Evaluation of seven X-chromosomal short tandem repeat loci located within the Xq26 region.

In this study a set of 29 X-chromosomal short tandem repeats (STRs) located within the Xq26 region was evaluated. These STRs were found within the 133.14-133.45Mb region around the HPRTB locus. Evaluation of the microsatellites was performed with regard to polymorphism, reliable amplification, and low stutter artefacts. DXS10101, DXS10102, and DXS10103 were identified as those X-STRs with highest diversity; i.e. PIC values of 0.7174-0.8933. The locus DXS10101 was the optimal candidate for the integration in the commercial available test system Mentype Argus X-8 PCR amplification kit.

Population genetic evaluation of eight X-chromosomal short tandem repeat loci using Mentype Argus X-8 PCR amplification kit.

The evaluation of four pairs of X-chromosomal short tandem repeats (STRs), i.e. DXS10135-DXS8378, DXS7132-DXS10074, HPRTB-DXS10101 and DXS7423-DXS10134 was carried out using the Argus X-8 Multiplex amplification kit. These eight STRs are distributed as four closely linked pairs over the entire X-chromosome (ChrX), and for practical reasons they are assigned to four linkage groups 1-4. The genetic distance within the STR pairs is assumed to be <1cM, whereas the pair to pair space is about 50 cM or more. Here, we present single STR allele frequencies, haplotype frequencies of the respective STR pairs and further population genetic parameters of forensic interest. Most data refer to a German population, however small samples from Ghana and Japan were also investigated. Furthermore, sequencing of all STR loci displayed the presence of microvariant alleles and variations in the repeat flanking region. A total of 350 meioses investigated here revealed only one sperm DXS7132 mutation. For analysis of linkages within the STR pairs a study involving 104 female meiosis with respect to recombination events was performed. The STR panel presented here provides a powerful tool for solving complex kinship in the case that X-chromosomal lineages can be taken under investigation.

Evaluation of haplotype discrimination capacity of 35 Y-chromosomal short tandem repeat loci.

The haplotype discrimination capacity of the 9 Y-chromosomal short tandem repeat (Y-STR) loci comprising the so called minimal haplotype together with additional 26 recently described single-copy Y-STRs was evaluated within 391 males from Germany, The Netherlands, and Turkey. The aim of this study was to identify the minimum number of Y-STRs needed in addition to the recommended 9 minimal haplotype loci or the 11 SWGDAM loci for individualizing male lineages. Highest gene diversities were shown for DYS385 loci, DYS449, DYS481, DYS570, DYS447, DYS576, DYS389-II, and DYS390 (D=0.7518-0.8746). The five Y-STRs DYS447, DYS449, DYS481, DYS570, and DYS576 comprised the smallest set of loci in addition to the previously recommended standard Y-STRs leading to the individualization of all males from each single population group. Complete resolution of the pooled population was achieved by the additional genotyping of two further loci, DYS446 or DYS505 and DYF406S1 or DYS522.

Y-chromosomal STR haplotypes in Kalmyk population samples.

Seventeen Y-chromosomal short tandem repeats (STRs), DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, GATA-H4, DYS448, DYS456, DYS458, DYS635 were typed in DNA samples from the Kalmyk population (n=99). The population is characterized by a high proportion of duplicated DYS19 alleles and deletions of the locus DYS448 on the background of the Central Asian haplogroup C*. AMOVA analysis reveals a close vicinity to Mongolian and Kazakh populations and large genetic distance to geographical neighbours from Russia, Ukraine and the Caucasus.

Population study and evaluation of 20 Y-chromosome STR loci in Germans.

The nine European minimal haplotype (EMH) loci, the two SWGDAM loci and five further single-copy Y-chromosomal short tandem repeats (Y-STRs) DYS446, DYS447, DYS448, DYS449, DYS463, and the multicopy loci DYS464 were evaluated in the German population groups Dresden, Hamburg, Rostock, Munich, and the Sorbs who are a Slavic-speaking minority in Lusatia. Highest gene diversities in all populations were shown for DYS464, DYS385, and DYS449 (D=0.8559-0.9486). The haplotype diversity for the European minimal haplotype loci ranged between 0.9852 for Sorbs and 0.9983 for the Hamburg population showing that there is a significant portion of haplotypes which could not be resolved. Advanced typing using DYS446, DYS447, DYS448, DYS449, DYS463, and DYS464 discriminated all non-related individuals of the Dresden, Hamburg, and Rostock populations. Evaluation of the Y-STRs was accomplished by sequence analysis of all allelic fragments of the allelic ladders and microvariant alleles of DYS385 and the determination of the amounts of stutter products of the loci.

Y-chromosomal STR haplotype analysis reveals surname-associated strata in the East-German population.

In human populations, the correct historical interpretation of a genetic structure is often hampered by an almost inherent inability to differentiate between ancient and more recent influences upon extant gene pools. One method to trace recent population movements is the analysis of surnames, which, at least in Central Europe, can be thought of as traits 'linked' to the Y chromosome. Illegitimacy, extramarital birth and changes of surnames may have substantially obscured this linkage. In order to assess the actual extent of correlation between surnames and Y-chromosomal haplotypes in Central Europe, we typed Y-chromosomal short tandem repeat markers in 419 German males from Halle. These individuals were subdivided into three groups according to the origin of their respective surname, namely German (G), Slavic (S) or 'Mixed' (M). The distribution of the haplotypes was compared by Analysis of Molecular Variance. While the M group was indistinguishable from group G (PhiST=-0.0008, P>0.5), a highly significant difference (PhiST=0.0277, P<0.001) was observed between the S group and the combined G+M group. This surprisingly strong differentiation is comparable to that of European populations of much larger geographic and linguistic difference. In view of the major migration from Slavic countries into Germany in the 19th century, it appears likely that the observed concurrence of Slavic surnames and Y chromosomes is of a recent rather than an early origin. Our results suggest that surnames may provide a simple means to stratify, and thereby to render more efficient, Y-chromosomal analyses of Central Europeans that target more ancient events.

DXS10079, DXS10074 and DXS10075 are STRs located within a 280-kb region of Xq12 and provide stable haplotypes useful for complex kinship cases.

The evaluation of the short tandem repeat (STR) markers DXS10079, DXS10074 and DXS10075 was amended to establish a STR cluster spanning a genetic distance<1 cM. These three STRs are located within a 280-kb region at Xq12 and provide stable haplotypes useful for solving complex kinship cases. Theoretically, this cluster could give rise to 2,548 different haplotypes in the German population and the genotyping of 781 men revealed the presence of 172 haplotypes. Since the three STRs were shown to be in strong linkage disequilibrium (LD), haplotype frequencies cannot be computed on the basis of a single locus allele frequency alone but have to be estimated directly. Here, we present data on linkage, haplotype frequencies and LD in a German population. Further clusters from other regions of the X chromosome will be published in the future to cover the chromosome with a well-structured network of highly informative sites.

Biodistribution and catabolism of (18)F-labeled neurotensin(8-13) analogs.

4-([(18)F]fluoro)benzoyl-neurotensin(8-13) ((18)FB-Arg(8)-Arg(9)-Pro(10)-Tyr(11)- Ile(12)-Leu(13)-OH, 1) and two analogs stabilized in one and two positions ((18)FB-Arg(8)psi(CH(2)NH)Arg(9)-Pro(10)-Tyr(11)- Ile(12)-Leu(13)-OH, 2, (18)FB-Arg(8)psi(CH(2)NH)Arg(9)-Pro(10)-Tyr(11)-Tle(12)-Leu(13)-OH, 3) were synthesized in a radiochemical yield of 25-36% and a specific activity of 5-15 GBq/mmol. The peptides were evaluated in vitro and in vivo for their potential to image tumors overexpressing neurotensin receptor 1 (NTR1) by positron emission tomography (PET). All analogs exhibited in vitro binding affinity in the low nanomolar range to NTR1-expressing human tumors, measured by quantitative receptor autoradiography, HT-29 and WiDr cells, and to sections of tumors derived from these cell lines in mice. The radiotracers were internalized in the cells in vitro, and the fluorinated peptides were able to mobilize intracellular Ca(2+) of WiDr cells. In in vivo studies in rats and in mice bearing HT-29 cell tumors, only a moderate uptake of the radioligands into the studied tumors was observed, presumed to be due to degradation in vivo and fast elimination by the kidneys. In comparison with the other analogs, the specific tumor uptake expressed as tumor-to-muscle relation was highest for the radioligand 3. The blood clearance of 3 was reduced by co-injection of peptidase inhibitors. The catabolic pathways of the radiofluorinated peptides were elucidated. The results suggest that the high binding affinity to NTR1 and the stabilization against proteolytic degradation are not yet sufficient for tumor imaging by PET.