Molecular and Historical Aspects of Corn Belt Dent Diversity

Tens-of-thousands of open-pollinated cultivars of corn (Zea mays L.) are being maintained in germplasm banks. Knowledge of the amount and distribution of genetic variation within and among accessions can aid end users in choosing among them. We estimated molecular genetic variation and looked for influences of pedigree, adaptation, and migration in the genetic makeup of conserved Corn-Belt Dent-related germplasm. Plants sampled from 57 accessions representing Corn-Belt Dents, Northern Flints, Southern Dents, plus 12 public inbreds, were genotyped at 20 simple sequence repeat (SSR) loci. For 47 of the accessions, between 5 and 23 plants per accession were genotyped (mean = 9.3). Mean number of alleles per locus was 6.5 overall, 3.17 within accessions, and 3.20 within pooled inbreds. Mean gene diversity was 0.53 within accessions and 0.61 within pooled inbreds. Open-pollinated accessions showed a tendency toward inbreeding (FIS = 0.09), and 85% of genetic variation was shared among them. A Fitch-Margoliash tree strongly supported the distinctiveness of flint from dent germplasm but did not otherwise reveal evidence of genetic structure. Mantel tests revealed significant correlations between genetic distance and geographical (r = 0.54, P= 0.04) or maturity zone (r = 0.33, P = 0.03) distance only if flint germplasm was included in the analyses. A significant correlation (r = 0.76, P \u3c 0.01) was found between days to pollen shed and maturity zone of accession origin. Pedigree, rather than migration or selection, has most influenced the genetic structure of the extant representatives of the open-pollinated cultivars at these SSR loci

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Genetic insights into resting heart rate and its role in cardiovascular disease.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development