Kin-Aggregations Explain Chaotic Genetic Patchiness, a Commonly Observed Genetic Pattern, in a Marine Fish

The phenomenon of chaotic genetic patchiness is a pattern commonly seen in marine organisms, particularly those with demersal adults and pelagic larvae. This pattern is usually associated with sweepstakes recruitment and variable reproductive success. Here we investigate the biological underpinnings of this pattern in a species of marine goby Coryphopterus personatus. We find that populations of this species show tell-tale signs of chaotic genetic patchiness including: small, but significant, differences in genetic structure over short distances; a non-equilibrium or “chaotic” pattern of differentiation among locations in space; and within locus, within population deviations from the expectations of Hardy-Weinberg equilibrium (HWE). We show that despite having a pelagic larval stage, and a wide distribution across Caribbean coral reefs, this species forms groups of highly related individuals at small spatial scales (metres). These spatially clustered family groups cause the observed deviations from HWE and local population differentiation, a finding that is rarely demonstrated, but could be more common than previously thought

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Kin-Aggregations Explain Chaotic Genetic Patchiness, a Commonly Observed Genetic Pattern, in a Marine Fish - Fig 3

<p>Mean pairwise relatedness () values by geographic sample (A) and cluster (B) with standard errors. The shaded region indicates the area within the 95% confidence intervals calculated using a permutation test with 1,000 iterations. Triangles in 3B indicate proportion of full and half-sibs within the cluster with shaded symbols indicating significantly elevated transitivity when compared to randomly generated networks equivalent to those observed in the clusters.</p

Relatedness and sibship summary of genetic clusters within sample sites.

<p>Relatedness and sibship summary of genetic clusters within sample sites.</p

PCR Conditions and locus summary statistics.

<p>PCR Conditions and locus summary statistics.</p

Regression plot showing locus specific sample proportion of individuals which failed to amplify plotted against the absolute value of the difference between expected and observed heterozygosity.

<p>The plotted line is the result of a linear regression (F_(1,88) = 0.0018, p = 0.97) with the shaded area indicating the 95% confidence intervals. Blue points are locus by sample combinations which were not significantly different from the expectations of HWE based on exact tests. Red points are locus by sample combinations which are significantly deviated from the expectations of HWE based on exact tests.</p

The Mesoamerican Barrier Reef study sites: BC–Banco Chinchorro, Mexico; BBR–Belizean barrier reef, Belize; TA–Turneffe Atoll, Belize; RO–Roatán, Honduras.

<p>Insets show scatter plots (and density plots in the case of two clusters) of clusters from DAPC analysis within sampling locations. The axes of the plots are the first two discriminant functions used to delineate clusters with inertia ellipses representing 67% of the variance. The end of the lines connected to the centre of each inertia ellipse represent individuals plotted on each discriminant function and denotes cluster membership. In locations with only two clusters present there is only one discriminant function, as such density plots of proportion of individuals present at each value of the discriminant function were included to show cluster separation. Numbers in parentheses indicate how many individuals were collected from each location.</p

Genetic diversity across the mitochondrial genome of eastern oysters (Crassostrea virginica) in the northern Gulf of Mexico

The eastern oyster, Crassostrea virginica, is divided into four populations along the western North Atlantic, however, the only published mitochondrial genome sequence was assembled using one individual in Delaware. This study aimed to 1) assemble C. virginica mitochondrial genomes from Texas with pooled restriction-site-associated DNA sequence (ezRAD), 2) evaluate the validity of the mitochondrial genome assemblies including comparison with Sanger sequencing data, and 3) evaluate genetic differentiation both between the Delaware and Texas genomes, as well as among three bays in Texas. The pooled-genome-assembled-genomes (PAGs) from Texas exhibited several characteristics indicating that they were valid, including elevated nucleotide diversity in non-coding and the third position of codons, placement as the sister haplotype of the genome from Delaware in a phylogenetic reconstruction of Crassostrea mitochondrial genomes, and a lack of genetic structure in the ND4 gene among the three Texas bays as was found with Sanger amplicons in samples from the same bays several years prior. In the comparison between the Delaware and Texas genome, 27 of 38 coding regions exhibited variability between the two populations, which were differentiated by 273 mutations, versus 1-13 mutations among the Texas samples. Using the full PAGs, there was no additional evidence for population structure among the three Texas bays. While population genetics is rapidly moving towards larger high-density datasets, studies of mitochondrial DNA (and genomes) can be particularly useful for comparing historic data prior to the modern era of genomics. As such, being able to reliably compile mitochondrial genomes from genomic data can improve the ability to compare results across studies