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Hierarchical properties characterize elephant fission -fusion social organization whereby stable groups of individuals coalesce into higher order groups or split in a predictable manner. This hierarchical complexity is rare among animals and, as such, an examination of the factors driving its emergence offers unique insight into the evolution of social behaviour. Investigation of the genetic basis for such social affiliation demonstrates that while the majority of core social groups (second-tier affiliates) are significantly related, this is not exclusively the case. As such, direct benefits received through membership of these groups appear to be salient to their formation and maintenance. Further analysis revealed that the majority of groups in the two higher social echelons (third and fourth tiers) are typically not significantly related. The majority of third-tier members are matrilocal, carrying the same mtDNA control region haplotype, while matrilocality among fourth-tier groups was slightly less than expected at random. Comparison of results to those from a less disturbed population suggests that human depredation, leading to social disruption, altered the genetic underpinning of social relations in the study population. These results suggest that inclusive fitness benefits may crystallize elephant hierarchical social structuring along genetic lines when populations are undisturbed. However, indirect benefits are not critical to the formation and maintenance of second-, third-or fourth-tier level bonds, indicating the importance of direct benefits in the emergence of complex, hierarchical social relations among elephants. Future directions and conservation implications are discussed.

Genetic studies concerned with the demographic history of wildlife species can help elucidate the role of climate change and other forces such as human activity in shaping patterns of divergence and distribution. The African buffalo (Syncerus caffer) declined dramatically during the rinderpest pandemic in the late 1800s, but little is known about the earlier demographic history of the species. We analysed genetic variation at 17 microsatellite loci and a 302-bp fragment of the mitochondrial DNA control region to infer past demographic changes in buffalo populations from East Africa. Two Bayesian coalescent-based methods as well as traditional bottleneck tests were applied to infer detailed dynamics in buffalo demographic history. No clear genetic signature of population declines related to the rinderpest pandemic could be detected. However, Bayesian coalescent modelling detected a strong signal of African buffalo population declines in the order of 75-98%, starting in the mid-Holocene (approximately 3-7000 years ago). The signature of decline was remarkably consistent using two different coalescent-based methods and two types of molecular markers. Exploratory analyses involving various prior assumptions did not seriously affect the magnitude or timing of the inferred population decline. Climate data show that tropical Africa experienced a pronounced transition to a drier climate approximately 4500 years ago, concurrent with the buffalo decline. We therefore propose that the mid-Holocene aridification of East Africa caused a major decline in the effective population size of the buffalo, a species reliant on moist savannah habitat for its existence.

Two hundred years of elephant hunting for ivory, peaking in 1970-1980s, caused local extirpations and massive population declines across Africa. The resulting genetic impacts on surviving populations have not been studied, despite the importance of understanding the evolutionary repercussions of such human-mediated events on this keystone species. Using Bayesian coalescent-based genetic methods to evaluate time-specific changes in effective population size, we analysed genetic variation in 20 highly polymorphic microsatellite loci from 400 elephants inhabiting the greater Samburu-Laikipia region of northern Kenya. This area experienced a decline of between 80% and 90% in the last few decades when ivory harvesting was rampant. The most significant change in effective population size, however, occurred approximately 2500 years ago during a mid-Holocene period of climatic drying in tropical Africa. Contrary to expectations, detailed analyses of four contemporary age-based cohorts showed that the peak poaching epidemic in the 1970s caused detectable temporary genetic impacts, with genetic diversity rebounding as juveniles surviving the poaching era became reproductively mature. This study demonstrates the importance of climatic history in shaping the distribution and genetic history of a keystone species and highlights the utility of coalescent-based demographic approaches in unravelling ancestral demographic events despite a lack of ancient samples. Unique insights into the genetic signature of mid-Holocene climatic change in Africa and effects of recent poaching pressure on elephants are discussed.

Purpose This study investigated the diagnostic utility of nontargeted genomic testing in patients with pediatric heart disease. Methods We analyzed genome sequencing data of 111 families with cardiac lesions for rare, disease-associated variation. Results In 14 families (12.6%), we identified causative variants: seven were de novo (ANKRD11, KMT2D, NR2F2, POGZ, PTPN11, PURA, SALL1) and six were inherited from parents with no or subclinical heart phenotypes (FLT4, DNAH9, MYH11, NEXMIF, NIPBL, PTPN11). Outcome of the testing was associated with the presence of extracardiac features (p = 0.02), but not a positive family history for cardiac lesions (p = 0.67). We also report novel plausible gene–disease associations for tetralogy of Fallot/pulmonary stenosis (CDC42BPA, FGD5), hypoplastic left or right heart (SMARCC1, TLN2, TRPM4, VASP), congenitally corrected transposition of the great arteries (UBXN10), and early-onset cardiomyopathy (TPCN1). The identified candidate genes have critical functions in heart development, such as angiogenesis, mechanotransduction, regulation of heart size, chromatin remodeling, or ciliogenesis. Conclusion This data set demonstrates the diagnostic and scientific value of genome sequencing in pediatric heart disease, anticipating its role as a first-tier diagnostic test. The genetic heterogeneity will necessitate large-scale genomic initiatives for delineating novel gene–disease associations.

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Cancer biomarker studies often require nucleic acid extraction from limited amounts of formalin-fixed, paraffin-embedded (FFPE) tissues, such as histologic sections or needle cores. A major challenge is low quantity and quality of extracted nucleic acids, which can limit our ability to perform genetic analyses, and have a significant influence on overall study design. This study was aimed at identifying the most reliable and reproducible method of obtaining sufficient high-quality nucleic acids from FFPE tissues. We compared the yield and quality of nucleic acids from 0.6-mm FFPE prostate tissue cores across 16 DNA and RNA extraction protocols, using 14 commercially available kits. Nucleic acid yield was determined by fluorometry, and quality was determined by spectrophotometry. All protocols yielded nucleic acids in quantities that are compatible with downstream molecular applications. However, the protocols varied widely in the quality of the extracted RNA and DNA. Four RNA and five DNA extraction protocols, including protocols from two kits for dual-extraction of RNA and DNA from the same tissue source, were prioritized for further quality assessment based on the yield and purity of their products. Specifically, their compatibility with downstream reactions was assessed using both NanoString nCounter gene expression assays and reverse-transcriptase real-time PCR for RNA, and methylation-specific PCR assays for DNA. The kit deemed most suitable for FFPE tissue was the AllPrep kit by Qiagen because of its yield, quality, and ability to purify both RNA and DNA from the same sample, which would be advantageous in biomarker studies.

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