Defining management units for cetaceans by combining genetics, morphology, acoustics and satellite tracking

Managing animal units is essential in biological conservation and requires spatial and temporal identification of such units. Since even neighbouring populations often have different conservation status and face different levels of anthropogenic pressure, detailed knowledge of population structure, seasonal range and overlap with animals from neighbouring populations is required to manage each unit separately. Previous studies on genetic structure and morphologic separation suggests three distinct populations of harbour porpoises with limited geographic overlap in the North Sea (NS), the Belt Sea (BS) and the Baltic Proper (BP) region. In this study, we aim to identify a management unit for the BS population of harbour porpoises. We use Argos satellite data and genetics from biopsies of tagged harbour porpoises as well as acoustic data from 40 passive acoustic data loggers to determine management areas with the least overlap between populations and thus the least error when abundance and population status is estimated. Discriminant analysis of the satellite tracking data from the BS and NS populations showed that the best fit of the management unit border during the summer months was an east–west line from Denmark to Sweden at latitude 56.95°N. For the border between BS and BP, satellite tracking data indicate a sharp decline in population density at 13.5°E, with 90% of the locations being west of this line. This was supported by the acoustic data with the average daily detection rate being 27.5 times higher west of 13.5°E as compared to east of 13.5°E. By using this novel multidisciplinary approach, we defined a management unit for the BS harbour porpoise population. We recommend that these boundaries are used for future monitoring efforts of this population under the EU directives. The boundaries may also be used for conservation efforts during the summer months, while seasonal movements of harbour porpoises should be considered during winter

Delineating genotype and parent-of-origin effect on the phenotype in MSH6-associated Lynch syndrome

Background: This study investigates the potential influence of genotype and parent-of-origin effects (POE) on the clinical manifestations of Lynch syndrome (LS) within families carrying (likely) disease-causing MSH6 germline variants. Patients and Methods: A cohort of 1615 MSH6 variant carriers (310 LS families) was analyzed. Participants were categorized based on RNA expression and parental inheritance of the variant. Hazard ratios (HRs) were calculated using weighted Cox regression, considering external information to address ascertainment bias. The findings were cross-validated using the Prospective Lynch Syndrome Database (PLSD) for endometrial cancer (EC). Results: No significant association was observed between genotype and colorectal cancer (CRC) risk (HR = 1.06, 95% confidence interval [CI]: 0.77–1.46). Patients lacking expected RNA expression exhibited a reduced risk of EC (Reference Cohort 1: HR = 0.68, 95% CI: 0.43–1.03; Reference Cohort 2: HR = 0.63, 95% CI: 0.46–0.87). However, these results could not be confirmed in the PLSD. Moreover, no association was found between POE and CRC risk (HR = 0.78, 95% CI: 0.52–1.17) or EC risk (Reference Cohort 1: HR = 0.93, 95% CI: 0.65–1.33; Reference Cohort 2: HR = 0.8, 95% CI: 0.64–1.19). Discussion and Conclusion: No evidence of POE was detected in MSH6 families. While RNA expression may be linked to varying risks of EC, further investigation is required to explore this observation.</p

Delineating genotype and parent-of-origin effect on the phenotype in MSH6-associated Lynch syndrome

Background: This study investigates the potential influence of genotype and parent-of-origin effects (POE) on the clinical manifestations of Lynch syndrome (LS) within families carrying (likely) disease-causing MSH6 germline variants. Patients and Methods: A cohort of 1615 MSH6 variant carriers (310 LS families) was analyzed. Participants were categorized based on RNA expression and parental inheritance of the variant. Hazard ratios (HRs) were calculated using weighted Cox regression, considering external information to address ascertainment bias. The findings were cross-validated using the Prospective Lynch Syndrome Database (PLSD) for endometrial cancer (EC). Results: No significant association was observed between genotype and colorectal cancer (CRC) risk (HR = 1.06, 95% confidence interval [CI]: 0.77–1.46). Patients lacking expected RNA expression exhibited a reduced risk of EC (Reference Cohort 1: HR = 0.68, 95% CI: 0.43–1.03; Reference Cohort 2: HR = 0.63, 95% CI: 0.46–0.87). However, these results could not be confirmed in the PLSD. Moreover, no association was found between POE and CRC risk (HR = 0.78, 95% CI: 0.52–1.17) or EC risk (Reference Cohort 1: HR = 0.93, 95% CI: 0.65–1.33; Reference Cohort 2: HR = 0.8, 95% CI: 0.64–1.19). Discussion and Conclusion: No evidence of POE was detected in MSH6 families. While RNA expression may be linked to varying risks of EC, further investigation is required to explore this observation.</p

SNP association study in PMS2-associated Lynch syndrome

Lynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly on MLH1, MSH2 and MSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs in PMS2 mutation carriers. A cohort study was performed in 507 PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3. Hazard ratios (HRs) were calculated using a weighted Cox regression analysis to correct for ascertainment bias. Discrimination was assessed with a concordance statistic in a bootstrap cross-validation procedure. Individual SNPs only had non-significant associations with CRC occurrence with HRs lower than 2, although male carriers of allele A at rs1321311 (6p21.31) may have increased risk of CRC (HR = 2.1, 95% CI 1.2–3.0). A polygenic risk score (PRS) based on 24 HRs had an HR of 2.6 (95% CI 1.5–4.6) for the highest compared to the lowest quartile, but had no discriminative ability (c statistic 0.52). Previously suggested SNPs do not modify CRC risk in PMS2 carriers. Future large studies are needed for improved risk stratification among Lynch syndrome patients