Widespread genetic testing control inherited polycystic kidney disease in cats

Background/Objectives: Horseshoe kidney is a congenital anomaly characterized by the fusion of the kidneys at the lower pole. Polycystic kidney disease with horseshoe kidney is called polycystic horseshoe kidney. Genetic testing is essential for the diagnosis of polycystic horseshoe kidney disease because it can result from a number of genetic disorders. Fewer than 20 cases of polycystic horseshoe kidney have been reported to date. However, polycystic horseshoe kidney disease was mostly diagnosed via autopsy or radiologic imaging techniques including computed tomography, magnetic resonance imaging, and angiography. Because polycystic kidney disease has various causes, genetic testing is essential for the diagnosis of autosomal dominant polycystic kidney disease (ADPKD) in patients with polycystic horseshoe kidney disease. At present, the diagnosis of ADPKD is made using genetic approaches, including next-generation sequencing. We reported a potentially pathogenic polycystin 1 (PKD1) gene in a patient with ADPKD and horseshoe kidney. Methods: We performed the sequencing of the PKD1 gene and radiological examinations (computed abdominal tomography). Results: Computed abdominal tomography revealed enlarged kidneys with multiple cysts fused at the lower poles, indicating polycystic HSK. The sequencing of the PKD1 gene revealed a heterozygous pathogenic variant c.165_171del (p.Leu56ArgfsTer15), which genetically confirmed the diagnosis of ADPKD. The patient was treated with an angiotensin II receptor blocker. Conclusions: In this case report, we suggest that genetic testing becomes the key approach to the diagnosis of ADPKD with horseshoe kidney. Additionally, this approach offers the benefit of avoiding the possibility of the condition being mistakenly diagnosed or diagnosed late due to its uncommon occurrence and nonspecific symptoms.

Climate change is predicted to increase forest fires in boreal forests, which can threaten the sustainability of forest genetic resources. Wildfires can potentially impact genetic diversity and population structure in forest trees by creating population bottlenecks, and influencing demography, effective population size (Ne) and various evolutionary processes. We have investigated this critical issue in a widely-distributed, transcontinental, ecologically and economically important and fire-intolerant boreal conifer, white spruce (Picea glauca (Moench) Voss). We tested the hypothesis that in a predominantly outcrossing species with long distance gene flow, such as white spruce, located in primary undisturbed forests, normal forest fires do not adversely affect genetic diversity and population structure. We used 10 nuclear genic and genomic microsatellite loci to examine genetic diversity and population structure of post-fire pristine old-growth (PF-OG) and adjacent post-fire naturally regenerated young (PF-YR) stands. The genetic diversity, inbreeding and genetic differentiation levels, Bayesian population structure, Ne and latent genetic potential were statistically similar between the PF-OG and PF-YR populations. None of the microsatellites showed any signature of selection. Our study demonstrates that normal wild forest fires do not adversely affect genetic diversity, differentiation, and population genetic structure in white spruce. The results should have wide significance for sustainable forest management.

Association of mutation position in polycystic kidney disease 1 ( PKD1) gene and development of a vascular phenotype

Female greater horseshoe bats form maternity colonies each summer in order to give birth and raise young. During the mating period, females visit males occupying territorial sites, copulation takes place and sperm are stored until ovulation occurs, normally in April. Using microsatellite markers and a likelihood method of parentage analysis, we studied breeding behaviour and male reproductive success over a five-year period in a population of bats in south-west Britain. Paternity was assigned with 80% confidence to 44% of young born in five successive cohorts. While a small annual skew in male reproductive success was detected, the variance increased over five years due to the repeated success of a few individuals. Mating was polygynous, although some females gave birth to offspring sired by the same male in separate years. Such repeated partnerships probably result from fidelity for either mating sites or individuals or from sperm competition. Females mated with males born both within and outside their own natal colony; however, relatedness between parents was no less than the average recorded for male female pairs. Gene flow between colonies is likely to be primarily mediated by both female and male dispersal during the mating period rather than more permanent movements.

Advances in molecular techniques have enabled the study of genetic diversity and population structure in many different contexts. Studies that assess the genetic structure of cetacean populations often use biopsy samples from free-ranging individuals and tissue samples from stranded animals or individuals that became entangled in fishery or aquaculture equipment. This leads to the question of how representative the location of a stranded or entangled animal is with respect to its natural range, and whether similar results would be obtained when comparing carcass samples with samples from free-ranging individuals in studies of population structure. Here we use tissue samples from carcasses of dolphins that stranded or died as a result of bycatch in South Australia to investigate spatial population structure in two species: coastal bottlenose (Tursiops sp.) and short-beaked common dolphins (Delphinus delphis). We compare these results with those previously obtained from biopsy sampled free-ranging dolphins in the same area to test whether carcass samples yield similar patterns of genetic variability and population structure. Data from dolphin carcasses were gathered using seven microsatellite markers and a fragment of the mitochondrial DNA control region. Analyses based on carcass samples alone failed to detect genetic structure in Tursiops sp., a species previously shown to exhibit restricted dispersal and moderate genetic differentiation across a small spatial scale in this region. However, genetic structure was correctly inferred in D. delphis, a species previously shown to have reduced genetic structure over a similar geographic area. We propose that in the absence of corroborating data, and when population structure is assessed over relatively small spatial scales, the sole use of carcasses may lead to an underestimate of genetic differentiation. This can lead to a failure in identifying management units for conservation. Therefore, this risk should be carefully assessed when planning population genetic studies of cetaceans.

Introduction: Polycystic kidney disease (PKD) is a genetic disorder that leads to the development of renal cysts and progressive chronic kidney disease. The primary genetic variants leading to PKD are PKD1 and PKD2, which encode for the protein polycystin-1. This protein is a building block for the architecture and function of the renal tubule. Disruption in the code affects the integrity of the renal parenchyma, leading to cyst formation and a decline in renal function over time. Case Description: A 41-year-old female presented for elevated serum creatinine and a significant family history of PKD in her father and son. Her father underwent nephrectomy of his native polycystic kidneys, and her son was diagnosed with PKD after a workup of microscopic hematuria. During her workup, she underwent a renal ultrasound (Figures 1a and 1b), which revealed PKD Mayo Clinic classification 1b with additional hepatic cysts. Laboratory testing showed declining renal function with an estimated glomerular filtration rate of 48 mL/min/1.73 m2. Genetic testing was performed that was absent any known pathogenic mutation. However, a variant of unknown significance was detected with a single heterozygous non-truncating variant in PKD1 c.11214C>G (p.Asn3738Lys) predicted to result in a single amino acid substitution of Asn to Lys at codon 3738 in exon 39. 5. Discussion with genetic testing laboratory director found that it would still take time to reclassify this variant as more data becomes available with a recommendation the patient's father and/or son also undergo genetic testing to better understand the clinical significance of this variant. Discussion: PKD varies in disease severity and progression due to the complex relationship between genetic variability and epigenetic factors. With a size of over 4000 amino acids, it has been observed that small changes have profound effects on the polycystin-1 function. This case highlights the identification of novel genetic variants with potential pathological effects in PKD and the importance of enhancing our understanding of the disease at a molecular level. Further studies would be necessary to evaluate the significance of this variant to the phenotypic development of PKD.

Effects of fifty years of shelterwood harvesting on genetic diversity and population structure of Oriental beech (Fagus orientalis L.) in the relict Hyrcanian forest

To determine the prevalence of feline polycstic kidney disease in Persian cats presented to the University of Melbourne Veterinary Clinic and Hospital between February and August 1999. A prospective clinical study using client owned animals was performed. Two hundred and fifty Persian cats, ranging in age from 13 weeks to 10 years, were presented to the University of Melbourne Veterinary Clinic and Hospital for ultrasound examination of both kidneys. The cats were placed in dorsal and lateral recumbency and alcohol and ultrasonic coupling gel were applied to the skin. The kidneys were examined ultrasonographically in longitudinal, sagittal and transverse planes. Results were recorded for each cat at the time of examination as either negative or positive for PKD. In addition 14 Exotics (short-haired Persians), 4 Ragdolls and 3 British Short-Hair cats were examined. Forty five percent of Persian cats examined were found to be positive for feline polycystic kidney disease on the basis of presence of anechoic cysts within the renal parenchyma. These cats ranged in age from 13 weeks to 10 years. Fifty per cent of the Exotic cats were positive for polycystic kidney disease whereas all Ragdolls and British Short Hairs were negative for the disease. Only one positive cat was reported to be showing clinical signs of renal disease. The prevalence of feline polycstic disease in Persian cats presented to the University of Melbourne between February and August 1999 was 45%. Exotic cats were found to have the slightly higher incidence of 50%.

Previous genetic studies of eastern coyotes ( Canis latrans ) are based on one of two strategies: sampling many individuals using one or very few molecular markers, or sampling very few individuals using many genomic markers. Thus, a regional analysis of genetic diversity and population structure in eastern coyotes using many samples and several molecular markers is lacking. I evaluated genetic diversity and population structure in 385 northeastern coyotes using 16 common single nucleotide polymorphisms (SNPs). A region-wide analysis of population structure revealed three primary genetic populations, but these do not correspond to the same three subdivisions inferred in a previous analysis of mitochondrial DNA sequences. More focused geographic analyses of population structure indicated that ample genetic structure occurs in coyotes from an intermediate contact zone where two range expansion fronts meet. These results demonstrate that genotyping several highly heterozygous SNPs in a large, geographically dense sample is an effective way to detect cryptic population genetic structure. The importance of SNPs in studies of population and wildlife genomics is rapidly increasing; this study adds to the growing body of recent literature that demonstrates the utility of SNPs ascertained from a model organism for evolutionary inference in closely related species.

Chapter 48 - Polycystic Kidney Disease

Many seabird breeding colonies have recovered from heavy anthropogenic disturbance after conservation actions. The widely distributed red‐tailed tropicbird, Phaethon rubricauda, was used as a model species to assess potential anthropogenic impacts on the genetic diversity of breeding colonies in the Pacific Ocean. Cytochrome c oxidase subunit I and control region sequences analyses were conducted across the range of the species in the Pacific Ocean. The study sites were at islands without human‐related disturbance (non‐impacted islands) and with human‐related disturbance (impacted islands). We hypothesized that (i) breeding colonies of the red‐tailed tropicbird on impacted islands have lower genetic diversity compared with colonies on non‐impacted islands, and (ii) breeding colonies of the red‐tailed tropicbird show significant fine and broad‐scale genetic structure across the Pacific Ocean. Bayesian skyline analyses were conducted to infer past changes in population sizes. Genetic diversity was similar between impacted and non‐impacted islands. There was significant broad‐scale genetic structure among colonies separated by over 6,000 km, but a lack of significant fine‐scale genetic structure within Australasia and Hawai'i, although a significant level of differentiation was found within Chile with ΦST analyses. Skyline analyses showed that effective population sizes remained relatively constant through time, but experienced either a slight decrease or the end of an expansion event through the last 1,000 years. These changes may be related to the arrival of humans on Pacific islands. Impacted islands may have received immigrants from other relatively close islands, buffering the loss of genetic diversity. However, it is also possible that colonies have retained ancestral variation or that a large effective population size coupled with a long generation time (13 years) has prevented the loss of genetic diversity in human‐impacted islands. Future research using higher‐resolution markers is needed to resolve the population genetic structure of the red‐tailed tropicbird in an ecological time‐scale.

We investigated the genetic diversity and genetic structure of southern California populations of the common intertidal fucoid seaweed Pelvetia fastigiata, (J. Ag.) De Toni by means of allozyme electrophoresis and estimates of genetic neighborhood area and size, which are the first for seaweeds. We predicted that P. fastigiata populations would exhibit relatively low genetic diversity and high genetic structure because the seaweed is monoecious and has limited dispersal of gametes and zygotes. This prediction was supported; genetic diversity indices were all low compared to other seaweeds studied, but high genetic structure was evident particularly within individual reefs. Geospatial statistical analyses (second-order analyses) revealed clustered distribution of glucose-6-phosphate isomerase (GPI) alleles at the scale of 1 to 6 m within three reefs. The rare alleles were distributed only at the landward third of the reefs. Genetic neighborhood area (2.3 m2) and size (133 individuals) were estimated from parent-offspring dispersal distributions of gametes and zygotes from attached thalli and also detached reproductive fragments, which contributed very little to the effective neighborhood size. The neighborhood size was in the small theoretical range in which genetic drift could be responsible for the within-reef genetic structure. This result was equivocal, because the stereotyped distribution of rare alleles on the tips of each reef was highly unlikely to be due to random events (6.9×10-24). These results emphasize (1) the importance of allele mapping in addition to spatial statistics to elucidate genetic structure, and (2) that interpretation of genetic-structure statistics as evidence for gene flow can be complicated, even when supported with independent estimates of gene flow, if data are lacking on selection and sporadic migration events. The emerging pattern of low levels of polymorphisms in brown seaweeds will limit the use of Wright's F-statistics and will require alternative, more direct techniques for the analysis of mechanisms responsible for population genetic structure.

Monitoring temporal changes in population genetic diversity and effective population size can provide vital information on future viability. The dusky gopher frog, Lithobates sevosus, is a critically endangered species found only in coastal Mississippi, with low genetic variability as a consequence of isolation and population size reduction. Conservation management practices have been implemented, but their efficacy has not been addressed. We genotyped individuals collected 1997–2014 to determine temporal trends in population genetic variation, structure, and effective size. Observed and expected heterozygosity and allelic richness revealed temporally stable, but low, levels of genetic variation. Positive levels of inbreeding were found in each year. There was weak genetic structure among years, which can be attributed to increased effects of genetic drift and inbreeding in small populations. L. sevosus exhibited an increase in effective population size, and currently has an estimated effective size of 33.0–58.6 individuals, which is approximately half the census size. This large ratio could possibly be explained by genetic compensation. We found that management practices have been effective at maintaining and improving effective size and genetic diversity, but that additional strategies need to be implemented to enhance viability of the species.

Landscape topography and the mobility of individuals will have fundamental impacts on a species' population structure, for example by enhancing or reducing gene flow and therefore influencing the effective size and genetic diversity of the population. However, social organization will also influence population genetic structure. For example, species that live and breed in cooperative groups may experience high levels of inbreeding and strong genetic drift. The western pebble-mound mouse (Pseudomys chapmani), which occupies a highly heterogeneous, semi-arid landscape in Australia, is an enigmatic social mammal that has the intriguing behaviour of working cooperatively in groups to build permanent pebble mounds above a subterranean burrow system. Here, we used both nuclear (microsatellite) and mitochondrial (mtDNA) markers to analyse the range-wide population structure of western pebble-mound mice sourced from multiple social groups. We observed high levels of genetic diversity at the broad scale, very weak genetic differentiation at a finer scale and low levels of inbreeding. Our genetic analyses suggest that the western pebble-mound mouse population is both panmictic and highly viable. We conclude that high genetic connectivity across the complex landscape is a consequence of the species' ability to permeate their environment, which may be enhanced by "boom-bust" population dynamics driven by the semi-arid climate. More broadly, our results highlight the importance of sampling strategies to infer social structure and demonstrate that sociality is an important component of population genetic structure.

American mink Neovison vison may be particularly vulnerable to toxicities of persistent contaminants such as PCBs because of their aquatic-based diet, position near the top of the food web, and small deme sizes. Furthermore, ranched mink are sensitive to reproductive toxicities of fish diets from PCB-polluted sites. The upper Hudson River is highly contaminated with PCBs and previous studies have shown elevated hepatic burdens of total and coplanar PCBs in mink collected near the river compared with those from more distant locales in New York and elsewhere. We hypothesized that bioaccumulation of PCBs in Hudson River mink has reduced their levels of genetic diversity or altered their genetic population structure. To address this, we conducted microsatellite DNA analysis on collections made in proximity to and from more distant locales in the Hudson River watershed, elsewhere in New York State, and at other sites in eastern North America including New Brunswick, four locales in Ontario, multiple drainages in Maine, and two ecoregions in Rhode Island. We did not find reduced genetic diversity at the individual or population levels in mink collected near (<6 km) to PCB hotspots in the Hudson River nor evidence of altered population structure. Consistent with their distribution in small localized and isolated demes, we did find significant genetic population structure among many mink collections in New York State and elsewhere. Depending on the analytical approach used, genetically distinct populations numbered between 16 when using STRUCTURE to 19-20 when using Exact G tests, F ST, or AMOVA analyses. Genetically distinct population units were found among major ecoregions and minor ecoregions in New York State, among different hydrologic subunits within the Hudson River watershed, among spatially separate locales in Ontario, and among most watersheds in Maine. However, despite this localization and potential heightened impact of stressors, genetic diversity and genetic population structure in mink does not seem to be affected by their bioaccumulation of high levels of PCBs of Hudson River origin.