The polymorphisms of DYS388 and DYS392 on the Y chromosome in Japanese and German populations

The analysis of a genotype survey in Japanese and German populations at the loci DYS388 and DYS392 located on the Y chromosome is reported. The gene diversities of DYS388 were 0.34 and 0.30 in the Japanese and German males, respectively, and six alleles were found in both groups. The gene diversities of DYS392 were 0.65 and 0.64 and the number of alleles was 8 and 9, respectively in the two populations. The distribution of DYS388 alleles in the Japanese population was different from the German population. The allele distribution of DYS392 showed significant differences among Asian populations. Received: 5 January 1998 / Received in revised form: 27 April 1998     

上海地区汉族健康人群血小板活化因子乙酰水解酶基因7号外显子593位点T/C单核苷酸多态性的研究

目的了解血小板活化因子乙酰水解酶(PAF-AH)基因7号外显子593位点T/C位点单核苷酸多态性(SNP)在中国上海地区汉族健康人群中的分布特征。方法采用聚合酶链反应(PCR)和测序法,对110名上海地区汉族健康者PAF-AH 7号外显子593位点T/C位点的SNP进行检测,计算其基因型和等位基因频率,并结合文献对不同种族该位点的突变情况进行比较。结果对110名上海地区汉族健康者PAF-AH Ile198-Thr(exon7;position 593;T-C)位点多态性进行检测,其PCR扩增产物为240bp。110人中,TT型97人(88.18%),TC型13人(11.82%),未发现CC型。该位点突变的等位基因频率分布也以T(94.09%)最为多见,其次为C(5.91%)。结合文献进行分析发现,上海地区汉族健康人群该位点突变基因型(TC)频率(11.82%)高于德国地区人群(0.95%,P<0.05),但与英国地区人群(7.67%)相比无统计学差异。结论上海地区汉族健康人群PAF-AH第7外显子593位点存在单核苷酸多态性,其T→C位点碱基突变比例较高,该位点突变基因型频率为11.82%,其SNP高于德国地区人群,但与英国地区人群相比无统计学差异。     

A 21 marker insertion deletion polymorphism panel to study biogeographic ancestry

Insertion/deletion polymorphisms have recently received increased interest in the forensic genetics community. This class of markers combines the advantageous genetic properties of single nucleotide polymorphisms (i.e., low mutation rate, genetic stability, and short amplicon size) with the technical advantage of short tandem repeat markers (simple detection by fluorescence-labelled PCR and capillary electrophoresis). For a large number of indel markers significant differences in allele frequencies between the major populations have been reported, making this class of markers suitable for the analysis of biogeographic ancestry. We have developed a multiplex PCR assay designed to establish the biogeographic ancestry of forensic DNA samples based on insertion/deletion polymorphisms. A panel of 21 short indels with allele frequency differences between three major population groups (European, African and Asian) was selected to be incorporated into a single-tube multiplex PCR assay. The assay is highly sensitive, requiring less than 0.5 ng of genomic DNA for successful typing. Due to the short fragment lengths below 200 bp, the assay is ideally suited for the typing of challenging forensic genetic case work samples. A population genetic study has been performed proving the performance of the assay in inferring the ancestral population of individuals. The chosen 21 markers are sufficient to distinguish between three major global population groups. Furthermore, the assay design leaves room for an extension in order to cover additional population groups.     

A novel dimorphism in the human SRY gene: usefulness in human migration studies

A nucleotide polymorphism of C or T was detected at position 465 in the sex-determining region Y (SRY) gene. To evaluate the utility of this dimorphism in human population studies, the frequency and the frequency of the haplotype combined with the two polymorphic loci YAP and M9 were examined in a total of 130 unrelated Japanese and 130 unrelated German males. The T nucleotide was found in 24.6% (32/130) of the Japanese but not in any of the 130 German males. Accordingly, four of the eight possible combination haplotypes of SRY/YAP/M9 were identified in the Japanese population, but one of the four haplotypes comprising SRY(T) was absent in the German samples. This suggests that the C to T transition may be more recent than the YAP insertion or the M9 transversion and the change might have occurred in an ancestral Asian population. These results imply that the dimorphism at the SRY gene is one of the Y-linked markers useful for human population studies and also for ethnic identification of forensic samples. Received: 9 March 1999 / Accepted: 9 September 1999     

HumFES/FPS and HumF13B: Turkish and German population data

The allele distribution of two STRs has been investigated in two populations, i. e. Turks (n = 203/200) and Germans (n = 414/402). The Turkish population showed 11 alleles in HumFES/FPS and 6 alleles in HumF13B while the German population had 9 (FES) and 8 (F13B) alleles respectively. Although the frequency profiles looked quite similiar in both populations, there exist significant differences mainly due to alleles 8 and 10 (F13B) and allele 12 (FES). Four variant alleles have been sequenced and are described. Investigation of 368 (FES)/372 (F13B) meioses revealed no new mutations.     

中国汉族人群SCN5A基因H558R、P1090L、4299+53T＞C及D1819D的多态性研究

目的了解中国汉族人群SCN5A基因单核苷酸多态性少见等位基因频率分布情况。方法在社区体检人群中选择126例作为研究对象,采用限制性片段长度多态性分析（RFLP）对SCN5A基因的H558R、P1090L、4299＋53T〉C及CA457T（D1819D）多态位点进行基因型鉴定,并随机选取样本采用ABI3700毛细血管电泳进行序列测定验证酶切结果。结果SCN5A H558R、P1090L、4299＋53T〉C及C5457T（D1819D）在中国汉族人群中的少见等位基因频率分别为11．1％、5．2％、28．2％及31．8％,与日本及国人先前的研究结果不尽相同。结论SCN5A基因的单核苷酸多态性存在种族差异。     

Eurasiaplex-2: Shifting the focus to SNPs with high population specificity increases the power of forensic ancestry marker sets

To compile a new South Asian-informative panel of forensic ancestry SNPs, we changed the strategy for selecting the most powerful markers for this purpose by targeting polymorphisms with near absolute specificity – when the South Asian-informative allele identified is absent from all other populations or present at frequencies below 0.001 (one in a thousand). More than 120 candidate SNPs were identified from 1000 Genomes datasets satisfying an allele frequency screen of ≥ 0.1 (10 % or more) allele frequency in South Asians, and ≤ 0.001 (0.1 % or less) in African, East Asian, and European populations. From the candidate pool of markers, a final panel of 36 SNPs, widely distributed across most autosomes, were selected that had allele frequencies in the five 1000 Genomes South Asian populations ranging from 0.4 to 0.15. Slightly lower average allele frequencies, but consistent patterns of informativeness were observed in gnomAD South Asian datasets used to validate the 1000 Genomes variant annotations. We named the panel of 36 South Asian-specific SNPs Eurasiaplex-2, and the informativeness of the panel was evaluated by compiling worldwide population data from 4097 samples in four genome variation databases that largely complement the global sampling of 1000 Genomes. Consistent patterns of allele frequency distribution, which were specific to South Asia, were observed in all populations in, or closely sited to, the Indian sub-continent. Pakistani populations from the HGDP-CEPH panel had markedly lower allele frequencies, highlighting the need to develop a statistical system to evaluate the ancestry inference value of counting the number of population-specific alleles present in an individual.     

Tai-Kadai-speaking Gelao population: Forensic features,genetic diversity and population structure

Genetic analyses of geographically and ethno-linguistically different populations are essential for understanding population stratification and genomic structure in medical Genome-Wide Association Studies (GWAS) and genetic variation and diversity related to forensic and population genetics studies. Here, we genotyped 30 autosomal insertion/deletion (Indel) markers from 502 Tai-Kadai-speaking Gelao individuals residing in the rugged topographical area in Southeastern China. In addition, two comprehensive population genetic comparisons of 15,327 individuals from 95 worldwide populations and of 6122 individuals from Asia and adjoining populations were conducted based on allele frequency data and raw genotype data, respectively. All studied markers were found to be in Hardy-Weinberg equilibrium. The combined power of discrimination in the Gelao minority group was 0.999999999975, and the combined probability of exclusion was 0.9879. Our results from the forensic statistical parameters indicated that this Indel panel can be independently used as a powerful tool in forensic individual identification but can only be used as a complementary tool in paternity cases involving East Asians. We also found significant allele frequency differences between the Gelao and other continental populations with respect to the markers grouped in clusters ∼Ⅳ, suggesting that these can be used as forensic ancestry informative Indel markers to distinguish the Gelao from other continental populations. Genetic ancestry analyses demonstrated that Tai-Kadai-speaking Gelao share a dominant ancestry component with Hmong-Mien-speaking Miao. Our population genetic results from multidimensional scaling plots, principal component analysis, neighboring-joining tree construction and hierarchical clustering also suggested that the Zunyi Gelao are genetically closer to their linguistically or geographically close populations, such as the Han Chinese, Guizhou Bouyei and the Hubei Tujia, than to Turkic and Tibeto-Burman speakers.     

Forensic performance of 30 InDels included in the Investigator DIPplex system in Miao population and comprehensive genetic relationship in China

Binary markers of insertion and deletion (InDel) play an important role in forensic personal identification, parentage testing, and individual ancestry inference. We first genotyped 30 InDels included in the Investigator DIPplex in 403 unrelated healthy Zunyi Miao people and analyzed the genetic polymorphisms, as well as explored the genetic relationship between Miao and 32 Chinese reference populations. No departures from the HWE were observed. The combined power of discrimination and the combined probability of exclusion were 0.99999999998 and 0.9884, respectively. Forensic parameters demonstrated that 30 markers are polymorphic and informative in the Zunyi Miao population and can be used as a tool for forensic personal identification and parentage testing. Allele frequency divergence analysis found that 12 out of 30 displaying high allele frequency difference between Turkic-speaking populations and other Chinese populations can be used as candidates of ancestry informative markers for ancestry inference of sub-population in East Asia. Population genetic parameters in the comprehensive population comparison among 33 Chinese populations indicated that our studied Hmong-Mien-speaking Miao has a close genetic relationship with geographically adjacent Enshi Tujia and genetically differentiate from Turkic-speaking populations.

     

Frequencies of D19S433 silent alleles in a Japanese population of 1501 individuals and their effect on likelihood ratios calculated in kinship tests

Although silent alleles in D19S433 typing using the GlobalFiler PCR Amplification Kit have been reported, the exact frequency of the D19S433 silent alleles in population data of 1501 Japanese individuals, which are widely used for the assessment of Japanese STR typing results, is unclear. In this study, we examined the exact D19S433 silent allele frequency in this population data. We newly observed the G32A variant causing silent alleles at D19S433 in five samples. Combining them with data including 30 samples with the variant reported previously, we determined that the total frequency of the silent alleles (i.e. the frequency of the G32A variant) in the 1501 Japanese samples was 0.0117 (35/3002). Using the D19S433 allele frequency data, we evaluated the effect of presence/absence information for the D19S433 silent allele on kinship tests. Likelihood ratios (LRs) were calculated for both simulated parent–child and full sibling cases, revealing that the LR may change by approximately 10⁻² to 10³ fold when the presence/absence of the D19S433 silent allele is revealed in a kinship test. Therefore, if a sufficiently large or small LR is obtained, there is little need to determine the presence/absence of the D19S433 silent allele in Japanese kinship tests using GlobalFiler. This study will be beneficial for the assessment of Japanese human identification and kinship test results using GlobalFiler.     

DXS10011: a hypervariable tetranucleotide STR polymorphism on the X chromosome

The locus DXS10011 is a polymorphic system with a tetranucleotide repeat sequence located on the human X chromosome. The distribution of allele frequencies was examined in 334 Japanese and 171 German individuals and a total of 36 alleles was detected in the two population groups. This STR polymorphism will be a useful marker for linkage analysis. Received: 8 March 1999 / Received in revised form: 14 July 1999     

Relationship between the 1359 G/A polymorphism of the Central Cannabinoid Receptor 1 (CNR1) gene and susceptibility to cannabis addiction in a Turkish population

In this study, we investigate the existence of a possible genetic association between 1359 G/A polymorphism of the Central Cannabinoid Receptor 1 (CNR1) Gene CNR1 (p.Thr453Thr; rs1049353) single nucleotide polymorphism (SNP) and cannabis addiction. DNA samples used in this work are purified from venous leukocytes of 145 unrelated Turkish cannabis-dependent subjects and 140 Turkish control subjects. No significant difference is observed in genotype or allele frequencies of CNR1 1359 G/A polymorphism between these two groups. We also compared CNR1 1359 G/A polymorphism allele frequency distribution in our healthy Turkish population with other healthy populations. The comparison of healthy Turkish subjects with the healthy subjects from English-Irish, Chinese, European-American, African-American, Italian, German and Japanese populations revealed significant differences in allele frequencies. Data indicate that the 1359 G/A CNR1 polymorphism does not contribute to susceptibility to cannabinoid addiction in Turkish subjects. To the best of our knowledge, this is the first study on 1359 G/A CNR1 polymorphism in the Turkish population.     

A novel 56-bp variable tandem repeat polymorphism in the human deoxyribonuclease I gene and its population data

This study confirms the presence of a novel variable number of tandem repeats polymorphism, designated as HumDN1, in intron 4 of the human deoxyribonuclease I (DNase I) gene. Genotyping was performed without difficulty by PCR-amplification and separation by agarose gel electrophoresis in 423 Japanese, originating from four geographically diverse areas in Japan, and 89 Germans. The HumDN1 allele variability was due to different numbers of 56-bp repeat sequences, and five different alleles were distinguished with apparent size between 364 and 588 bp. Although there was a general uniformity for the polymorphism in the Japanese population, significant differences in genotype distribution were found between the Japanese and German populations. Furthermore, linkage disequilibrium between the HumDN1 and DNase I protein polymorphisms was revealed.     

Development and validation of the EUROFORGEN NAME (North African and Middle Eastern) ancestry panel

Inference of biogeographic origin is an important factor in clinical, population and forensic genetics. The information provided by AIMs (Ancestry Informative Markers) can allow the differentiation of major continental population groups, and several AIM panels have been developed for this purpose. However, from these major population groups, Eurasia covers a wide area between two continents that is difficult to differentiate genetically. These populations display a gradual genetic cline from West Europe to South Asia in terms of allele frequency distribution. Although differences have been reported between Europe and South Asia, Middle East populations continue to be a target of further investigations due to the lack of genetic variability, therefore hampering their genetic differentiation from neighboring populations. In the present study, a custom-built ancestry panel was developed to analyze North African and Middle Eastern populations, designated the ‘NAME’ panel. The NAME panel contains 111 SNPs that have patterns of allele frequency differentiation that can distinguish individuals originating in North Africa and the Middle East when combined with a previous set of 126 Global AIM-SNPs.     

Completion of a worldwide reference panel of samples for an ancestry informative Indel assay

The use of ancestry informative markers (AIMs) in forensic analysis is of considerable utility since ancestry inference can progress an investigation when no identification has been made of DNA from the crime-scene. Short-amplicon markers, including insertion deletion polymorphisms, are particularly useful in forensic analysis due to their mutational stability, capacity to amplify degraded samples and straightforward amplification technique. In this study we report the completion of H952 HGDP–CEPH panel genotyping with a set of 46 AIM-Indels. The study adds Central South Asian and Middle Eastern population data, allowing a comparison of patterns of variation in Eurasia for these markers, in order to enhance their use in forensic analyses, particularly when combined with sets of ancestry informative SNPs. Ancestry analysis using principal component analysis and Bayesian methods indicates that a proportion of classification error occurs with European–Middle East population comparisons, but the 46 AIM-Indels have the capability to differentiate six major population groups when European–Central South Asian comparisons are made. These findings have relevance for forensic ancestry analyses in countries where South Asians form much of the demographic profile, including the UK, USA and South Africa. A novel third allele detected in MID-548 was characterized – despite a low frequency in the HGDP–CEPH panel samples, it appears confined to Central South Asian populations, increasing the ability to differentiate this population group. The H952 data set was implemented in a new open access SPSmart frequency browser – forInDel: Forensic Indel browser.     

Increasing the reference populations for the 55 AISNP panel: the need and benefits

Ancestry inference for an individual can only be as good as the reference populations with allele frequency data on the SNPs being used. If the most relevant ancestral population(s) does not have data available for the SNPs studied, then analyses based on DNA evidence may indicate a quite distantly related population, albeit one among the more closely related of the existing reference populations. We have added reference population allele frequencies for 14 additional population samples (with >1100 individuals studied) to the 125 population samples previously published for the Kidd Lab 55 AISNP panel. Allele frequencies are now publicly available for all 55 SNPs in ALFRED and FROG-kb for a total of 139 population samples. This Kidd Lab panel of 55 ancestry informative SNPs has been incorporated in commercial kits by both ThermoFisher Scientific and Illumina for massively parallel sequencing. Researchers employing those kits will find the enhanced set of reference populations useful.

     

Allele frequencies of a SNP and a 27-bp deletion that are the determinant of earwax type in the ABCC11 gene

Allele frequencies for a SNP (rs17822931) and a 27-bp deletion that are the determinant of earwax type in the ABCC11 gene were investigated in seven Japanese, one Korean, and one German populations. The SNP will be useful as one of ancestry information markers, because it showed marked difference in frequencies between Asian and European populations.     

Comparative study on the chronology of third molar mineralization in a Japanese and a German population

In Germany, a sharp increase in forensic age estimations of living persons has been observed in recent years. German law defines four legally relevant age limits: 14, 16, 18 and 21 years. In these age groups, radiographic assessment of the mineralization status of third molars is of particular importance. So far, the influence of ethnicity on the mineralization rate has been insufficiently analyzed. A total of 3031 orthopantomograms of 1597 Japanese and 1434 Germans aged between 12 and 26 years were examined. The mineralization status of third molars was evaluated on the basis of the classification proposed by Demirjian. For the individual mineralization stages, the study presents the mean values and standard deviations (SD) separately for both populations and sexes. The majority of probands from both the Japanese and the German population achieved the C stage and the late G and H stages of third molar development at similar ages. Significant differences between Japanese and Germans were observed, however, with regard to the D, E and F stages defined by Demirjian. Japanese men and women achieved the D, E and F stages approximately 2-3 years later than German men and women. In addition to forensic age determination in living persons, the presented reference data can also be used for age estimations of unidentified deceased persons and skeletons.     

Indel markers: genetic diversity of 38 polymorphisms in Brazilian populations and application in a paternity investigation with post mortem material

Aiming to evaluate the usefulness of 38 non-coding bi-allelic autosomal indels in genetic identification and kinship testing, three Brazilian population samples were studied: two from Rio de Janeiro (including a sample of individuals with self-declared African ancestry) and one Native American population of Terena from Mato Grosso do Sul. Based on the observed allele frequencies, parameters of forensic relevance were calculated. The combined power of discrimination of the 38 indels was high in all studied groups (PD≥0.9999999999997), although slightly lower in Native Americans. Genetic distance analysis showed significant differences between the allele frequencies in the Rio de Janeiro population and those previously reported for Europeans, Africans and Asians explained by its intermediate position between Europeans and Africans. As expected, the Terena sample was significantly different from all the other populations: Brazilians from Rio de Janeiro general population and with self-declared African ancestry, Europeans, Africans and East Asians. Finally, the performance of the 38-indel multiplex assay was tested in post-mortem material with positive results, supporting the use of short amplicon bi-allelic markers as an additional tool to STR analysis when DNA molecules are degraded.     

Identification of a rare off-ladder allele of the D13S325 locus during paternity testing

This study demonstrates an unusual rare allele of D13S325 that was falsely categorized as an allele of D12S391 under the STRtyper™-10F/G system. The parentage cases with these rare alleles were analyzed using the Sinofiler™ system and singleplex amplification system, and the alleles of D13S325 extracted from the electrophoresis gel were sequenced. 5 Cases with the rare alleles misread as allele 20 of D12S391 were identified in total 2618 cases (including 3200 unrelated parents). This rare allele was designated as allele 5.1 of D13S325 based on its DNA sequence. Its frequency in the Chinese population was 1.6 × 10⁻³. Because the rare allele 5.1 of D13S325 locus tends to be incorrectly labeled in the STRtyper™-10F/G system, particular attention should be paid when the system is used in paternity testing, personal identification, and DNA database comparisons.