A Consensus Genetic Map and Linkage Panel for Fresh-market Tomato

The first consensus genetic map in fresh-market tomato (Solanum lycopersicum) was constructed, combining genetic recombination data from two biparental F2 segregating populations derived from four different fresh-market tomatoes. Each F2 population was nominated by different academic tomato breeding programs located in major fresh-market tomato-producing areas of the United States, and chromosome-wide variation in recombination rates was observed between tomato populations based on the origin of their breeding programs. A consensus map constructed using 335 common single nucleotide polymorphism (SNP) sites found in both populations spanned 737.3 cM across 12 tomato chromosomes, with chromosome 2 containing more than 40% of the total SNPs and chromosomes 4, 5, 7, and 10 together representing less than 10% of the SNPs. There was a high degree of collinearity between the genetic and physical positions of those 335 SNP markers. The integration of 6553 SNP sites that were detected in either of the two populations with 335 common sites resulted in an extended consensus genetic map. The total length of the extended map was estimated to be 1997.9 cM, which was compatible with a previous estimate for large-fruited fresh-market tomato. A linkage panel for fresh-market tomato was also established using the combined dataset of the consensus map of 335 SNP loci and 73 SNP-genotyped core fresh-market tomatoes. An empirical genetic mapping study of the tomato brachytic trait using the linkage panel demonstrated the value of the consensus map and linkage panel for tomato research. The allelic information in the linkage panel will serve as a basis for SNP marker implementation, such as genotyping platforms and genomic association map, in tomato.

Sex differences in white adipose tissue expansion: emerging molecular mechanisms

The escalating prevalence of individuals becoming overweight and obese is a rapidly rising global health problem, placing an enormous burden on health and economic systems worldwide. Whilst obesity has well described lifestyle drivers, there is also a significant and poorly understood component that is regulated by genetics. Furthermore, there is clear evidence for sexual dimorphism in obesity, where overall risk, degree, subtype and potential complications arising from obesity all differ between males and females. The molecular mechanisms that dictate these sex differences remain mostly uncharacterised. Many studies have demonstrated that this dimorphism is unable to be solely explained by changes in hormones and their nuclear receptors alone, and instead manifests from coordinated and highly regulated gene networks, both during development and throughout life. As we acquire more knowledge in this area from approaches such as large-scale genomic association studies, the more we appreciate the true complexity and heterogeneity of obesity. Nevertheless, over the past two decades, researchers have made enormous progress in this field, and some consistent and robust mechanisms continue to be established. In this review, we will discuss some of the proposed mechanisms underlying sexual dimorphism in obesity, and discuss some of the key regulators that influence this phenomenon.

Effects of Maternal Nutrition on Female Offspring Weight Gain and Sexual Development

Maternal nutrition during pregnancy influences postnatal life of animals; nevertheless, few studies have investigated its effects on the productive performance and reproductive development of heifers. This study evaluated the performance, reproductive development, and correlation between reproduction × fat thickness and performance × ribeye area (REA) traits of heifers. We also performed an exploratory genomic association during the rearing period in heifers submitted to fetal programming. The study comprised 55 Nellore heifers born to dams exposed to one of the following nutritional planes: control, without protein-energy supplementation; PELT, protein-energy last trimester, protein-energy supplementation offered in the final third of pregnancy; and PEWG, protein-energy whole gestation, protein-energy supplementation upon pregnancy confirmation. Protein-energy supplementation occurred at the level of 0.3% live weight. After weaning, heifers were submitted to periodic evaluations of weight and body composition by ultrasonography. From 12 to 18 months, we evaluated the reproductive tract of heifers to monitor its development for sexual precocity and ovarian follicle population. The treatments had no effect (p > 0.05) on average daily gain; however, the weight of the animals showed a significant difference over time (p = 0.017). No differences were found between treatments for REA, backfat, and rump fat thickness, nor for puberty age, antral follicular count, and other traits related to reproductive tract development (p > 0.05). The correlation analysis between performance traits and REA showed high correlations (r > 0.37) between REA at weaning and year versus weight from weaning until yearling; however, no correlation was found for reproductive development traits versus fat thickness (p > 0.05). The exploratory genomic association study showed one single-nucleotide polymorphism (SNP) for each treatment on an intergenic region for control and PEWG, and the one for PELT on an intronic region of RAPGEF1 gene. Maternal nutrition affected only the weight of the animals throughout the rearing period.

A Genome-First Approach to Rare Variants in Dominant Postlingual Hearing Loss Genes in a Large Adult Population

Objective To investigate the importance of rare variants in adult-onset hearing loss. Study Design Genomic association study. Setting Large biobank from tertiary care center. Methods We investigated rare variants (minor allele frequency <5%) in 42 autosomal dominant (DFNA) postlingual hearing loss (HL) genes in 16,657 unselected individuals in the Penn Medicine Biobank. We determined the prevalence of known pathogenic and predicted deleterious variants in subjects with audiometric-proven sensorineural hearing loss. We scanned across known postlingual DFNA HL genes to determine those most significantly contributing to the phenotype. We replicated findings in an independent cohort (UK Biobank). Results While rare individually, when considering the accumulation of variants in all postlingual DFNA genes, more than 90% of participants carried at least 1 rare variant. Rare variants predicted to be deleterious were enriched in adults with audiometric-proven hearing loss (pure-tone average >25 dB; P = .015). Patients with a rare predicted deleterious variant had an odds ratio of 1.27 for HL compared with genotypic controls ( P = .029). Gene burden in DIABLO, PTPRQ, TJP2, and POU4F3 were independently associated with sensorineural hearing loss. Conclusion Although prior reports have focused on common variants, we find that rare predicted deleterious variants in DFNA postlingual HL genes are enriched in patients with adult-onset HL in a large health care system population. We show the value of investigating rare variants to uncover hearing loss phenotypes related to implicated genes.

Genomic Association vs. Serological Determination of ABO Blood Types in a Chinese Cohort, with Application in Mendelian Randomization

ABO blood system is an inborn trait determined by the ABO gene. The genetic-phenotypic mechanism underneath the four mutually exclusive and collectively exhaustive types of O, A, B and AB could theoretically be elucidated. However, genetic polymorphisms in the human populations render the link elusive, and importantly, past studies using genetically determined rather than biochemically determined ABO types were not and could not be evaluated for the inference errors. Upon both blood-typing and genotyping a cohort of 1008 people of the Han Chinese population, we conducted a genome-wide association study in parallel with both binomial and multinomial log-linear models. Significant genetic variants are all mapped to the ABO gene, and are quantitatively evaluated for binary and multi-class classification performances. Three single nucleotide polymorphisms of rs8176719, rs635634 and rs7030248 would together be sufficient to establish a multinomial predictive model that achieves high accuracy (0.98) and F1 scores (micro 0.99 and macro 0.97). Using the set of identified ABO-associated genetic variants as instrumental variables, we demonstrate the application in causal analysis by Mendelian randomization (MR) studies on blood pressures (one-sample MR) and severe COVID-19 with respiratory failure (two-sample MR).