islands are thought to be the descendants of people who were part of the early human dispersal into the Southeast Asia. However, the origin of the tribes of Andaman, the region from where the aboriginals arrived and the route of their migration are still a matter of great speculation. To explore the origin and affinities of the Andaman Islanders, we studied the polymorphism at fifteen autosomal short tandem repeat (STR) loci, mitochondrial control region sequences and eight Y chromosomal STR loci in 194 blood samples, of which 94 samples were from the Andaman Negritos (24 Great Andamanese and 70 Jarawas) and 100 Nicobarese, a Mongoloid group of Nicobar Island and evaluated their relatedness with similar ethnic groups of India, Southeast Asia and Africa. Our results clearly demonstrate that the aboriginal populations of the Andaman Islands – the Great Andamanese and the Jarawas constitute an independent cluster, separating out from all other populations selected in the study. The Nicobarese show a close affinity with the Mongoloid population of Southeast Asia. The distinct genetic identity of the aboriginal populations of the Andaman Islands and other Asian and African populations deciphered by nuclear and mitochondrial DNA diversity suggest that (i) either the aboriginals of Andaman are one of the surviving descendents of settlers from an early migration out of Africa who remained in isolation in their habitat in Andaman Islands, or (ii) they are the descendents of one of the founder populations of modern humans.

Global genetic variation at nine short tandem repeat loci and implications on forensic genetics

We have studied genetic variation at nine autosomal short tandem repeat loci in 20 globally distributed human populations defined by geographic and ethnic origins, viz., African, Caucasian, Asian, Native American and Oceanic. The purpose of this study is to evaluate the utility and applicability of these nine loci in forensic analysis in worldwide populations. The levels of genetic variation measured by number of alleles, allele size variance and heterozygosity are high in all populations irrespective of their effective sizes. Single- as well as multi-locus genotype frequencies are in conformity with the assumptions of Hardy-Weinberg equilibrium. Further, alleles across the entire set of nine loci are mutually independent in all populations. Gene diversity analysis shows that pooling of population data by major geographic groupings does not introduce substructure effects beyond the levels recommended by the National Research Council, validating the establishment of population databases based on major geographic and ethnic groupings. A network tree based on genetic distances further supports this assertion, in which populations of common ancestry cluster together. With respect to the power of discrimination and exclusion probabilities, even the relatively reduced levels of genetic variation at these nine STR loci in smaller and isolated populations provide an exclusionary power over 99%. However, in paternity testing with unknown genotype of the mother, the power of exclusion could fall below 80% in some isolated populations, and in such cases use of additional loci supplementing the battery of the nine loci is recommended.

Estimating divergence time with the use of microsatellite genetic distances: impacts of population growth and gene flow.

Genetic distances play an important role in estimating divergence time of bifurcated populations. However, they can be greatly affected by demographic processes, such as migration and population dynamics, which complicate their interpretation. For example, the widely used distance for microsatellite loci, (deltamu)2, assumes constant population size, no gene flow, and mutation-drift equilibrium. It is shown here that (deltamu)2 strongly underestimates divergence time if populations are growing and/or connected by gene flow. In recent publications, the average estimate of divergence time between African and non-African populations obtained by using (deltamu)2 is about 34,000 years, although archaeological data show a much earlier presence of modern humans out of Africa. I introduce a different estimator of population separation time based on microsatellite statistics, T(D), that does not assume mutation-drift equilibrium, is independent of population dynamics in the absence of gene flow, and is robust to weak migration flow for growing populations. However, it requires a knowledge of the variance in the number of repeats at the beginning of population separation, V(0). One way to overcome this problem is to find minimal and maximal bounds for the variance and thus obtain the earliest and latest bounds for divergence time (this is not a confidence interval, and it simply reflects an uncertainty about the value of V(0) in an ancestral population). Another way to avoid the uncertainty is to choose from among present populations a reference whose variation is presumably close to what it might have been in an ancestral population. A different approach for using T(D) is to estimate the time difference between adjacent nodes on a phylogenetic population tree. Using data on variation at autosomal short tandem repeat loci with di-, tri-, and tetranucleotide repeats in worldwide populations, T(D) gives an estimate of 57,000 years for the separation of the out-of-Africa branch of modern humans from Africans based on the value of V(0) in the Southern American Indian populations; the earliest bound for this event has been estimated to be about 135,000 years. The data also suggest that the Asian and European populations diverged from each other about 20,000 years, after the occurrence of the out-of-Africa branch.

Genetic structure of north-west Africa revealed by STR analysis.

We have analysed a large set of autosomal short tandem repeat (STR) loci in several Arabic and Berber-speaking groups from north-west Africa (ie Moroccan Arabs, northern-central and southern Moroccan Berbers, Saharawis, and Mozabites). Two levels of analysis have been devised using two sets of 12STR loci, (D3S1358, vWA, FGA, THO1, TPOX, CSF1PO, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820) and 21 (the former set plus D9S926, D11S2010, D13S767, D14S306, D18S848, D2S1328, D4S243, F13A1, and FES/FPS). For each set, data for a number of external reference populations were gathered from the literature. Several methods of analysis based on genetic distances (neighbour-joining trees, principal coordinate analysis, boundary detection), as well as AMOVA, showed that genetic differentiation among NW African populations was very low and devoid of any spatial pattern. When the NW African populations were grouped according to cultural or linguistic differences, the partition was not associated with genetic differentiation. Thus, it is likely that Arabisation was mainly a cultural process. A clear genetic difference was found between NW African populations and Iberians, which underscores the Gilbraltar Straits as a strong barrier to genetic exchange; nonetheless, some degree of gene flow into Southern Iberia may have existed. NW Africans were genetically closer to Iberians and to other Europeans than to African Americans.