In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.

Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, >99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836–0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father–son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RM Y-STRs in identifying and separating unrelated and related males and provides a reference database.

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The role of the proinflammatory interleukin (IL)-18 in cancer progression remains controversial; we thus examined the hypothesis that impaired antitumor immune response in pancreatic carcinoma patients is related to elevated levels of its natural inhibitor IL-18 binding protein (BP) and/or to alteration in the IL-18 receptor complex expression and function. IL-18 and IL-18 binding protein isoform a (BPa) was assessed in pancreatic carcinoma patients at various disease stages, and after surgery/chemotherapy; free bioactive IL-18 concentrations were calculated. IL-18 receptor complex expression in lymphocyte subsets was analyzed and signaling function was assessed versus healthy donors. Carcinoma cells exhibited below normal IL-18BPa expression and above normal IL-18 expression. Circulating IL-18BPa and IL-18 were above controls. Unexpectedly, free unbound IL-18 serum levels were correlated with disease severity and poor survival. IL-18BPa levels were unchanged by surgery but free IL-18 levels were elevated. Gemcitabine with 5-fluorouracil or oxaliplatin, but not alone, increased IL-18 and free IL-18 levels statistically significantly, without affecting IL-18BPa. Spontaneous/induced IL-18 receptor alpha and receptor beta expression in peripheral blood lymphocyte subsets from patients with advanced disease were near-normal, although CD4+ and CD8+ cells were fewer in percentage, and fully functional in inducing interferon-gamma. IL-18 is proposed as novel adjuvant cancer therapy, but free IL-18 levels are increased in the blood of pancreatic carcinoma patients, despite elevated IL-18BP levels, and are associated with poor survival; this highlights recent experimental insights into the prometastatic and proangiogenic effects of IL-18, and suggests that careful preclinical studies are needed to determine the proper application of IL-18 in cancer therapy.

The distribution of Y-chromosomal single nucleotide polymorphism (SNP) haplogroups and short tandem repeat (STR) haplotypes was determined in a sample of 102 unrelated men of Arab origin from northwestern Algeria (Oran area). A total of nine different haplogroups were identified by a panel of 22 binary markers. The most common haplogroups observed in the Algerian population were E3b2 (45.1%) and J1 (22.5%). Y-STR typing by a 17-loci multiplex system allowed 93 haplotypes to be defined (88 were unique). Striking differences in the allele distribution and gene diversity of Y-STR markers between haplogroups could be found. In particular, intermediate alleles at locus DYS458 specifically characterized the haplotypes of individuals carrying haplogroup J1. All the intermediate alleles shared a common repeat sequence structure, supporting the hypothesis that the variant originated from a single mutational event.