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

Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer (BC) has been well established, and tumor-infiltrating lymphocytes (TILs) have emerged as a predictive and prognostic biomarker for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer (TNBC) and HER2-positive breast cancer. How computational assessment of TILs can complement manual TIL-assessment in trial- and daily practices is currently debated and still unclear. Recent efforts to use machine learning (ML) for the automated evaluation of TILs show promising results. We review state-of-the-art approaches and identify pitfalls and challenges by studying the root cause of ML discordances in comparison to manual TILs quantification. We categorize our findings into four main topics; (i) technical slide issues, (ii) ML and image analysis aspects, (iii) data challenges, and (iv) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns, or design choices in the computational implementation. To aid the adoption of ML in TILs assessment, we provide an in-depth discussion of ML and image analysis including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial- and routine clinical management of patients with TNBC

Molecular Profiling of the Population Dynamics : Foundation and Expansion of an Archaic Domesticate

"An ‘exponential growth of science’ throughout modern history has been frequently boasted by numerous narcissistic accounts of ‘modern humanity.’ Nonetheless, ‘modern science’ seems to have overwhelmingly compromised on its original promises by fitting into an ‘industrial scheme.’ With this concern, ‘molecular phylogeographics with conservational ambitions’ would look an intact ground for research efforts in a ‘school of biotechnology.’ The dog (Canis familiaris) as an earliest domestic animal has a history of conflicts over its origins and dispersal. Having those disputes addressed, valuable knowledge could be acquired on the nature and dynamics of domestication, and of human societies particularly of pre-agricultural ages. We employed two most widely-used genealogical markers, the mitochondrial DNA (mtDNA) and the non-recombining portion of the Y-chromosome (NRY), to address dog demography. Through 582 bps of mtDNA Control Region, complemented with whole mitochondrial genomes, it was established that almost all maternal lineages of the domestic dog worldwide coalesce to a population of at least 51 and perhaps many more female wolves in Asia South of Yangtze River (ASY) approximately 16,000 years before present (BP). This was based on the presence of a maximal diversity in this area, a descending gradient of diversity outward it, and a ubiquitous population structure everywhere in the world. A closer examination of this portrait in Southwest Asia (SwAsia) and the Fertile Crescent (FC), a region which has supplied persuasive evidence on early presence of the domestic dog, retrieved the same information, with implications for backbreeding with the local wolf population. Meanwhile, analyses of mtDNA dispersal showed that dogs took the long way via land to Madagascar Island, and not together with humans via sea. By the other approach, the NRY data in 14,437 bps length supplemented the mtDNA in reporting the height of diversity from ASY with a founding population of at least 13 male wolves, but expectably produced lower inter-regional differentiation by diversity. Screening of NRY by a SNP assay in the dingoes of Australia Island as a population of feral dogs revealed restricted and similar dispersal patterns for sires and dams. Prospects of ancient, multilocus and whole genome assays with the emerging high-throughput technologies has still more to promise on finer elaborations of these issues."QC 20120529</p

African origin for Madagascan dogs revealed by mtDNA analysis

CITATION: Ardalan, A., et al. 2016. African origin for Madagascan dogs revealed by mtDNA analysis. Royal Society Open Science, 2: 140552, doi:10.1098/rsos.140552.The original publication is available at http://rsos.royalsocietypublishing.orgMadagascar was one of the last major land masses to be inhabited by humans. It was initially colonized by Austronesian speaking Indonesians 1500–2000 years ago, but subsequent migration from Africa has resulted in approximately equal genetic contributions from Indonesia and Africa, and the material culture has mainly African influences. The dog, along with the pig and the chicken, was part of the Austronesian Neolithic culture, and was furthermore the only domestic animal to accompany humans to every continent in ancient times. To illuminate Madagascan cultural origins and track the initial worldwide dispersal of dogs, we here investigated the ancestry of Madagascan dogs. We analysed mtDNA control region sequences in dogs from Madagascar (n=145) and compared it with that from potential ancestral populations in Island Southeast Asia (n=219) and sub-Saharan Africa (n=493). We found that 90% of the Madagascan dogs carried a haplotype that was also present in sub-Saharan Africa and that the remaining lineages could all be attributed to a likely origin in Africa. By contrast, only 26% of Madagascan dogs shared haplotypes with Indonesian dogs, and one haplotype typical for Austronesian dogs, carried by more than 40% of Indonesian and Polynesian dogs, was absent among the Madagascan dogs. Thus, in contrast to the human population, Madagascan dogs seem to trace their origin entirely from Africa. These results suggest that dogs were not brought to Madagascar by the initial Austronesian speaking colonizers on their transoceanic voyage, but were introduced at a later stage, together with human migration and cultural influence from Africa.http://rsos.royalsocietypublishing.org/content/2/5/140552#pagePublisher's versio

Complete Range of the Universal mtDNA Gene Pool and High Genetic Diversity in the Thai Dog Population

The dog population of Southern East Asia is unique in harboring virtually the full range of the universal mtDNA gene pool, and consequently, it has the highest genetic diversity worldwide. Despite this, limited research has been performed on dog genetics within this region. Here we present the first comprehensive study of a sub-region within Southern East Asia, analyzing 528 bp of mtDNA for 265 dogs from Thailand, in the context of dogs from across the Old World. We found that Thailand was the only region in the world that has the full range of the universal mtDNA gene pool, that is, all 10 sub-haplogroups. Consequently, the statistics for diversity are among the highest, especially in North Thailand, which had high values for haplotype diversity and the number of haplotypes, and the lowest proportion of individuals with a universal type-derived haplotype (UTd) among all regions. As previously observed, genetic diversity is distinctly lower outside Southern East Asia and it decreases following a cline to the lowest values in western Eurasia. Thus, the limited geographical region of Thailand harbors a distinctly higher genetic diversity than much larger regions in western Eurasia, for example, Southwest Asia and Europe which have only five and four of the 10 sub-haplogroups, respectively. Within Thailand, diversity statistics for all four sub-regions follow the general pattern of Southern East Asia, but North Thailand stands out with its high diversity compared to the other regions. These results show that a small part of Southern East Asia harbors the full range of the mtDNA gene pool, and they emphasize the exceptional genetic status of Southern East Asia. This indicates that today&rsquo;s dogs can trace a major part of their ancestry to Southern East Asia or closely situated regions, highlighting Thailand as a region of special interest. Considering the large genetic diversity found in Thailand and that many neighboring regions, e.g., Myanmar and Laos, have not been studied for dog genetics, it is possible that large parts of the dog gene pool remain undiscovered. It will be an important task for future studies to fill in these blanks on the phylogeographic map

Machine Learning Based Classification of Microsatellite Variation: An Effective Approach for Phylogeographic Characterization of Olive Populations.

Finding efficient analytical techniques is overwhelmingly turning into a bottleneck for the effectiveness of large biological data. Machine learning offers a novel and powerful tool to advance classification and modeling solutions in molecular biology. However, these methods have been less frequently used with empirical population genetics data. In this study, we developed a new combined approach of data analysis using microsatellite marker data from our previous studies of olive populations using machine learning algorithms. Herein, 267 olive accessions of various origins including 21 reference cultivars, 132 local ecotypes, and 37 wild olive specimens from the Iranian plateau, together with 77 of the most represented Mediterranean varieties were investigated using a finely selected panel of 11 microsatellite markers. We organized data in two '4-targeted' and '16-targeted' experiments. A strategy of assaying different machine based analyses (i.e. data cleaning, feature selection, and machine learning classification) was devised to identify the most informative loci and the most diagnostic alleles to represent the population and the geography of each olive accession. These analyses revealed microsatellite markers with the highest differentiating capacity and proved efficiency for our method of clustering olive accessions to reflect upon their regions of origin. A distinguished highlight of this study was the discovery of the best combination of markers for better differentiating of populations via machine learning models, which can be exploited to distinguish among other biological populations

Local origin or external input: modern horse origin in East Asia

Abstract Background Despite decades of research, the horse domestication scenario in East Asia remains poorly understood. Results The study identified 16 haplogroups with fine-scale phylogenetic resolution using mitochondrial genomes of 317 horse samples. The time to the most recent common ancestor of the 16 haplogroups ranges from [0.8–3.1] thousand years ago (KYA) to [7.9–27.1] KYA. With combined analyses of the mitochondrial control region for 35 extant Przewalski’s horses, 3544 modern and 203 ancient horses across the world, researchers provide evidence for that East Asian prevalent haplogroups Q and R were indigenously domesticated or they were involved in numerous distinct genetic components from wild horses in the southern part of East Asia. These events of haplotypes Q and R occurred during 4.7 to 16.3 KYA and 2.1 to 11.5 KYA, respectively. The diffusion of preponderant European haplogroups L from west to East Asia is consistent with the external gene input. Furthermore, genetic differences were detected between northern East Asia and southern East Asia cohorts by Principal Component Analysis, Analysis of Molecular Variance test, the χ2 test and phylogeographic analyses. Conclusions All results suggest a complex picture of horse domestication, as well as geographic pattern in East Asia. Both local origin and external input occurred in East Asia horse populations. And besides, there are at least two different domestication or hybridization centers in East Asia

An old dog and new tricks: Genetic analysis of a Tudor dog recovered from the Mary Rose wreck

© 2014 Elsevier Ireland Ltd. The Tudor warship the Mary Rose sank in the Solent waters between Portsmouth and the Isle of Wight on the 19th of July 1545, whilst engaging a French invasion fleet. The ship was rediscovered in 1971 and between 1979 and 1982 the entire contents of the ship were excavated resulting in the recovery of over 25,000 objects, including the skeleton of a small to medium sized dog referred to as the Mary Rose Dog (MRD). Here we report the extraction and analysis of both mitochondrial and genomic DNA from a tooth of this animal. Our results show that the MRD was a young male of a terrier type most closely related to modern Jack Russell Terriers with a light to dark brown coat colour. Interestingly, given the antiquity of the sample, the dog was heterozygotic for the SLC2A9 gene variant that leads to hyperuricosuria when found in modern homozygotic animals. These findings help shed light on a notable historical artefact from an important period in the development of modern dog breeds