On the survival of a gene represented in a founder population

Gene survival in a population which increases without density dependence is considered using a generalization of the Moran model for haploid individuals. It is shown that situations where ultimate homozygosity is certain and where there is a non-zero probability of balanced polymorphism are both possible. Necessary and sufficient conditions in terms of the mean of the population growth distribution are given which determine which of these situations holds.     

Respiratory cytochrome c oxidase can be efficiently reduced by the photosynthetic redox proteins cytochrome c6 and plastocyanin in cyanobacteria

Plastocyanin and cytochrome c6 are two small soluble electron carriers located in the intrathylacoidal space of cyanobacteria. Although their role as electron shuttle between the cytochrome b6f and photosystem I complexes in the photosynthetic pathway is well established, their participation in the respiratory electron transport chain as donors to the terminal oxidase is still under debate. Here, we present the first time-resolved analysis showing that both cytochrome c6 and plastocyanin can be efficiently oxidized by the aa3 type cytochrome c oxidase in Nostoc sp. PCC 7119. The apparent electron transfer rate constants are ca. 250 and 300 s(-1) for cytochrome c6 and plastocyanin, respectively. These constants are 10 times higher than those obtained for the oxidation of horse cytochrome c by the oxidase, in spite of being a reaction thermodynamically more favourable.     

Characterizing homozygosity across United States,New Zealand and Australian Jersey cow and bull populations

Background

Dairy cattle breeding objectives are in general similar across countries, but environment and management conditions may vary, giving rise to slightly different selection pressures applied to a given trait. This potentially leads to different selection pressures to loci across the genome that, if large enough, may give rise to differential regions with high levels of homozygosity. The objective of this study was to characterize differences and similarities in the location and frequency of homozygosity related measures of Jersey dairy cows and bulls from the United States (US), Australia (AU) and New Zealand (NZ).

Results

The populations consisted of a subset of genotyped Jersey cows born in US (n = 1047) and AU (n = 886) and Jersey bulls progeny tested from the US (n = 736), AU (n = 306) and NZ (n = 768). Differences and similarities across populations were characterized using a principal component analysis (PCA) and a run of homozygosity (ROH) statistic (ROH45), which counts the frequency of a single nucleotide polymorphism (SNP) being in a ROH of at least 45 SNP. Regions that exhibited high frequencies of ROH45 and those that had significantly different ROH45 frequencies between populations were investigated for their association with milk yield traits. Within sex, the PCA revealed slight differentiation between the populations, with the greatest occurring between the US and NZ bulls. Regions with high levels of ROH45 for all populations were detected on BTA3 and BTA7 while several other regions differed in ROH45 frequency across populations, the largest number occurring for the US and NZ bull contrast. In addition, multiple regions with different ROH45 frequencies across populations were found to be associated with milk yield traits.

Conclusion

Multiple regions exhibited differential ROH45 across AU, NZ and US cow and bull populations, an interpretation is that locations of the genome are undergoing differential directional selection. Two regions on BTA3 and BTA7 had high ROH45 frequencies across all populations and will be investigated further to determine the gene(s) undergoing directional selection.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1352-4) contains supplementary material, which is available to authorized users.     

Uniparental disomy analysis in trios using genome-wide SNP array and whole-genome sequencing data imply segmental uniparental isodisomy in general populations

Whole chromosomal and segmental uniparental disomy (UPD) is one of the causes of imprinting disorder and other recessive disorders. Most investigations of UPD were performed only using cases with relevant phenotypic features and included few markers. However, the diagnosis of cases with segmental UPD requires a large number of molecular investigations. Currently, the accurate frequency of whole chromosomal and segmental UPD in a normal developing embryo is not well understood. Here, we present whole chromosome and segmental UPD analysis using single nucleotide polymorphism (SNP) microarray data of 173 mother-father-child trios (519 individuals) from six populations (including 170 HapMap trios). For two of these trios, we also investigated the possibility of shorter segmental UPD as a consequence of homologous recombination repair (HR) for DNA double strand breaks (DSBs) during the early developing stage using high-coverage whole-genome sequencing (WGS) data from 1000 Genomes Project. This could be overlooked by SNP microarray. We identified one obvious segmental paternal uniparental isodisomy (iUPD) (8.2 mega bases) in one HapMap sample from 173 trios using Genome-Wide Human SNP Array 6.0 (SNP6.0 array) data. However, we could not identify shorter segmental iUPD in two trios using WGS data. Finally, we estimated the rate of segmental UPD to be one per 173 births (0.578%) based on the UPD screening for 173 trios in general populations. Based on the autosomal chromosome pairs investigated, we estimate the rate of segmental UPD to be one per 3806 chromosome pairs (0.026%). These data imply the possibility of hidden segmental UPD in normal individuals.     

Genetic variants in BMP8B gene are associated with growth traits in Chinese native cattle

As a signaling molecule, bone morphogenetic protein 8B (BMP8B) plays an essential role in bone metabolism and is able to regulate thermogenesis and energy balance, which suggests that BMP8B gene may be a new candidate for growth traits. Here, to characterize the effects of BMP8B gene on growth traits, we first used three Chinese indigenous cattle breeds (n = 845) to detect single nucleotide polymorphisms (SNPs). Five novel SNPs of BMP8B gene (g.− 242C>T, g.2164C>T, g.2639T>C, g.2900C>G and g.10817C>T) were identified by DNA pool sequencing and forced PCR–RFLP. And then we associated the five SNPs with four growth traits (body weight, body length, heart girth, and hucklebone width). Results from association analysis showed that the SNPs 1, 2, and 3 affected growth trait(s) markedly (P < 0.05). Further, 6 combined haplotypes were constructed to guarantee the reliability of analysis results. There were also significant differences in body length, heart girth and body weight between the 6 combined haplotypes (P < 0.05), but not in hucklebone width (P > 0.05). Collectively, our results suggest a modulatory role of BMP8B gene in cattle growth and development, and 3 SNPs could be used as molecular markers in early marker assisted selection (MAS) in beef cattle breeding program.     

Haplotype structure,adaptive history and associations with exploratory behaviour of the DRD4 gene region in four great tit (Parus major) populations

The assessment of genetic architecture and selection history in genes for behavioural traits is fundamental to our understanding of how these traits evolve. The dopamine receptor D4 (DRD4) gene is a prime candidate for explaining genetic variation in novelty seeking behaviour, a commonly assayed personality trait in animals. Previously, we showed that a single nucleotide polymorphism in exon 3 of this gene is associated with exploratory behaviour in at least one of four Western European great tit (Parus major) populations. These heterogeneous association results were explained by potential variable linkage disequilibrium (LD) patterns between this marker and the causal variant or by other genetic or environmental differences among the populations. Different adaptive histories are further hypothesized to have contributed to these population differences. Here, we genotyped 98 polymorphisms of the complete DRD4 gene including the flanking regions for 595 individuals of the four populations. We show that the LD structure, specifically around the original exon 3 SNP is conserved across the four populations and does not explain the heterogeneous association results. Study‐wide significant associations with exploratory behaviour were detected in more than one haplotype block around exon 2, 3 and 4 in two of the four tested populations with different allele effect models. This indicates genetic heterogeneity in the association between multiple DRD4 polymorphisms and exploratory behaviour across populations. The association signals were in or close to regions with signatures of positive selection. We therefore hypothesize that variation in exploratory and other dopamine‐related behaviour evolves locally by occasional adaptive shifts in the frequency of underlying genetic variants.     

A new likelihood estimator and its comparison with moment estimators of individual genome-wide diversity

The inbreeding coefficient of an individual, F, is one of the central parameters in population genetics theory. It has found important applications in evolutionary biology, conservation and ecology, such as the study of inbreeding depression. In the absence of detailed and reliable pedigree records, researchers have developed quite a few estimators to estimate F or the genome-wide homozygosity from genetic marker data. The statistical properties and comparative performances of these metrics are rarely known, however, which impedes an informed choice of the most appropriate one in practical applications. In this investigation, I propose a new likelihood F estimator that makes efficient use of marker information and takes into account of allelic dropouts, null alleles and prior knowledge of inbreeding. I compare the likelihood estimator with three moment estimators of F and three metrics of genomic homozygosity (or heterozygosity) by analysing both simulated and empirical datasets. It is shown that the likelihood estimator invariably outperforms the other estimators and metrics across all datasets analysed. For a typical dataset in heterozygosity-fitness correlation studies involving 10-20 microsatellites and 50 individuals, the correlation between the likelihood estimator and F (the simulated true inbreeding coefficient) is about 8 ～ 35% higher than that between the moment estimators and F. A frequently applied metric, multilocus heterozygosity (MLH), and an F estimator based on the consideration of the proportion of alleles in homozygous conditions, [F R'), are shown to have particularly poor performances. The low correlation between MLH and fitness traits, which is widely observed in numerous empirical studies, might be partially caused by the adoption of this inefficient estimator of genomic inbreeding.     

The cold denatured state is compact but expands at low temperatures: hydrodynamic properties of the cold denatured state of the C-terminal domain of L9

A point mutation of a small globular protein, the C-terminal domain of L9 destabilizes the protein and leads to observable cold-denaturation at temperatures above zero. The cold denatured state is in slow exchange with the native state on the NMR time scale, and this allows the hydrodynamic properties of the cold unfolded state and the native state to be measured under identical conditions using pulsed-field gradient NMR diffusion measurements. This provides the first experimental measurement of the hydrodynamic properties of a cold unfolded protein and its folded form under identical conditions. Hydrodynamic radii of the cold-induced unfolded states were measured for a set of temperatures ranging from 2 °C to 25 °C at pD 6.6 in the absence of denaturant. The cold unfolded state is compact compared to the urea or acid unfolded state and a trend of increasing radii of hydration is observed as the temperature is lowered. These observations are confirmed by experiments on the same protein at pD 8.0, where it is more stable, in the presence of a modest concentration of urea. The expansion of the cold-denatured state at lower temperatures is consistent with the temperature dependence of hydrophobic interactions.     

Application of Short Tandem Repeat markers in diagnosis of chromosomal aneuploidies and forensic DNA investigation in Pakistan

Purpose

Short Tandem Repeat (STR) genetic markers hold great potential in forensic investigations, molecular diagnostics and molecular genetics research. AmpFlSTR® Identifiler™ PCR amplification kit is a multiplex system for co-amplification of 15 STR markers used worldwide in forensic investigations. This study attempts to assess forensic validity of these STRs in Pakistani population and to investigate its applicability in quick and simultaneous diagnosis and tracing parental source of common chromosomal aneuploidies.

Methodology

Samples from 554 healthy Pakistani individuals from 5 different ethnicities were analyzed for forensic parameters using Identifiler STRs and 74 patients' samples with different aneuploidies were evaluated for diagnostic strengths of these markers.

Results

All STRs hold sufficient forensic applicability in Pakistani population with paternity index between 1.5 and 3.5, polymorphic information content from 0.63 to 0.87 and discrimination power ≥ 0.9 (except TPOX locus). Variation from Hardy–Weinberg equilibrium was observed at some loci reflecting selective breeding and intermarriages trend in Pakistan. Among aneuploidic samples, all trisomies were precisely detectable while aneuploidies involving sex chromosomes or missing chromosomes were not clearly detectable using Identifiler STRs. Parental origin of aneuploidy was traceable in 92.54% patients.

Conclusion

The studied STR markers are valuable tools for forensic application in Pakistan and utilizable for quick and simultaneous identification of some common trisomic conditions. Adding more sex chromosome specific STR markers can immensely increase the diagnostic and forensic potential of this system.