Origins of the Domestic Dog and the Rich Potential for Gene Mapping

The unique breeding structure of the domestic dog makes canine genetics a useful tool to further the understanding of inherited diseases and gene function. Answers to the questions of when and where the dog was domesticated from the wolf are uncertain, but how the modern diversity of dog breeds was developed is documented. Breed development has resulted in many genetically isolated populations which are segregating for different alleles for disease and morphological and behavioral traits. Many genetic tools are available for dog research allowing investigation into the genetic basis of these phenotypes. Research into causes of diseases in dogs is relevant to humans and other species; comparative genomics is being used to transfer genetic information to them, including some studies on morphological and behavioral phenotypes. Because of the unique breed structure and well-maintained pedigrees, dogs represent a model organism containing a wealth of genetic information

Studies of the nature of chromosomal heterosis in Drosophila melanogaster.

From earlier studies it is known that the average disadvantage in fitness of homozygosity for either of the major autosomes of D. melanogaster is approximately 80%. The low relative fitness of the chromosomal homozygotes could be due to either of two causes, deleterious recessives (dominance) or heterozygote advantage (overdominance). Experimental evidence, most of which is for yield in plants, favours dominance as the cause of heterosis. In the light of this, the experiments presented here have been designed to test the dominance hypothesis

Narrow genetic basis for the Australian dingo confirmed through analysis of paternal ancestry

The dingo (Canis lupus dingo) is an iconic animal in the native culture of Australia, but archaeological and molecular records indicate a relatively recent history on the continent. Studies of mitochondrial DNA (mtDNA) imply that the current dingo population was founded by a small population of already tamed dogs from Southeast Asia. However, the maternal genetic data might give a unilateral picture, and the gene pool has yet to be screened for paternal ancestry. We sequenced 14,437 bp of the Y-chromosome (Y-chr) from two dingoes and one New Guinea Singing Dog (NGSD). This positioned dingo and NGSD within the domestic dog Y-chr phylogeny, and produced one haplotype not detected before. With this data, we characterized 47 male dingoes in 30 Y-chr single-nucleotide polymorphism sites using protease-mediated allele-specific extension technology. Only two haplotypes, H3 and H60, were found among the dingoes, at frequencies of 68.1 and 31.9 %, respectively, compared to 27 haplotypes previously established in the domestic dog. While H3 is common among Southeast Asian dogs, H60 was specifically found in dingoes and the NGSD, but was related to Southeast Asian dog Y-chr haplotypes. H3 and H60 were observed exclusively in the western and eastern parts of Australia, respectively, but had a common range in Southeast. Thus, the Y-chr diversity was very low, similar to previous observations for d-loop mtDNA. Overall genetic evidence suggests a very restricted introduction of the first dingoes into Australia, possibly from New Guinea. This study further confirms the dingo as an isolated feral dog. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10709-012-9658-5) contains supplementary material, which is available to authorized users

Genetic variation analysis of the Bali street dog using microsatellites

BACKGROUND: Approximately 800,000 primarily feral dogs live on the small island of Bali. To analyze the genetic diversity in this population, forty samples were collected at random from dogs in the Denpasar, Bali region and tested using 31 polymorphic microsatellites. Australian dingoes and 28 American Kennel Club breeds were compared to the Bali Street Dog (BSD) for allelic diversity, heterozygosities, F-statistics, G(ST )estimates, Nei's DA distance and phylogenetic relationships. RESULTS: The BSD proved to be the most heterogeneous, exhibiting 239 of the 366 total alleles observed across all groups and breeds and had an observed heterozygosity of 0.692. Thirteen private alleles were observed in the BSD with an additional three alleles observed only in the BSD and the Australian dingo. The BSD was related most closely to the Chow Chow with a F(ST )of 0.088 and also with high bootstrap support to the Australian dingo and Akita in the phylogenetic analysis. CONCLUSIONS: This preliminary study into the diversity and relationship of the BSD to other domestic and feral dog populations shows the BSD to be highly heterogeneous and related to populations of East Asian origin. These results indicate that a viable and diverse population of dogs existed on the island of Bali prior to its geographic isolation approximately 12,000 years ago and has been little influenced by domesticated European dogs since that time

Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study

Objective: GH and IGFs have mitogenic properties, causing speculation that GH treatment could increase risk of malignancy. While studies in GH-treated childhood cancer survivors have suggested a slight increase in second neoplasms, studies in GH-treated adults have been equivocal. Design: Incidence of de novo and second cancers was evaluated in 6840 GH-treated and 940 non GH-treated adult patients in the Hypopituitary Control and Complications Study pharmacoepidemiological database. Methods: Evident cancer cases were evaluated in the main analysis, with sensitivity analyses including probable and possible cancers. Standardized incidence ratios (SIRs) for cancers were calculated using Surveillance, Epidemiology and End Results for the USA and GLOBOCAN for all other countries. Results: During the mean follow-up of 3.7 years/GH-treated patient, 142 evident cancer cases were identified, giving an overall SIR of 0.88 (95% confidence interval (CI) 0.74-1.04); 95% CIs included the value of 1.0 for each country examined. The SIR for GH-treated patients from the USA (71 cases) was 0.94 (95% CI 0.73-1.18), and for non GH-treated patients from the USA (27 cases) was 1.16 (95% CI 0.76-1.69). For GH-treated patients from the USA aged < 35 years, the SIR (six cases) was 3.79 (1.39-8.26), with SIR not elevated for all other age categories; SIR for patients from the USA with childhood onset (CO) GH deficiency (GHD) was 2.74 (95% CI 1.18-5.41). The SIR for colorectal cancer in GH-treated patients (11 cases) was 0.60 (95% CI 0.30-1.08). Conclusions: With relatively short follow-up, the overall primary cancer risk in 6840 patients receiving GH as adults was not increased. Elevated SIRs were found for subgroups in the USA cohort defined by age < 35 years or CO GHD

A canine model of Cohen syndrome: Trapped Neutrophil Syndrome

<p>Abstract</p> <p>Background</p> <p>Trapped Neutrophil Syndrome (TNS) is a common autosomal recessive neutropenia in Border collie dogs.</p> <p>Results</p> <p>We used a candidate gene approach and linkage analysis to show that the causative gene for TNS is <it>VPS13B</it>. We chose <it>VPS13B </it>as a candidate because of similarities in clinical signs between TNS and Cohen syndrome, in human, such as neutropenia and a typical facial dysmorphism. Linkage analysis using microsatellites close to <it>VPS13B </it>showed positive linkage of the region to TNS. We sequenced each of the 63 exons of <it>VPS13B </it>in affected and control dogs and found that the causative mutation in Border collies is a 4 bp deletion in exon 19 of the largest transcript that results in premature truncation of the protein. Cohen syndrome patients present with mental retardation in 99% of cases, but learning disabilities featured in less than half of TNS affected dogs. It has been implied that loss of the alternate transcript of <it>VPS13B </it>in the human brain utilising an alternate exon, 28, may cause mental retardation. Mice cannot be used to test this hypothesis as they do not express the alternate exon. We show that dogs do express alternate transcripts in the brain utilising an alternate exon homologous to human exon 28.</p> <p>Conclusion</p> <p>Dogs can be used as a model organism to explore the function of the alternately spliced transcript of VPS13B in the brain. TNS in Border collies is the first animal model for Cohen syndrome and can be used to study the disease aetiology.</p

Genome sequencing highlights the dynamic early history of dogs

To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11-16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary

Mass balance of the Greenland Ice Sheet from 1992 to 2018

In recent decades, the Greenland Ice Sheet has been a major contributor to global sea-level rise1,2, and it is expected to be so in the future3. Although increases in glacier flow4–6 and surface melting7–9 have been driven by oceanic10–12 and atmospheric13,14 warming, the degree and trajectory of today’s imbalance remain uncertain. Here we compare and combine 26 individual satellite measurements of changes in the ice sheet’s volume, flow and gravitational potential to produce a reconciled estimate of its mass balance. Although the ice sheet was close to a state of balance in the 1990s, annual losses have risen since then, peaking at 335 ± 62 billion tonnes per year in 2011. In all, Greenland lost 3,800 ± 339 billion tonnes of ice between 1992 and 2018, causing the mean sea level to rise by 10.6 ± 0.9 millimetres. Using three regional climate models, we show that reduced surface mass balance has driven 1,971 ± 555 billion tonnes (52%) of the ice loss owing to increased meltwater runoff. The remaining 1,827 ± 538 billion tonnes (48%) of ice loss was due to increased glacier discharge, which rose from 41 ± 37 billion tonnes per year in the 1990s to 87 ± 25 billion tonnes per year since then. Between 2013 and 2017, the total rate of ice loss slowed to 217 ± 32 billion tonnes per year, on average, as atmospheric circulation favoured cooler conditions15 and as ocean temperatures fell at the terminus of Jakobshavn Isbræ16. Cumulative ice losses from Greenland as a whole have been close to the IPCC’s predicted rates for their high-end climate warming scenario17, which forecast an additional 50 to 120 millimetres of global sea-level rise by 2100 when compared to their central estimate