Lipid-Associated Variants near ANGPTL3 and LPL Show Parent-of-Origin Specific Effects on Blood Lipid Levels and Obesity

Parent-of-origin effects (POE) and sex-specific parental effects have been reported for plasma lipid levels, and a strong relationship exists between dyslipidemia and obesity. We aim to explore whether genetic variants previously reported to have an association to lipid traits also show POE on blood lipid levels and obesity. Families from the Botnia cohort and the Hungarian Transdanubian Biobank (HTB) were genotyped for 12 SNPs, parental origin of alleles were inferred, and generalized estimating equations were modeled to assess parental-specific associations with lipid traits and obesity. POE were observed for the variants at the TMEM57, DOCK7/ANGPTL3, LPL, and APOA on lipid traits, the latter replicated in HTB. Sex-specific parental effects were also observed; variants at ANGPTL3/DOCK7 showed POE on lipid traits and obesity in daughters only, while those at LPL and TMEM57 showed POE on lipid traits in sons. Variants at LPL and DOCK7/ANGPTL3 showed POE on obesity-related traits in Botnia and HTB, and POE effects on obesity were seen to a higher degree in daughters. This highlights the need to include analysis of POEs in genetic studies of complex traits.

Transmission distortion and genetic incompatibilities between alleles in a multigenerational mouse advanced intercross line

While direct additive and dominance effects on complex traits have been mapped repeatedly, additional genetic factors contributing to the heterogeneity of complex traits have been scarcely investigated. To assess genetic background effects, we investigated transmission ratio distortions (TRDs) of alleles from parent to offspring using an advanced intercross line (AIL) of an initial cross between the mouse inbred strains C57BL/6NCrl (B6N) and BFMI860-12 (BFMI). 341 males of generation 28 and their respective 61 parents and 66 grandparents were genotyped using Mega Mouse Universal Genotyping Arrays (MegaMUGA). TRDs were investigated using allele transmission asymmetry tests, and pathway overrepresentation analysis was performed. Sequencing data was used to test for overrepresentation of non-synonymous SNPs in TRD regions. Genetic incompatibilities were tested using the Bateson-Dobzhansky-Muller two-locus model. 62 TRD regions were detected, many in close proximity to the telocentric centromere. TRD regions contained 44.5% more non-synonymous SNPs than randomly selected regions (182 vs. 125.9 ± 17.0, P < 1x10−4). Testing for genetic incompatibilities between TRD regions identified 29 genome-wide significant incompatibilities between TRD regions (P(BF) < 0.05). Pathway overrepresentation analysis of genes in TRD regions showed that DNA methylation, epigenetic regulation of RNA, and meiotic/meiosis regulation pathways were affected independent of the parental origin of the TRD. Paternal BFMI TRD regions showed overrepresentation in the small interfering RNA (siRNA) biogenesis and in the metabolism of lipids and lipoproteins. Maternal B6N TRD regions harbored genes involved in meiotic recombination, cell death, and apoptosis pathways. The analysis of genes in TRD regions suggests the potential distortion of protein-protein interactions influencing obesity and diabetic retinopathy as a result of disadvantageous combinations of allelic variants in Aass, Pgx6 and Nme8. Using an AIL significantly improves the resolution at which we can investigate TRD. Our analysis implicates distortion of protein-protein interactions as well as meiotic drive as the underlying mechanisms leading to the observed TRD in our AIL. Furthermore, genes with large amounts of non-synonymous SNPs located in TRD regions are more likely to be involved in pathways that are related to the phenotypic differences between the parental strains. Genes in these TRD regions provide new targets for investigating genetic adaptation, protein-protein interactions, and determinants of complex traits such as obesity.

The Interplay Between the Early Work and Family Trajectories of Young Adult Women Born in West Germany: Differences by Parental Origins

Using data from the German Socio-Economic Panel (GSOEP), this paper employs sequence analysis to identify “typical” early (observation window limited to ages 15 to 30) employment and family formation trajectories among female second-generation migrants in Germany. For the employment domain of the life course, four types of employment trajectories were identified according to their modal states: “long education,” “full-time employment,” “part-time employment,” and “non-employment.” For the family domain of the life course, three types of family trajectories were identified: “postponement of family formation,” “early family formation,” and “early single motherhood.” For the analysis on cluster affiliation, a multinomial logistic regression was used to investigate how parental origin relates to jointly determined employment and family trajectories. As expected, the descriptive results showed that trajectories of low labor market participation are highly related to trajectories of early family formation. The categorization by parental origins shows that there were few differences in the trajectories of most native and G2 women groups. One pattern that stood out was that compared to other origin groups, G2 women of Turkish parental origin were more likely to be on an early family formation path, and they were more likely to be on a path with multiple non-employment spells. In the modeling strategy, the remaining differences in the women’s patterns were partially explained by the differences in their socioeconomic backgrounds (compulsory school track and the father’s professional degree) and their maternal employment role models (the mother’s employment when the woman was age 15).

Molecular Cytogenetics in the Era of Chromosomics and Cytogenomic Approaches

Here the role of molecular cytogenetics in the context of yet available all other cytogenomic approaches is discussed. A short introduction how cytogenetics and molecular cytogenetics were established is followed by technical aspects of fluorescence in situ hybridization (FISH). The latter contains the methodology itself, the types of probe- and target-DNA, as well as probe sets. The main part deals with examples of modern FISH-applications, highlighting unique possibilities of the approach, like the possibility to study individual cells and even individual chromosomes. Different variants of FISH can be used to retrieve information on genomes from (almost) base pair to whole genomic level, as besides only second and third generation sequencing approaches can do. Here especially highlighted variations of FISH are molecular combing, chromosome orientation-FISH (CO-FISH), telomere-FISH, parental origin determination FISH (POD-FISH), FISH to resolve the nuclear architecture, multicolor-FISH (mFISH) approaches, among other applied in chromoanagenesis studies, Comet-FISH, and CRISPR-mediated FISH-applications. Overall, molecular cytogenetics is far from being outdated and actively involved in up-to-date diagnostics and research.

Parental Origin of the RB1 Gene Mutations in Families with Low Penetrance Hereditary Retinoblastoma

Our aim was to identify RB1 alterations causing hereditary low penetrance retinoblastoma and to evaluate how the parental origin of an RB1 mutation affects its phenotypic expression. By NGS and MLPA, RB1 mutations were found in 191 from 332 unrelated retinoblastoma patients. Among patients with identified RB1 mutations but without clinical family history of retinoblastoma, 7% (12/175) were found to have hereditary disease with one of the parents being an asymptomatic carrier of an RB1 mutation. Additionally, in two families with retinoblastoma history, mutations were inherited by probands from unaffected parents. Overall, nine probands inherited RB1 mutations from clinically unaffected fathers and five, from mothers. Yet, we gained explanations of maternal “unaffectedness” in most cases, either as somatic mosaicism or as clinical presentation of retinomas in involution, rendering the proportion of paternal to maternal truly asymptomatic mutation carriers as 9:1 (p = 0.005). This observation supports an assumption that parental origin of an RB1 mutation influences the likelihood of developing retinoblastoma. Additionally, our study revealed a relatively high frequency of asymptomatic carriage of the RB1 mutations among the parents of retinoblastoma patients, highlighting the utmost necessity of molecular analysis among the probands’ relatives irrespective of their clinical status and family history of retinoblastoma.

The genetic variation and relationship among the natural hybrids of Mangifera casturi Kosterm

Mangifera casturi Kosterm., a mango plant from Kalimantan Selatan, Indonesia, has limited genetic information, severely limiting the research on its genetic variation and phylogeny. We collected M. casturi’s genomic information using next-generation sequencing, developed microsatellite markers and performed Sanger sequencing for DNA barcoding analysis. These markers were used to confirm parental origin and genetic diversity of M. casturi hybrids. The clean reads of the Kasturi accession were assembled de novo, producing 259 872 scaffolds (N50 = 1 445 bp). Fourteen polymorphic microsatellite markers were developed from 11 040 microsatellite motif-containing sequences. In total, 58 alleles were produced with a mean of 4.14 alleles per locus. Microsatellite marker analysis revealed broad genetic variation in M. casturi. Phylogenetic analysis was performed using internal transcribed spacers (ITS), matK, rbcL, and trnH-psbA. The phylogenetic tree of chloroplast markers placed Kasturi, Cuban, Pelipisan, Pinari, and Hambawang in one group, with M. indica as the female ancestor. Meanwhile, the phylogenetic tree of ITS markers indicated several Mangifera species as ancestors of M. casturi. Thus, M. casturi very likely originated from the cross-hybridization of multiple ancestors. Furthermore, crossing the F1 hybrids of M. indica and M. quadrifida with other Mangifera spp. may have generated much genetic variation. The genetic information for M. casturi will be a resource for breeding improvement, and conservation studies.

The Contribution of QF-PCR and Pathology Studies in the Diagnosis of Diandric Triploidy/Partial Mole

Objective: the aim of our study was to assess the contribution of quantitative fluorescent polymerase chain reaction (QF-PCR) and pathology studies in the diagnosis of diandric triploidies/partial hydatidiform moles. Methods: this study included all fet al triploidies diagnosed by QF-PCR in chorionic villi or amniotic fluid in the 2 centers of BCNatal in which a maternal saliva sample was used to establish its parental origin. Pathology studies were performed in products of conception and concordance between a partial hydatidiform mole diagnosis and the finding of a diandric triploidy was assessed. Results: among 46 fetal triploidies, found in 13 ongoing pregnancies and in 33 miscarriages, there were 26 (56%) diandric triploidies. Concordant molecular (diandric triploidy) and pathology results (partial mole) were achieved in 14 cases (54%), while in 6 cases (23%) pathology studies were normal, and in the remaining 6 cases (23%) pathology studies could not be performed because miscarriage was managed medically. Conclusions: diandric triploidy is associated with partial hydatidiform mole and its diagnosis is crucial to prevent the development of persistent trophoblastic disease. QF-PCR analysis in chorionic villi or amniotic fluid provides a more accurate diagnosis of the parental origin of triploidy than the classical pathology studies.

Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression

ABSTRACTAllele-specific expression (ASE) is a phenomenon where one allele is preferentially expressed over the other. Genetic and epigenetic factors cause ASE by altering the final allelic composition of a gene’s product, leading to expression imbalances that can have functional consequences on phenotypes. Environmental signals also impact allele-specific gene regulation, but how they contribute to this crosstalk remains understudied. Here, we explored how allelic genotype, parent-of-origin, tissue type, sex, and dietary fat simultaneously influence ASE biases in a F1 reciprocal cross mouse model. Male and female mice from a F1 reciprocal cross of the LG/J and SM/J strains were fed a high-fat or low-fat diet. We harnessed strain-specific variants to distinguish between two classes of ASE: parent-of-origin dependent (unequal expression based on an allele’s parental origin) and sequence dependent (unequal expression based on an allele’s nucleotide identity). We present a comprehensive genome-wide map of ASE patterns across three metabolically-relevant tissues and nine environmental contexts. We find that both ASE classes are highly dependent on tissue type and environmental context. They vary across metabolic tissues, between males and females, and in response to dietary fat levels. Surprisingly, we also find several genes with inconsistent ASE biases that switched direction across tissues and/or contexts (e.g. SM/J biased in one cohort, LG/J biased in another). Together, our results provide novel insights into how genetic, epigenetic, and environmental mechanisms govern allele-specific gene regulation, which is an essential step towards deciphering the genotype to phenotype map.

Plasticity of Porites astreoides Early Life History Stages Suggests Mesophotic Coral Ecosystems Act as Refugia in Bermuda

As the devastating impacts of global climate change and local anthropogenic stressors on shallow-water coral reefs are expected to rise, mesophotic coral ecosystems have increasingly been regarded as potential lifeboats for coral survival, providing a source of propagules to replenish shallower reefs. Yet, there is still limited knowledge of the capacity for coral larvae to adjust to light intensities that change with depth. This study elucidates the mechanisms underlying plasticity during early life stages of the coral Porites astreoides that enable survival across broad depth gradients. We examined physiological and morphological variations in larvae from shallow (8–10 m) and mesophotic (45 m) reefs in Bermuda, and evaluated differences in survival, settlement patterns and size among recruits depending on light conditions using a reciprocal ex situ transplantation experiment. Larvae released from mesophotic adults were found to have significantly lower respiration rates and were significantly larger than those derived from shallow adults, indicating higher content of energetic resources and suggesting a greater dispersal potential for mesophotic larvae compared to their shallow counterparts. Additionally, larvae released from mesophotic adults experienced higher settlement success and larger initial spat size compared to larvae from shallow adults, demonstrating a potential connection between parental origin, offspring quality, and recruitment success. Although both shallow and mesophotic larvae exhibited the capacity to survive and settle under reciprocal light conditions, all larvae had higher survival under mesophotic light conditions regardless of parental origin, suggesting that conditions experienced under low light may enable longer larval life, further extending the dispersal period. These results indicate that larvae from mesophotic Porites astreoides colonies are likely capable of reseeding shallow reefs in Bermuda, thereby supporting the Deep Reef Refugia Hypothesis.