Influence of model selection and data structure on the estimation of genetic parameters in honeybee populations

Estimating genetic parameters of quantitative traits is a prerequisite for animal breeding. In honeybees, the genetic variance separates into queen and worker effects. However, under data paucity, parameter estimations that account for this peculiarity often yield implausible results. Consequently, simplified models which attribute all genetic contributions to either the queen (queen model) or the workers (worker model) are often used to estimate variance components in honeybees. However, the causes for estimations with the complete model (colony model) to fail and the consequences of simplified models for variance estimates are little understood. We newly developed the necessary theory to compare parameter estimates that were achieved by the colony model with those of the queen and worker models. Furthermore, we performed computer simulations to quantify the influence of model choice, estimation algorithm, true genetic parameters, rates of controlled mating, apiary sizes, and phenotype data completeness on the success of genetic parameter estimations. We found that successful estimations with the colony model were only possible if at least some of the queens mated controlledly on mating stations. In that case, estimates were largely unbiased if more than 20% of the colonies had phenotype records. The simplified queen and worker models proved more stable and yielded plausible parameter estimates for almost all settings. Results obtained from these models were unbiased when mating was uncontrolled, but with controlled mating, the simplified models consistently overestimated heritabilities. This work elucidates the requirements for variance component estimation in honeybees and provides the theoretical groundwork for simplified honeybee models.

A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic influences. There is an increasing demand for ASD genetic testing beyond the traditionally recommended microarray and syndromic autism testing; however, the current whole genome sequencing (WGS) and whole exome sequencing (WES) methods are lacking an academic standard for WGS variant annotation, reporting, and interpretation, tailored towards patients with ASD and offer very limited interpretation for clinical significance. Using WGS data from six family trios, we demonstrate the clinical feasibility and technical implementation of an evidence-based, fully transparent bioinformatics pipeline and report framework for an ASD-focused WGS genetic report. We confirmed a portion of the key variants with Sanger sequencing and provided interpretation with consideration of patients’ clinical symptoms and detailed literature review. Furthermore, we showed that identification of the genetic contributions of ASD core symptoms and comorbidities may promote a better understanding of the ASD pathophysiology, lead to early detection of associated comorbidities, and facilitate pharmacologic intervention based on pathological pathways inferred from the genetic information. We will make the bioinformatics pipeline and interpretation framework publicly available, in an easily accessible format, after validation with a larger cohort. We hope that the present proposed protocol can serve as a starting point to invite discourse and debate to further improve approaches in WGS-based genetic consultation for patients with ASD.

PLUM VARIETIES USED AS PARENTS IN ROMANIAN BREEDING PROGRAM

There are about three thousand varieties belonging to Prunus domestica available at present worldwide that can be used as genitors in plum breeding activity. An analysis of the pedigrees of plum cvs. developed in Romanian breeding programs shows that the most are descended from ‘Tuleu gras’, ‘Renclod Althan’, ‘Anna Späth’, ‘Stanley’ and ‘Early Rivers’, called 'ancestors'. That means the majority of plum cvs. have at least one of the ancestors as parent or grandparent. For those 40 plum cvs. registered in Romania in 60 years an increased number of crosses with these 'ancestors' has led to what we call 'inbreeding'. According to data presented in this paper, ‘Tuleu gras’ cv. was the most frequently used parent in the cross combinations, giving origin to 23 cvs. Among the other frequently used genitors were: ‘Renclod Althan’ (7 cvs.), ‘Anna Späth’ (3 cvs.) and ‘Stanley’ (1 cv.). Many of the cultivars – 32 altogether (80%) have originated from hybridization, whereas 4 cvs. have originated from open pollination, others 3 cvs. from mutagenesis and 1 cv. from clonal selection. The goal of this work is to measure genetic diversity presently use in Romanian plum breeding. Pedigrees of each cv. were used to study the genetic contributions of ancestor. Of the 40 cvs. analyzed, 33 had an inbreeding coefficient other than zero. The overall mean inbreeding coefficient was 0.419 for all cvs., where their parentages were known. For cvs. with unknown parentage (nonrelated with known parentage) the inbreeding coefficient is zero. The mean coefficient of coancestry of 40 plum cvs. are 0.081 with ‘Tuleu gras’ cv., 0.019 with ‘Renclod Althan’ and ‘Anna Späth’ cvs., 0.017 with ‘Early Rivers’ cv., 0.014 with ‘d’Agen’ and ‘Renclod Violet’ cvs. and 0.005 with Stanley cv. In conclusion, plum breeders have worked with populations of greatly reduced genetic diversity and this strategy becomes a problem because it leads to genetic impoverishment, and, also, the loss of the genetic resistance to different diseases.

Host Genetic Liability for Severe COVID-19 Associates with Alcohol Drinking Behavior and Diabetic Outcomes in Participants of European Descent

Risk factors and long-term consequences of COVID-19 infection are unclear but can be investigated with large-scale genomic data. To distinguish correlation from causation, we performed in-silico analyses of three COVID-19 outcomes (N > 1,000,000). We show genetic correlation and putative causality with depressive symptoms, metformin use (genetic causality proportion (gĉp) with severe respiratory COVID-19 = 0.576, p = 1.07 × 10−5 and hospitalized COVID-19 = 0.713, p = 0.003), and alcohol drinking status (gĉp with severe respiratory COVID-19 = 0.633, p = 7.04 × 10−5 and hospitalized COVID-19 = 0.848, p = 4.13 × 10−13). COVID-19 risk loci associated with several hematologic biomarkers. Comprehensive findings inform genetic contributions to COVID-19 epidemiology, molecular mechanisms, and risk factors and potential long-term health effects of severe response to infection.

Micro- and macroevolutionary change of colony-level traits in bryozoans

The evolution of trait variation among populations of animals is difficult to study due to the many overlapping genetic and environmental influences that control phenotypic expression. In a group of animals, bryozoans, it is possible to isolate genetic contributions to phenotypic variation, due to the modular nature of bryozoan colonies. Each bryozoan colony represents a snapshot of the phenotypes that correspond to a single genotype, which can be summarized as a phenotypic distribution. We test whether these phenotypic distributions are heritable across generations of colonies in two sister species of the bryozoan Stylopoma, grown and bred in a common garden breeding experiment. We find that components of phenotypic distributions, specifically median trait values of colony members, are heritable between generations of colonies. Furthermore, this heredity has macroevolutionary importance because it correlates with the morphological distance between these two species. Because parts of phenotypic distributions are heritable, and this heritability corresponds to evolutionary divergence between species, we infer that these distributions have the potential to evolve. The evolutionary potential of these phenotypic distributions may underpin the emergence of colony-level traits, like division of labor in colonies.

Competition alters species’ plastic and genetic response to environmental change

Species react to environmental change via plastic and evolutionary responses. While both of them determine species’ survival, most studies quantify these responses individually. As species occur in communities, competing species may further influence their respective response to environmental change. Yet, how environmental change and competing species combined shape plastic and genetic responses to environmental change remains unclear. Quantifying how competition alters plastic and genetic responses of species to environmental change requires a trait-based, community and evolutionary ecological approach. We exposed unicellular aquatic organisms to long-term selection of increasing salinity—representing a common and relevant environmental change. We assessed plastic and genetic contributions to phenotypic change in biomass, cell shape, and dispersal ability along increasing levels of salinity in the presence and absence of competition. Trait changes in response to salinity were mainly due to mean trait evolution, and differed whether species evolved in the presence or absence of competition. Our results show that species’ evolutionary and plastic responses to environmental change depended both on competition and the magnitude of environmental change, ultimately determining species persistence. Our results suggest that understanding plastic and genetic responses to environmental change within a community will improve predictions of species’ persistence to environmental change.

Twin Similarity for Neighborhood, Geographic Mobility, and Health Outcomes in Late Adulthood

Socioeconomic status (SES) is one of the most robust predictors of health. The source of SES-health associations is heavily debated; one approach is investigating neighborhood-level environmental characteristics. Challenges include selection effects and the possibility of reverse causation: people choose their neighborhoods. Longitudinal twin research can overcome these issues by assessing location choice over time as well as twin similarity; however, few existing twin studies have incorporated neighborhood-level data, and none of those focus on aging. Using longitudinal data from the Swedish Adoption/Twin Study of Aging, the current study examined the impact of location at various points in life. Location at birth and in 1993 were available for 972 participants. Birth years ranged from 1926 to 1948; mean age in 1993 was 54.55 (range = 35-67). Thirty-nine percent of the sample had moved to a different county between birth and midlife: individuals who moved had significantly higher parental SES and had achieved significantly higher education. Moreover, identical twin concordance for geographic mobility (77%) was significantly higher than fraternal twin concordance (65%), indicating a modest but significant genetic contribution. Geographic mobility did not impact identical twin similarity on a functional aging factor (corrected for age and education), but fraternal twins concordant for mobility were more similar than discordant twins, suggesting genetic contributions to mobility may also impact health. Ongoing retrieval of location information for twins born 1900-1925 and geocoding of location information available at 9 waves of data collection will allow for expanded investigation of the SES-health relationship at the neighborhood level.

Genetic Contributions to Prostate Cancer Disparities in Men of West African Descent

Prostate cancer (PCa) is the second most frequently diagnosed malignancy and the second leading cause of death in men worldwide, after adjusting for age. According to the International Agency for Research on Cancer, continents such as North America and Europe report higher incidence of PCa; however, mortality rates are highest among men of African ancestry in the western, southern, and central regions of Africa and the Caribbean. The American Cancer Society reports, African Americans (AAs), in the United States, have a 1.7 increased incidence and 2.4 times higher mortality rate, compared to European American’s (EAs). Hence, early population history in west Africa and the subsequent African Diaspora may play an important role in understanding the global disproportionate burden of PCa shared among Africans and other men of African descent. Nonetheless, disparities involved in diagnosis, treatment, and survival of PCa patients has also been correlated to socioeconomic status, education and access to healthcare. Although recent studies suggest equal PCa treatments yield equal outcomes among patients, data illuminates an unsettling reality of disparities in treatment and care in both, developed and developing countries, especially for men of African descent. Yet, even after adjusting for the effects of the aforementioned factors; racial disparities in mortality rates remain significant. This suggests that molecular and genomic factors may account for much of PCa disparities.