Analysis of 26 STR loci (PowerPlex® Fusion 6C System) in a mestizo population from Mexico city.

BACKGROUND: Short tandem repeats (STRs) are the most widely used genetic markers in forensic genetics. Therefore, it is essential to document genetic population data of new kits designed for human identification purposes to enable laboratories to use these genetic systems to interpret and solve forensic casework. However, in Mexico, there are no studies with the PowerPlex Fusion 6C System, which includes 26 STRs (23 autosomal STRs and 3 Y-STRs). METHODS AND RESULTS: 600 DNA samples from Mexico City were subjected to genotyping using the PowerPlex Fusion 6C System. For autosomal STRs, 312 different alleles were observed. Combined PE and PD were 99.999999809866% and 99.99999999999999999999999818795%, respectively. Genetic distances and AMOVA test showed low but significant differentiation between Mexican populations. CONCLUSIONS: The results reported in this work demonstrate the efficacy of this system for human identification purposes in the population studied and justify its possible application in other Mexican Mestizo populations.

Population expansion, larger, and more homogeneous native American ancestry among Mexican mestizo populations based on 10 X-chromosome STR loci (X-STR decaplex system).

OBJECTIVE: To evaluate the genetic diversity, admixture, genetic relationships, and sex-biased demographic processes in Mexican Mestizo (admixed) populations based on 10 X-chromosome STRs (X-STRs). METHODS: We analyzed the X-STRs Decaplex system in 104 Mexican Native Americans to obtain the ancestral reference needed to complete the demographic analyses above mentioned. We included reported Iberian and Latin American (admixed) populations from Central and South America, as well as datasets from Mexican Mestizos based on Y-linked STRs (Y-STRs), autosomal STRs (A-STRs), and mtDNA. RESULTS: Higher X-linked Native American ancestry was observed among Latin American populations regarding that reported from A-STRs and Y-STRs. The interpopulation differentiation based on ancestry among Mexican Mestizos diminished according to the inheritance pattern: Y-STRs (highest), A-STRs, X-STRs, and mtDNA (lowest). This finding is related to the peculiar admixture process that occurred during and after the Spanish Conquest of Mexico (and most of Latin America), involving a large number of Spanish men (Y-chromosomes) with a lesser proportion of X-chromosomes than autosomes; besides to the limited number of Spanish women (XX) arrived in the Americas in subsequent and shorter periods. Population expansion was detected in Mexican Mestizos from all the country, except those from the southeast region characterized by elevated indigenous ancestry, marginalization, and poorness. CONCLUSIONS: Population growth was detected in most Mexican Mestizos, besides more homogeneous and larger Native American ancestry based on X-linked inheritance than that based on autosomal STRs and Y-STRs.

Loss of the Y Chromosome: A Review of Molecular Mechanisms, Age Inference, and Implications for Men's Health.

Until a few years ago, it was believed that the gradual mosaic loss of the Y chromosome (mLOY) was a normal age-related process. However, it is now known that mLOY is associated with a wide variety of pathologies in men, such as cardiovascular diseases, neurodegenerative disorders, and many types of cancer. Nevertheless, the mechanisms that generate mLOY in men have not been studied so far. This task is of great importance because it will allow focusing on possible methods of prophylaxis or therapy for diseases associated with mLOY. On the other hand, it would allow better understanding of mLOY as a possible marker for inferring the age of male samples in cases of human identification. Due to the above, in this work, a comprehensive review of the literature was conducted, presenting the most relevant information on the possible molecular mechanisms by which mLOY is generated, as well as its implications for men's health and its possible use as a marker to infer age.

Dietary, Cultural, and Pathogens-Related Selective Pressures Shaped Differential Adaptive Evolution among Native Mexican Populations.

Native American genetic ancestry has been remarkably implicated with increased risk of diverse health issues in several Mexican populations, especially in relation to the dramatic changes in environmental, dietary, and cultural settings they have recently undergone. In particular, the effects of these ecological transitions and Westernization of lifestyles have been investigated so far predominantly on Mestizo individuals. Nevertheless, indigenous groups, rather than admixed Mexicans, have plausibly retained the highest proportions of genetic components shaped by natural selection in response to the ancient milieu experienced by Mexican ancestors during their pre-Columbian evolutionary history. These formerly adaptive variants have the potential to represent the genetic determinants of some biological traits that are peculiar to Mexican people, as well as a reservoir of loci with possible biomedical relevance. To test such a hypothesis, we used genome-wide genotype data to infer the unique adaptive evolution of Native Mexican groups selected as reasonable descendants of the main pre-Columbian Mexican civilizations. A combination of haplotype-based and gene-network analyses enabled us to detect genomic signatures ascribable to polygenic adaptive traits plausibly evolved by the main genetic clusters of Mexican indigenous populations to cope with local environmental and/or cultural conditions. Some of these adaptations were found to play a role in modulating the susceptibility/resistance of these groups to certain pathological conditions, thus providing new evidence that diverse selective pressures have contributed to shape the current biological and disease-risk patterns of present-day Native and Mestizo Mexican populations.

Analysis of the TSER and G>C variants in the TYMS gene: a high frequency of low expression genotypes predicted in the Mexican population.

BACKGROUND: In the TYMS gene promoter, there is a repeat polymorphism (TSER) that affects the expression level of the thymidylate synthetase (TS) enzyme involved in the response to some anticancer drugs. The G>C transversion located in the TSER*3R allele decreases the expression level of the TS enzyme avoiding the upstream stimulatory factor (USF-1) binding site. Despite the biomedical impact of the SNP G>C, only TSER has been reported in most worldwide populations. Thus, we studied both TSER and SNP G>C variants in the Mexican population. SUBJECTS AND METHODS: A population sample (n = 156) was genotyped for the TSER and G>C variants by PCR and PCR-RFLPs, respectively, followed by PAGE and silver staining. RESULTS: For TSER, the most frequent allele was 2 R (52.56%), as well as the genotype 2 R/3R (42.3%). Comparison with Latin American, European, and American (USA) populations suggest a heterogeneous worldwide distribution (FST-value = 0.01564; p-value = 0.0000). When the G>C variant was included (2RG, 3RG, and 3RC), a high frequency of low expression genotypes was observed: 2RG/2RG, 2RG/3RC, and 3RC/3RC (84.6%). CONCLUSION: The high frequency of genotypes associated with low TS enzyme expression justifies obtaining the TYMS gene variant profile in Mexican patient's candidates to pharmaceutical treatments like 5'-Fluoracil, methotrexate, and pemetrex.

Characterization of 58 STRs and 94 SNPs with the ForenSeq™ DNA signature prep kit in Mexican-Mestizos from the Monterrey city (Northeast, Mexico).

BACKGROUND: STR allele frequency databases from populations are necessary to take full advantage of the increased power of discrimination offered by massively parallel sequencing (MPS) platforms. MATERIAL AND METHODS: For this reason, we sequenced 58 STRs (aSTRs, X-STRs, and Y-STRs) and 94 identity informative SNPs (iiSNPs) on 105 Mestizo (admixed) individuals from Monterrey City (Northeast, Mexico), with the Primer Set-A of the ForenSeq™ DNA Signature Prep Kit. RESULTS: Most of the STR markers were in Hardy Weinberg equilibrium, with a few exceptions. We found 346 different length-based alleles for these 58 STRs; nevertheless, they became 528 alleles when the sequence was assessed. The combined power of discrimination from autosomal STRs (aSTRs) was -virtually- 100% in both length and sequence-based alleles, while the power of exclusion was 99.9999999976065 and 99.9999999999494%, respectively. Haplotypes based on X-STRs and Y-STRs showed 100% of discriminatory capacity. CONCLUSIONS: These results provide -for the first time- forensic genomic population data from Mexico necessary for interpretation in kinship and criminal analyses.

Use of Investigator 24plex GO! To analyse allele frequencies of 21 autosomal STRs in the population of Veracruz state, Mexico.

BACKGROUND: Mexican population databases for autosomal STRs are scarce, and no previous studies have been performed with the Qiagen Investigator 24plex GO! AIM: To analyse the frequency of 21 autosomal short tandem repeat (STR) loci and forensic parameters in individuals from Veracruz state, Mexico. SUBJECTS AND METHODS: A total of 234 unrelated individuals were analysed with the Investigator 24plex GO! Kit, which includes the following autosomal STRs: TH01, D3S1358, vWA, D21S11, TPOX, D1S1656, D12S391, SE33, D10S1248, D22S1045, D19S433, D8S133879, D2S1338, D2S441, D18S51, FGA, D16S539, CSF1PO, D13S317, D5S818, and D7S820. Allele frequencies, forensic parameters, and relationships with neighbouring Mexican populations were estimated. RESULTS: The STRs analysed were in Hardy-Weinberg Equilibrium (HWE). The combined matching probability and combined PE were 1.5266 E-24 and 0.999999988711, respectively. The D18S51 and SE33 loci presented the highest Ho (0.8974 and 0.8932) and PE (0.7902 and 0.7815), respectively. The highest PIC (0.9337) and PD (0.9894) values corresponded to SE33. Conversely, D22S1045 had the lowest PIC and PE (0.5533 and 0.3546, respectively). A population cluster among southern Mexican populations, which included non-differentiation between Guerrero and Veracruz states was detected. CONCLUSION: The forensic efficacy of the 21 STRs analysed by the Investigator 24plex GO! Kit was evaluated in the Veracruz state. Moreover, new population clusters that have not yet been described and are related to geographic regions were identified, and these are in agreement with previously reported ancestral differences.

Population diversity of three variants of the SLC47A2 gene (MATE2-K transporter) in Mexican Mestizos and Native Americans.

BACKGROUND: MATE2-K is an efflux transporter protein of organic cation expressed mainly in the kidney and encoded by the SLC47A2 gene. Different variants of this gene have shown an impact on the pharmacokinetics of various drugs, including metformin, which represents one of the most widely used drugs in treating type 2 diabetes. The SLC47A2 gene variants have been scarcely studied in Mexican populations, especially in Native American groups. For this reason, we analyzed the distribution of the variants rs12943590, rs35263947, and rs9900497 within the SLC47A2 gene in 173 Native Americans (Tarahumara, Huichol, Maya, Puerépecha) and 182 Mestizos (admixed) individuals from Mexico. METHODS AND RESULTS: Genotypes were determined through TaqMan probes (qPCR). The Hardy-Weinberg agreement was confirmed for all three SLC47A2 gene variants in all the Mexican populations analyzed. When worldwide populations were included for comparison purposes, for alleles and genotypes a relative interpopulation homogeneity was observed for rs35263947 (T allele; range 23.3-51.1%) and rs9900497 (T allele; range 18.6-40.9%). Conversely, heterogeneity was evident for rs12943590 (A allele, range 22.1-59.1%), where the most differentiated population was the Huichol, with high frequencies of the risk genotype associated with decreased response to metformin treatment (A/A = 40.9%). CONCLUSIONS: Although the SLC47A2 gene variants allow predicting favorable response to the metformin treatment in Mexican populations, the probable high frequency of ineffectiveness should be discarded in Huichols.

Genetic diversity, structure, and admixture in Mayans from Guatemala and Mexico based on 15 short tandem repeats.

OBJECTIVE: To analyze the genetic origin, relationships, structure, and admixture in Mayan Native American groups from Guatemala and Mexico based on 15 autosomal short tandem repeats (STRs) loci commonly used in human identification (HID). METHODS: We genotyped 513 unrelated Mayan samples from Guatemala based on 15 STR loci (AmpFlSTR® Identifiler kit). Moreover, we included 4408 genotypes previously reported, as following: Mayas from Guatemala and Mexico (n = 1666) and from Latin American, European, and African (n = 2742) populations. Forensic parameters, genetic distances, admixture, and population structure were assessed. RESULTS: Forensic parameters of the 15 STRs in different Mayan groups from Guatemala were reported. Low (Fst = 0.78%; p = 0.000) and non-significant differentiation (Fst = 1.8%; p = 0.108) were observed in Mayas from Guatemala and Mexico, respectively. The relative homogeneity observed among Mayan groups supported theories of extensive pre-Columbian gene flow and trade throughout the Mayan Empire. The distribution of the three Native American ancestries among these Mayan groups did not support the presumable Guatemalan origin of Tojolabal and Lacandon people (South, Mexico). The nonsignificant differentiation between Ladinos and Mayas suggests a relative panmixia in Guatemala. Mestizos from southeastern Mexico and Guatemala constitute a core of Native American ancestry in Latin America related to the Mayan Empire in Central America. CONCLUSIONS: The higher European admixture and homogeneity in Mexican Mayas of the Yucatan Peninsula suggest more intensive post-Columbian gene flow in this region than in Guatemalan Mayas.

Predicting Pathogenicity of CDH1 Gene Variants in Patients with Early-onset Diffuse Gastric Cancer from Western Mexico.

BACKGROUND: Early-onset diffuse gastric cancer (EODGC) occurs at or before 50 years of age. Pathogenic mutations and germline deletions in the CDH1 gene (E-cadherin) are well-documented genetic factors associated with the causes of EODGC. OBJECTIVE: The objective of the study was to study CDH1 germline variants and their potential functional impact in patients with EODGC in a Mexican population. METHODS: We studied seven EODGC patients from a biomedical research center in western Mexico. Variants were identified by Sanger sequencing and multiplex ligation-dependent probe amplification. The DeepSEA and SNPClinic v.1.0 software and the Ensembl (1000 Genomes Project, 1kGP) and ClinVar databases were used to predict functional single-nucleotide polymorphisms (SNPs). The genetic admixture of the Mexican patients was corroborated by 22 short tandem repeat loci genotyping and structure analysis. RESULTS: We found 12 germline CDH1 variants in all EODGC patients, and all of them are considered as polymorphisms: rs34561447, rs5030625, rs16260, rs1330727101, rs28372783, rs942269593, rs3743674, rs1801552, rs34939176, rs33964119, rs3556654, and rs1801026. The prediction of regulatory SNPs in the promoter suggests a role for a retrovirus in EODGC that induces the transcription of interferon-related genes through toll-like receptor-interferon response factor 3 signaling, as three SNPs in the CDH1 promoter alter three binding sites for this transcription factor. In addition, SNPs rs28372783 and rs1801026 could alter upstream stimulatory factors 1 (USF1)/USF2-mediated telomerase-dependent lymphocyte activation in EODGC. Other interesting result is a CTCF-dependent shorter CDH1 isoform lacking exon 14, probably due to exon-skipping mediated by rs33964119. CONCLUSIONS: Classical pathogenic germline mutations in the CDH1 gene were not found in these 7 EODGC patients. However, the in silico approaches revealed the possible involvement of a retrovirus and a shorter E-cadherin isoform in EODGC. Nevertheless, further in vitro and in vivo assays are needed to confirm these predictions.

Paternal lineages and forensic parameters based on 23 Y-STRs (Powerplex® Y23) in Mestizo males from Mexico City.

We analyzed 307 Mexican-Mestizo (admixed) males from Mexico City with the Powerplex® Y23 system. The complete list of Y-STR haplotypes was uploaded into the YHRD database (accession number YA004275). The discriminatory capacity (98.70 %) and gene diversity (D = 99.99 %) were calculated, improving the haplotype diversity regarding previous studies in Mexico based on 17 Y-STRs and 12 Y-STRs. Haplogroup distribution assignment was inferred by means of two different online-available algorithms. The Native American Q* haplogroup was the most frequent (66.2 %), followed by the European R1b lineage (19.5 %). In addition, eight Eurasian (3.9%) and two African (6.6%) haplogroups were observed in this population sample from Mexico City. Interestingly, AMOVA test showed a low but significant differentiation among Mexican-Mestizos (Fst = 1.52%; p = 0.0000), suggesting that four population clusters allow to explain their genetic structure according to geographic criteria: north, west, center, and south.

A four-step mutation at D22S1045 in one complex paternity case when the brother of the alleged father hypothesis is evaluated.

We report one complex paternity case presenting a presumable paternal four-step STR mutation between the alleged father (AF) and child; the complexity of the case required the AF-brother hypothesis to be discarded without including this DNA sample. A total of 23 autosomal STR loci included in the Powerplex Fusion® and Globalfiler™ kits confirmed one isolated mismatch for D22S1045 between the AF (17/17) and the male child (13/15) in the presence of the mother (15/15). In this case, the STR structure and father's age do not seem to have contributed to promote the observed multistep mutation. The Paternity Index (PI) based on 23 autosomal STRs did not favor the AF paternity over the AF-brother hypothesis based on a flat prior (PI = 0.1217; W = 10.85%). For that reason, we included 38 autosomal human identification (HID) insertions-deletions (indels) and 20 retrotransposon insertion polymorphisms (RIPs) contained in the InnoTyper® 21 kit. Although these biallelic markers favored the AF paternity rather than the AF-brother hypothesis (LR = 110.3; W = 99.1%), the global PI based on 81 autosomal markers supported moderately the AF paternity hypothesis (LR = 13.4; W = 93.1%). The application of different mutation models showed a consistent support to the AF paternity hypothesis (PI = 93.1-99.95%), which could be useful for interpretation in these multistep STR mutation cases. In brief, we showed the impact of a four-step mutation at D22S1045 to obtain definitive paternity conclusions, particularly under a complex scenario when the AF-brother hypothesis is assessed. Forensic genomics arises as the next option for similar complex paternity cases.

Correction to: A four-step mutation at D22S1045 in one complex paternity case when the brother of the alleged father hypothesis is evaluated.

This article was published online with an error. Given names and family names of the authors were interchanged. The correct author names are presented above. The original article has been corrected.

Inference of maternal uniparental disomy of the entire chromosome 2 from a paternity test.

Atypical situations arise during the constant resolution of paternity cases, which constitute challenges requiring additional genetic systems and non-standard methods. We report a paternity case presenting three alleged father (AF)-child incompatibilities for the markers TPOX, D2S441, and the indel locus B02 (11/11 vs 8/8; 14/14 vs 10/10; 2/2 vs1/1, respectively). Considering the presence of mutations/null alleles, the residual paternity indexes (PI) obtained with 23 autosomal short tandem repeats (STRs) and 38 indels suggest that the AF is the father (PI = 1.94e+011). Although the presence of few incompatibilities also could imply paternity of the AF brother, this hypothesis was less probable (PI = 3.20e+9) (W = 98.4 vs 1.6%, respectively). The inclusion of 23 Y-STR loci confirmed the paternity relationship in this case (global PI = 6.08e+15). However, the two multistep STRs and one indel incompatibilities allow discarding the mutation possibility. On the other hand, the confirmation of the homozygous STR genotypes with two different human identification kits and the low probability to find three null alleles (3.10e-8) allow rejecting the null allele presence hypothesis. Conversely, the child's homozygous genotype for maternal alleles in four markers located in the p and q arms of the chromosome 2 (TPOX, D2S441, D2S1338, and B02) suggests that maternal uniparental isodisomy better explains the relationship despite the presence of three paternal incompatibilities. In brief, when multiple incompatibilities are observed in paternity testing, the chromosomal location of the excluding loci and the use of additional genetic systems can be crucial to get confident kinship conclusions.

Genetic variability among Mexican Mestizo and Amerindian populations based on three ABCB1 polymorphisms.

The most widely studied polymorphisms of the ABCB1 gene are rs1128503 (c.1236C>T), rs2032582 (c.2677G>T/A), and rs1045642 (c.3435C>T). Although variation in ABCB1 allele frequencies among Mexican Mestizos (admixed) from different regions has been observed, Mexican Amerindians have been poorly studied. We aimed to describe the genetic variability of these three ABCB1 polymorphisms in a total sample of 273 Mexican volunteers that included Mestizos from the state of Yucatán, and Amerindians from seven populations (Tarahumara, Mayo, Huichol, Purépecha, Nahua, Tojolabal, and Maya). Genotypes were determined by means of Taq Man probes (qPCR). Genotype distribution was in Hardy-Weinberg equilibrium for all three ABCB1polymorphisms in the eight Mexican populations analyzed. For c.1236C>T and c.3435C>T, the heterozygous C/T was the most frequent genotype in the majority of the studied Mexican populations (range 30.8-65.4%), while heterozygous G/T was the most common genotype for c.2677G>T/A (range 25.9-51.2%), mainly followed by G/G (range 3.2-47.1%) and T/T (range 7.0-35.5%). 12 haplotypes were estimated from the three ABCB1 polymorphisms analyzed, with TTT the most frequent haplotype (mean, 37.0%). Genetic differentiation was demonstrated among the studied Mexican populations (Fst p value < 0.0001), which could imply a diverse drug response or a risk for adverse drug reactions to ABCB1 substrates. Although differences among Amerindians are probably due to genetic drift effects, for Mestizos this could imply variation in admixture composition. In conclusion, interpopulation variability in the observed frequencies of ABCB1 polymorphisms among Mexican Mestizos and Amerindians allow predicting diverse drug responses to ABCB1 substrates in these populations.

Forensic parameters and admixture in seven geographical regions of the Guerrero state (South, Mexico) based on STRs of the Globalfiler® kit.

BACKGROUND: New commercial STR kits have emerged with greater numbers of markers, which allows for obtaining stronger conclusions in forensic casework, which has been poorly studied in Mexico. AIM: To obtain forensic parameters and to analyse the genetic relationships, structure and admixture in seven geographic regions of Guerrero state (South, Mexico) based on the Globalfiler® kit. SUBJECTS AND METHODS: A total of 245 unrelated Mexican individuals from seven regions of the state of Guerrero were analysed with the Globalfiler® kit. Forensic parameters, pairwise comparisons, genetic distances, structure analysis and admixture levels were estimated. RESULTS: Allele frequencies and forensic parameters of 22 STRs were estimated in this Mexican population sample. The combined power of exclusion and power of discrimination values were > 99.9999% and >99.99999999%, respectively. The Native American, European and African ancestries estimated in the Guerrero state population were 70.9%, 25.9% and 3.2%, respectively. CONCLUSION: Forensic validation of the Globalfiler® kit was performed in the Guerrero state population. The geographic isolation level seems to be the principal factor in defining genetic relationships and admixture among the Guerrero sub-populations. Despite the intrinsic limitations of STRs for admixture analysis, these results are very close to previous values based on AIMs and genome-wide SNPs.

Importance of the geographic barriers to promote gene drift and avoid pre- and post-Columbian gene flow in Mexican native groups: Evidence from forensic STR Loci.

OBJECTIVE: To analyze the origin, structure, relationships, and recent admixture in Mexican Native groups based on 15 STRs commonly used in human identification. METHODS: We analyzed 39 Mexican Native population samples using STR databases based on the AmpFlSTR® Identifiler kit (n = 3,135), including Mexican-Mestizos (admixed), European and African populations, as reference. RESULTS: Based upon effective population size (Ne) differences, Native groups were clustered into three regions: i) Center-Southeast groups, characterized by larger Ne, migration rate (Nm), genetic diversity (He), and relative homogeneity principally in the Yucatan Peninsula; ii) Isolated southern groups from Chiapas and Oaxaca, characterized by lower Ne, Nm, and He (i.e. higher isolation and genetic differentiation); iii) North-Northwest groups, which are similar to the previous group but are characterized by generating the widest gene flow barrier in the Pre-Hispanic Mexican territory, and currently by elevated admixture in some northern Native groups. Despite the relative congruence between genetic relationships with cultural, linguistic, geographic criteria, these factors do not explain the present-day population structure of Native groups, excepting in those linguistically related to the Mayan that show higher homogeneity. The Isolation by distance model was demonstrated at long distances (>1,500 km), whereas geographic isolation stands as a determining factor to avoid both non-indigenous admixture and bottleneck processes. CONCLUSIONS: Different dynamics of gene flow and drift were observed among Mexican Native groups, highlighting the geographic barriers (mountains, canyons and jungle regions) as the main factor differentiating Pre-Hispanic populations, and eventually helping to avoid Post-European contact admixture and population bottleneck. Am J Phys Anthropol 160:298-316, 2016. © 2016 Wiley Periodicals, Inc.

Serum Levels of MicroRNA-206 and Novel Mini-STR Assays for Carrier Detection in Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is an X-linked neuromuscular disorder in which the detection of female carriers is of the utmost importance for genetic counseling. Haplotyping with polymorphic markers and quantitation of creatine kinase levels (CK) allow tracking of the at-risk haplotype and evidence muscle damage, respectively. Such approaches are useful for carrier detection in cases of unknown mutations. The lack of informative markers and the inaccuracy of CK affect carrier detection. Therefore, herein we designed novel mini-STR (Short Tandem Repeats) assays to amplify 10 loci within the DMD gene and estimated allele frequencies and the polymorphism information content among other parameters in 337 unrelated individuals from three Mexican populations. In addition, we tested the utility of the assays for carrier detection in three families. Moreover, given that serum levels of miR-206 discern between DMD patients and controls with a high area under the curve (AUC), the potential applicability for carrier detection was assessed. The serum levels of miR-206 of non-carriers (n = 24) and carriers (n = 23) were compared by relative quantitation using real-time PCR (p < 0.05), which resulted in an AUC = 0.80 in the Receiver Operating Characteristic curve analysis. In conclusion, miR-206 has potential as a "liquid biopsy" for carrier detection and genetic counseling in DMD.

Comparison of mutation profiles in the Duchenne muscular dystrophy gene among populations: implications for potential molecular therapies.

Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162) with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001). To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations.

Forensic evaluation of the AmpFℓSTR Identifiler kit in nine Mexican native populations from the pre-Columbian Mesoamerican region.

Allele frequency distribution and forensic parameters of the AmpFℓSTR Identifiler kit was determined in nine Mexican Amerindian populations based on 1,040 unrelated individuals from the pre-Columbian region known as Mesoamerica. Hardy-Weinberg equilibrium was demonstrated for most of the short tandem repeats (STRs) in all nine populations. The power of discrimination and exclusion were higher than 0.99999 and 0.997942, respectively. In addition, a brief overview of the genetic relatedness and structure (F st = 2.62 %; p = 0.00000) between these populations is presented.