Development and validation of a new multiplex for upgrading Y-STRs population databases from 12 to 23 markers and its forensic casework application.

Y chromosomal short tandem repeats (Y-STRs) are used in forensic investigations as a useful complementary tool to autosomal markers. The ongoing development of new kits with an increasing number of markers makes it necessary to update populations typed in the Y-STR Haplotype Reference Database to reach at least 23 Y-STRs. A novel Y-STR multiplex panel was developed to offer a cost-efficient alternative to update Y-STR haplotypes from 12 to 23 loci. This panel includes the eleven markers, DYS448, DYS456, DYS458, DYS635, Y-GATA H4, DYS576, DYS481, DYS549, DYS533, DYS570 and DYS643, as well as DYS385a/b for traceability purpose. Developmental validation of this panel was conducted following the recommendations of the Scientific Working Group on DNA Analysis Methods (SWGDAM), showing high sensitivity, tolerance to common inhibitors as well as high species specificity. It was efficient for degraded DNA samples and for detection of male mixtures. When applying it for extending the current data of the Ibiza population, both the discrimination capacity and the haplotype diversity increased from 0.5952 to 0.9048 and from 0.9808 to 0.9977, respectively. Together, the study demonstrates the suitability of this panel in forensic casework.

In silico identification and in vitro expression analysis of breast cancer-related m6A-SNPs.

Research on m6A-associated SNPs (m6A-SNPs) has emerged recently due to their possible critical roles in many key biological processes. In this sense, several investigations have identified m6A-SNPs in different diseases. In order to gain a more complete understanding of the role that m6A-SNPs can play in breast cancer, we performed an in silico analysis to identify the m6A-SNPs associated with breast cancer and to evaluate their possible effects. For this purpose, we downloaded SNPs related to breast cancer and a list of m6A-SNPs from public databases in order to identify which ones appear in both. Subsequently, we assessed the identified m6A-SNPs in silico by expression quantitative trait loci (eQTL) analysis and differential gene expression analysis. We genotyped the m6A-SNPs found in the in silico analysis in 35 patients with breast cancer, and we carried out a gene expression analysis experimentally on those that showed differences. Our results identified 981 m6A-SNPs related to breast cancer. Four m6A-SNPs showed an eQTL effect and only three were in genes that presented an altered gene expression. When the three m6A-SNPs were evaluated in the tissue sample of our breast cancer patients, only the m6A-SNP rs76563149 located in ZNF354A gene presented differences in allele frequencies and a low gene expression in breast cancer tissues, especially in luminal B HER2+ subtype. Future investigations of these m6A-SNPs should expand the study in different ethnic groups and increase the sample sizes to test their association with breast cancer and elucidate their molecular function.

Post-Austronesian migrational wave of West Polynesians to Micronesia.

This study examines Y-chromosome and mtDNA markers in the population of the island of Kiritimati in the context of geographically targeted reference populations from the Pacific. Kiritimati derives its population from the atoll islands of the Gilbert Archipelago and representsa geographicaltransitional region between Micronesia, Polynesia and Melanesia that likely played a critical role during theAustronesian expansion. The large presence(84.1%)of individuals withO-M175, O2a-M324 and O2a2b-P164 sub-haplogroups, 69.9% being O2a2b-P164, the Y-STR homogeneity within O2a2b-P164 and the very recent age of the sub-haplogroup(363-548 years ago)inKiritimati suggestthe arrival ofa genetically homogenous population to the Gilberteses followed by a population expassion.The close Y-STR haplotype affinities with profiles from the Samoa and Tonga Archipelagos point to an unprecedented massive post-Austronesian expansionexodus from West Polynesia.Contrasting the abundance of AustronesianO2a2b-P164 sub-haplogroup, the most abundantMelanesian/Papuansub-haplogroup,C-M130is present at a frequency of 13.5%. Thenetwork topology suggests that C-M130 arrived to theKiribati Archipelago from West Polynesia, specifically from West Samoa, Tonga and/or Tutuila subsequent to the Austronesian expansion about 832-1408 years ago. The haplotype affinities withinO2a2b-P164 argue for anoriginal source in Taiwan and its dispersal to West Polynesia and then to Southeast Micronesia. The present investigation provides an understanding of the genetic composition and complex migration history of an understudied region of the Pacific and provides evidence for recent dispersals towards Micronesia from West Polynesia subsequent to the initial Austronesian expansion.

Association of LCT -13910C>T polymorphism and hip fracture in a cohort of older adult population from Northern Spain.

Hip fracture is a common health problem very frequent in the older adult population and is associated with significant morbidity, mortality, and societal costs. There are several factors that increase the risk of suffering a hip fracture, however, the effect of genetic lactase non-persistence is not clear-cut yet. For this reason, we investigated if the LCT -13910C>T polymorphism is a potential risk factor for osteoporotic hip fractures in older adult people from the Northern Spain population. A total of 740 individuals were included in this study. Of them, 364 belonged to the group of patients whit osteoporotic hip fracture while the control group consisted of 376 individuals without hip fracture. The genotypes for the LCT -13910C>T polymorphism were analyzed by using polymerase chain reaction and high resolution melting. The prevalence of the CC genotype, which is related to lactase non-persistence, did not differ significantly in both groups. Likewise, no differences were observed between groups when they were compared with regard to the C or the T allele, or when they were analyzed considering gender. Additionally, our results were compared with those obtained in a control group of 207 nonagenarian individuals originally from Northern Spain and no differences were observed. In conclusion, no significant association was observed between the LCT -13910C>T polymorphism and the risk for suffering hip fracture in the older adult population of Northern Spain.

Study of 17 X-STRs in Native American and Mestizo populations of Central America for forensic and population purposes.

In the present work, an extensive analysis of the X-chromosomal pool of Native American and Mestizo groups of Central America (Guatemala, El Salvador, Nicaragua, and Panama) has been carried out. Allele and haplotype frequency databases, as well as other forensic parameters for these populations, are presented. The admixture analysis supports the tri-hybrid composition in terms of ancestry in the Mestizo populations, with a predominant Native American contribution (54-69%), followed by European (19-28%) and African contributions (12-19%). Pairwise FST genetic distances highlight the genetic proximity between the northernmost Central American populations, especially among admixed populations. The unique and complex nature of this area, where populations from different origins intercrossed, as well as the informativity of X-STR data, highpoint the great interest of this genetic study. Furthermore, the X-chromosome databases for Central American populations here provided will be not only useful for forensic and population purposes not only in the target countries but also in the host countries.