Podcasts about haplotype

From the heart of the Mongolian steppe, to North China's loess plateaus; from the rugged edges of Northern India, to the hot sands of Syria and the Levant, to humid jungles in southeastern Asia, rocky islands off the coast of Japan, the high peaks of the Caucasus, Himalayas, Altai, Tien Shan and Carpathian Mountains, to the frozen rivers  in Rus' granting access to Eastern Europe, and everywhere in between.  Our series on the Mongol Empire has taken you across Eurasia, meeting all sorts of figures; the brutal Tamerlane, the indefatigable Sultan Baybars, the brave if shortsighted Jalal al-Din Mingburnu and his foolish father Muhammad Khwarezmshah; the cunning Jia Sidao, the silver-tongued Qiu Chuji, the thorough scholar Rashid al-Din, and travellers like John de Plano Carpini, William of Rubruck, and Ibn Battuta, to the exhausted but noble-hearted Yelü Chücai. And of course, the Mongols themselves: the powerful Öz Beğ, Khan of the Golden Horde; the thorough and pious convert Ghazan Il-Khan; the scheming Du'a of the Chagatais, the stout Qaidu Khan of the Ögedaids, to the Great Khans of the thirteenth century, the most powerful of men; Khubilai, whose hands scrambled for more until his body and empire failed his ambitions; his brother Möngke, whose steely determination sought to solidify the empire at all costs, no matter the bloodshed; Güyük, a reluctant and unfortunate man to ascend to the throne; his mother Törögene, whose fierce will forced her son to that same throne; Ögedai, a drunk who despite his failings built the infrastructure of the empire. And of course, Chinggis himself; once a scared boy in the steppes, turned into the greatest conqueror of them all. Today we end our journey with the Empire of the Great Khans, and reflect on the passage of the Chinggisids. I'm your host David, and this is Kings and Generals, Ages of Conquest.       Back in our first episode, we highlighted certain trends to look for over the course of this series. The first emphasized looking for the middle ground between the Mongols as inherently evil or good forces, but as people whose expansion was rooted in historical events and personages. The second was the struggles that came with the management of a world empire, and the need to rely on non-Mongolian subject peoples—Chinese, Central Asian Muslims, Persians, Turks and others. The third was the struggle for the purpose of the empire; should it be continued conquest, or consolidation and serving the needs of the imperial princes. This was the balance between the Khan and his central government, or the Chinggisid and military aristocrats. The fourth was the steady assimilation, particularly Turkification, of the Mongols outside of Mongolia, as Mongolian was replaced as the language of administration, legitimacy and finally, among the ruling family itself, even while retaining the Mongolian imperial ideology.        Regarding the first theme, we have sought to highlight in our many discussions of sources their often complicated, conflicting portrayals or events and persons. While authors like Ibn al-Athir, Nasawi and Juzjani had little good to say about the Mongols or Chinggis Khan, and fit well with the popular model the destructive brute, we've also looked at many sources which had more positive portrayals of the khans. Some of these are rather obvious, imperial-produced sources such as the Secret History of the Mongols, but even sources from outside the empire could give glowing reviews of Chinggis Khan. For instance, the fourteenth century English writer Geoffrey Chaucer, in the Squire's Tale of his famous Canterbury Tales, opens with the following lines:   At Tzarev in the land of Tartary There dwelt a king at war with Muscovy Which brought the death of many a doughty man This noble king was known as Cambuskan And in his time enjoyed such great renown That nowhere in that region up or down Was one so excellent in everything; Nothing he lacked belonging to a king.       Written at the same time as Toqtamish Khan of the Golden Horde was fighting for control of that Khanate, here Chaucher remembered Chinggis Khan not as a bloodthirsty barbarian, but as a monarch embodying all ideal qualities of kingship. Chaucer continues thusly;   As to the faith in which he had been born He kept such loyalties as he had sworn, Then he was powerful and wise and brave, Compassionate and just, and if he gave His word he kept it, being honourable, The same to all, benevolent, and stable As is a circle's centre; and in fight As emulous as any squire or knight. Young personable, fresh and fortunate, Maintaining such a kingliness of state There never was his match in mortal man, This noble king, this Tartar Cambuskan.        For writers in fourteenth century England, obviously distant from the Mongol Empire itself, it was not unbecoming to idealize the portrayal of Chinggis Khan. This is not to say that Chaucher's description is accurate, or necessarily reflects any actual qualities about the man or any of his descendants. But rather, it reflects historical perception. How an individual is perceived by contemporaries, history, and modern people often bears little resemblance to actual details of the individual.  Instead, people will contort an image for whatever use suits their current purposes, context and political climate. Thus, warlords from the late imperial, and post-Mongol world styled Chinggis' image to suit their needs. In Central Asia Chinggisid descent remained one of the most prestigious, and necessary, requirements for rulership up until the nineteenth century in some areas. This was problematic though with the spread of Islam, given that Chinggis Khan's actual life produced very few episodes to nicely accommodate an Islamic narrative. Certain Persian writings during the Ilkhanate sought to fix this by making Chinggis a Muslim in all but name. On the tomb of Tamerlane, an inscription likely added during the reign of his grandson Ulugh Beğ, makes Tamerlane a descendant of both the Prophet Muhammad and of Chinggis Khan. Later post-imperial authors had a more direct solution; simply making Chinggis Khan outright a Muslim. As the destruction of the conquests slipped further back in time, this became easier and easier to accomplish.    Religion was not the only aspect which can be molded, for Chinggis' very status as a Mongol becomes malleable in state efforts to construct national mythos, in both medieval and modern settings. Today, you can find countries where official propaganda, or influential theorists, incorporate Chinggis into the desired story of their nation-state. In China, there remains a significant Mongolian population, largely in what the Chinese call the Inner Mongolian Autonomous Region, the land south of the Gobi desert but north of the mountains which divide it from the North China plain. The Chinese government has taken to presenting China's non-Han peoples, Mongols among them, more or less as Chinese minority peoples and actively encourages their adoption of the state-language, Mandarin, and Han Chinese culture. In this view, the Mongol conquests are sometimes presented as a period of national reunification rather than foreign conquest. The efforts of Khubilai Khaan to legitimize the Yuan Dynasty based on Chinese dynastic legal precedent becomes the quote-on-quote “historical evidence,” that Chinggis Khan was actually Chinese, or that in fact, the Mongol conquerors were fully assimilated into the Chinese population and culture. The borders of the Yuan Dynasty served to justify later Chinese territorial claims in Inner Mongolia, Xinjiang, Manchuria, Tibet and Yunnan; places that were, before the Mongols, inconsistently in the Chinese sphere of influence, but since the conquests have often remained dominated by empires based in China. Not coincidentally, such narratives serve to support the narrative of 5,000 years of a continuous Chinese Empire, and remove the sting that may accompany the embarrassment of being conquered by perceived barbarians.    Likewise, various Turkic peoples, most notably Kazakhs, Tatars, and Anatolian Turks, have sought to claim Chinggis as their own, and there are even groups in Korea and Japan that will argue that Chinggis was actually one of theirs. The Japanese version has Chinggis as the Samurai Minamoto no Yoshitsune, who faked his death and fled Japan for the steppe! Khubilai's later invasions of Japan again become not foreign assaults, but attempts at national reunification or the efforts by Yoshitsune's descendants to return home. And of course, fringe groups even in Europe and Russia which, refusing to believe a barbarian horseman could conquer such great states, insist that Chinggis was actually a red-haired, green-eyed man of European ancestry. Such claims often include vague references to the mummies of the Tarim Basin, who bore some features associated with Caucasian populations. The fact that these mummies pre-date Chinggis by millenia is often conveniently left out. All of these people care much more about ethnic categorization than Chinggis himself likely ever did.        Just as religion or ethnicity can be forced to fit certain agendas, so too can portrayal as barbarian or saviour. In Mongolia today, Chinggis Khan's unification of the Mongols, his introduction of a writing system, religious tolerance, laws and stability are most heavily emphasized. For building a post-soviet national identity, obviously these are useful attributes to appeal to for the desired national character. But the Mongolian governmet also tends to gloss over the aspects less appreciated in the twenty-first century: namely, the destruction of people and property on a massive scale, mass-rapes, towers of skulls and wars of conquest. The fact that Mongolia's two neighbours, Russia and China, suffered particularly under Mongol onslaughts, also avoids some diplomatic hurdles to step past these military aspects. For most of the twentieth century during Mongolia's years as a Soviet satellite state, Chinggis was largely pushed aside, framed as a feudal lord. Instead, Mongolia's hero of the 1921 socialist revolution, Damdin Sükhbaatar, became the preferred national icon. After Mongolia was democratized in the 1990s after the fall of the USSR, Chinggis Khan has seen a massive resurgence in popularity. Today, Chinggis and Sükhbaatar remain national icons, with monuments to both throughout the country. Outside Mongolia's parliament, the main square has changed names from Sükhbaatar to Chinggis Square, and since back to Sükhbaatar square. An equestrian statue to Sükhbaatar sits in the middle of that square. More than a few foreign observers had mistakenly called this a statue of Chinggis. In fact, only a few metres away from the equestrian statue of Sükhbaatar sits a massive Chinggis Khan on a throne flanked by his generals, at the top of the steps leading into Mongolia's parliament. In a way it is metaphorical. No matter how prominent any later hero of Mongolia may be, he will always stand in the shadow of Chinggis Khan.  And that's not even mentioning the 40 metre tall silver monstrosity about 50 kilometres outside of Ulaanbaatar. Speaking of state narratives, much of the cost for this statue was covered by the company owned by Khaltmaagin Battulga, a former professional sambo wrestler who from 2017-2021 served as the fifth President of Mongolia.       Outside of Mongolia though, Chinggis and the Mongol Empire remain a top-point of reference to paint someone in the most unfavourable light. One of the highest level cases of recent years was when the President of Iraq, the late Saddam Hussein, compared former US President George W. Bush to Hülegü, Chinggis' grandson and conqueror of Baghdad. The American bombing and capture of Baghdad, and ensuing tragedies that Iraq as suffered in the aftermath of the campaign, have only solidified the connection for a number of Muslims.  Meanwhile Russian television and education tend to present the Mongols in a style comparable to Zack Snyder's film 300, such as the 2017 Russian film Легенда о Коловрате [Legenda O Kolovrate], also known as Furious. Like the Spartans in the film or Frank Miller's graphic novel, the Rus' soldiers are presented as formidable warriors fighting monstrous, untrained hordes from the east. Only through sheer numbers or trickery do the disgusting Orientals overcome the pasty-white heroes of the story— though few of the heroes in the Russian films have Scottish accents. Russia has turned the so-called Tatar Yoke into a catch-all to explain any perceived deficiencies compared to western Europe, from government absolutism to alcoholism. Not only the Russians have employed the comparison: “scratch a Russian and you'll find a Tatar,” Napoleon Bonaparte is supposed to have quipped. And in 2018 the Wall Street Journal released a particularly poorly written article, which compared the political machinations of current president Vladimir Putin as “Russia's turn to its Asian past,” accompanied by vague comparisons to the Mongols and an awful portrait of Putin drawn in Mongolian armour. In contrast, the Russian Defence Minister, at the time of writing, is Sergei Shoigu, a fellow of Tuvan descent who is alleged to enjoy comparisons of himself to Sübe'edei, the great Mongol general popularly, though inaccurately, portrayed as a Tuvan. The 2022 Russian invasion of Ukraine, essentially a good old-fashioned war of conquests accompanied by war crimes and destruction of cities, has also earned many comparisons to the Mongol conquests by many online commentators. Though unlike the Russians, the Mongols actually took Kyiv.   Somewhat surprisingly, most cinematic portrayals of Chinggis himself lean towards sympathetic or heroic. One of the most recent is a 2018 Chinese film entitled Genghis Khan in English, which features a slim Chinese model in the titular role, and one of his few depictions without any facial hair. In that film he battles a bunch of skeletons and monsters, and it could be best described as “not very good,” as our series researcher can, unfortunately, attest. One popular portrayal is the 2007 film Mongol, directed by Sergei Bodrov and starring a Japanese actor in the role of Chinggis. That actor, by the way, went on to play one of Thor's buddies in the Marvel movies.  Here, Chinggis is a quiet, rather thoughtful figure, in a film which emphasizes the brutal childhood he suffered from. Another sympathetic portrayal, and one perhaps the most popular in Mongolia, is the 2004 Inner Mongolian series where Ba Sen, an actor who claims descent from Chagatai and appeared in the previously two mentioned films, plays the role of Chinggis.       Hollywood does not tend to portray Chinggis Khan or the Mongols in films at all, but when it does, it really goes for a swing and a miss. Bill and Ted's Excellent Adventure has Chinggis essentially only a step above a cave-man in that film. Other Hollywood endeavours are infamous for having non-Asian actors in the role, such as Egyptian-born Omar Shariff in 1965's Genghis Khan, Marvin Miller in 1951's The Golden Horde and the most infamous of them all, the cowboy John Wayne in 1956's The Conqueror. That film's theatrical release poster bears the tasteful tagline of, “I am Temujin…barbarian… I fight! I love! I conquer… like a Barbarian!” The film was also produced by Howard Hughes, founder of Playboy Magazine, and was filmed near a nuclear testing site.  As you may suspect, that film bears as much resemblance to the historical events as an opium-induced fever dream.        The appearance and depiction of Chinggis and his successors varies wildly. The internet today loves the stories of Chinggis being the ancestor of millions of people, and killing so many people that it changed the earth's climate. The articles that made both of these claims though, rested on shaky evidence. In the first, which we dedicated an entire episode of this podcast too, the study claimed that high rates of a certain haplotype among the Hazara of Afghanistan demonstrated that Chinggis himself bore that haplotype, and Chinggis was extrapolated to be the ancestor of other peoples bearing such a haplotype. But the historical sources indicate Chinggis and his immediate descendants spent little time in Afghanistan, and the associated Haplotype was probably one associated with various populations leaving Mongolia over centuries, rather than specifically Chinggis himself.  Likewise, the study which spawned the claim that the Mongols killed enough people to cool the climate, firstly did not make that claim itself, but moreso incorrectly made the Mongol conquests last from 1206 to 1380, and presented it as an almost two-century period of population decline brought on by Mongolian campaigns; despite the fact that the major destructive Mongolian military campaigns largely halted after 1279. While campaigns continued after that, they were never on the level of the great-campaigns of conquest. Thus it's irresponsible to claim that any atmospheric carbon loss over the fourteenth century was brought on by continued Mongol military efforts.       What these two popular descriptions lend themselves to, is one of extremes. The internet loves extremes of anything. For instance, since 1999 the Internet has always sought to outdo itself in declaring the latest Star Wars product to actually be the worst thing ever made. And the Mongol Empire, as history's largest contiguous land-empire, responsible for immense destruction and long-ranging campaigns and forced migrations, can easily slot in this ‘extreme manner.' A “top-ten” list where the author writes about how the Mongols were the most extreme and destructive and badass thing ever, repeating the same 10 facts, probably gets released on the internet every other month. Just as national-myth makers in Ulaanbaatar, Beijing and Moscow set how to portray the Mongol Empire in the way most suited to them, so too does the internet and its writers choose an aspect of the empire to emphasis; be it religious tolerance, free-trade, brutality, multi-culturalism, Islam, clash of civilizations, human impact on climate, the territorial expanse of a certain country or its national identity, or whatever argument the author hopes to make.        The Mongol Empire though remains in the past, and should be treated, and learned about, as such.  The events which led to the rise, expansion and fall of the Mongol Empire do not fit into nice, sweeping modern narratives, but their own historical context and situation. The Mongol Empire was not predetermined to ever expand out of Mongolia, or to break apart in 1260; had Chinggis Khan been struck by an arrow outside the walls of Zhongdu, or Möngke lived another ten years, in both cases the empire, and indeed the world, would look dramatically different. History is not the things which ought to be or needed to happen or were supposed to happen; it is the things that did happen, and those things did not occur simply for the purposes of the modern world to exist. A million choices by hundreds of millions of individuals, affected by climate and geography with a healthy dose of luck and happenstance, resulted in the world as we know it. Reading backwards from the present to understand the course of the Mongol Empire, and attempting to make it fit into the political narratives we like today, only does a disservice to history. It should be seen not as a virtuous force bringing continental peace justified by easier trade, nor as a demonic horde, but as an event within human history, in which real humans took part, where great tragedy occured in the pursuit of empire.     History is not just written by the victor of the actual battles; as we've detailed across this series, we have no shortage of historical sources on the Mongol Empire; imperial approved sources, sources by travellers passing through the empire, to sources written by the peoples the Mongols crushed. Instead, the history learned in schools and passed down through historical memory and media is built on top of preferred state narratives, those made today and in the past.   Our series on the Mongol Empire concludes next week with a final afterward on Mongolia after 1368, so be sure to subscribe to the Kings and Generals podcast to follow. If you enjoyed this was want to help us keep bringing you great content, then consider supporting us on patreon at www.patreon.com/kingsandgenerals. This episode was researched and written by our series historian, Jack Wilson. I'm your host David, and we'll catch you on the next one. 

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.09.374140v1?rss=1 Authors: Klasberg, S., Schmidt, A. H., Lange, V., Schöfl, G. Abstract: Background: High resolution HLA genotyping of donors and recipients is a crucially important prerequisite for haematopoetic stem-cell transplantation and relies heavily on the quality and completeness of immunogenetic reference sequence databases of allelic variation. Results: Here, we report on DR2S, an R package that leverages the strengths of two sequencing technologies - the accuracy of next-generation sequencing with the read length of third-generation sequencing technologies like PacBio's SMRT sequencing or ONT's nanopore sequencing - to reconstruct fully-phased high-quality full-length haplotype sequences. Although optimised for HLA and KIR genes, DR2S is applicable to all loci with known reference sequences provided that full-length sequencing data is available for analysis. In addition, DR2S integrates supporting tools for easy visualisation and quality control of the reconstructed haplotype to ensure suitability for submission to public allele databases. Conclusions: DR2S is a largely automated workflow designed to create high-quality fully-phased reference allele sequences for highly polymorphic gene regions such as HLA or KIR. It has been used by biologists to successfully characterise and submit more than 500 HLA alleles and more than 500 KIR alleles to the IPD-IMGT/HLA and IPD-KIR databases. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.06.371799v1?rss=1 Authors: Shaw, J., Yu, Y. W. Abstract: Resolving haplotypes in polyploid genomes using phase information from sequencing reads is an important and challenging problem. We introduce two new mathematical formulations of polyploid haplotype phasing: (1) the min-sum max tree partition (MSMTP) problem, which is a more flexible graphical metric compared to the standard minimum error correction (MEC) model in the polyploid setting, and (2) the uniform probabilistic error minimization (UPEM) model, which is a probabilistic generalization of the MEC model. We incorporate both formulations into a long-read based polyploid haplotype phasing method called flopp. We show that flopp compares favorably to state-of-the-art algorithms -- up to 30 times faster with 2 times fewer switch errors on 6x ploidy simulated data. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.06.370858v1?rss=1 Authors: Popitsch, N., Preuner, S., Lion, T. Abstract: Clinical decision making is increasingly guided by accurate and recurrent determination of presence and frequency of (somatic) variants and their haplotype through panel sequencing of disease-relevant genomic regions. Haplotype calling (phasing), however, is difficult and error prone unless variants are located on the same read which limits the ability of short-read sequencing to detect, e.g., co-occurrence of drug-resistance variants. Long-read panel sequencing enables direct phasing of amplicon variants besides having multiple other benefits, however, high error rates of current technologies prevented their applicability in the past. We have developed nanopanel2 (np2), a variant caller for Nanopore panel sequencing data. Np2 works directly on base-called FAST5 files and uses allele probability distributions and several other filters to robustly separate true from false positive calls. It effectively calls SNVs and INDELs with variant allele frequencies (VAF) as low as 1% and 5% respectively and produces only few low-frequency false-positive calls. Haplotype compositions are then determined by direct phasing. Np2 is the first somatic variant caller for Nanopore data, enabling accurate, fast (turnaround

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.23.349407v1?rss=1 Authors: Wu, C.-Y., Lau, B. T., Kim, H., Sathe, A., Grimes, S. M., Ji, H. P., Zhang, N. R. Abstract: Cancer progression is driven by both somatic copy number aberrations (CNAs) and chromatin remodeling, yet little is known about the interplay between these two classes of events in shaping the clonal diversity of cancers. We present Alleloscope, a method for allele-specific copy number estimation that can be applied to single cell DNA and ATAC sequencing data, either separately or in combination. This approach allows for integrative multi-omic analysis of allele-specific copy number and chromatin accessibility on the same cell. On scDNA-seq data from gastric, colorectal, and breast cancer samples, with extensive validation using matched linked-read sequencing, Alleloscope finds pervasive occurrence of highly complex, multi-allelic copy number aberrations, where cells that carry varying allelic configurations adding to the same total copy number co-evolve within a tumor. The contributions of such allele-specific events to intratumor heterogeneity have been under-reported and under-studied due to the lack of methods for their detection. On scATAC-seq from two basal cell carcinoma samples and a gastric cancer cell line, Alleloscope detects multi-allelic copy number events and copy neutral loss-of-heterozygosity, enabling the dissection of the contributions of chromosomal instability and chromatin remodeling in tumor evolution. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.21.348607v1?rss=1 Authors: Olyaee, M. H., Khanteymoori, A. Abstract: Evolution of human genetics is one of the most interesting areas for researchers. Determination of Haplotypes not only makes valuable information for this purpose but also performs a major role in investigating the probable relation between diseases and genomes. Determining haplotypes by experimental methods is a time-consuming and expensive task. Recent progress in high throughput sequencing allows researchers to use computational methods for this purpose. Although, several algorithms have been proposed but they are less accurate when the error rate of input fragments increases. In this paper, first, a fuzzy conflict graph is constructed based on the similarities of all input fragments and next, the cluster centers are used as initial centers by fuzzy c-means (FCM) algorithm. The proposed method has been tested on several real datasets and compared with some current methods. The comparison with the existing approaches shows that our method can be a complementary role among the others. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.29.318907v1?rss=1 Authors: Olyaee, M. H., Khanteymoori, A., Khalifeh, K. Abstract: Decreasing the cost of high-throughput DNA sequencing technologies, provides a huge amount of data that enables researchers to determine haplotypes for diploid and polyploid organisms. Although various methods have been developed to reconstruct haplotypes in diploid form, their accuracy is still a challenging task. Also, most of the current methods cannot be applied to polyploid form. In this paper, an iterative method is proposed, which employs hypergraph to reconstruct haplotype. The proposed method by utilizing chaotic viewpoint can enhance the obtained haplotypes. For this purpose, a haplotype set was randomly generated as an initial estimate, and its consistency with the input fragments was described by constructing a weighted hypergraph. Partitioning the hypergraph specifies those positions in the haplotype set that need to be corrected. This procedure is repeated until no further improvement could be achieved. Each element of the finalized haplotype set is mapped to a line by chaos game representation, and a coordinate series is defined based on the position of mapped points. Then, some positions with low qualities can be assessed by applying a local projection. Experimental results on both simulated and real datasets demonstrate that this method outperforms most other approaches, and is promising to perform the haplotype assembly. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.29.318642v1?rss=1 Authors: Ke, Z., Vikalo, H. Abstract: Haplotype assembly and viral quasispecies reconstruction are challenging tasks concerned with analysis of genomic mixtures using sequencing data. High-throughput sequencing technologies generate enormous amounts of short fragments (reads) which essentially oversample components of a mixture; the representation redundancy enables reconstruction of the components (haplotypes, viral strains). The reconstruction problem, known to be NP-hard, boils down to grouping together reads originating from the same component in a mixture. Existing methods struggle to solve this problem with required level of accuracy and low runtimes; the problem is becoming increasingly more challenging as the number and length of the components increase. This paper proposes a read clustering method based on a convolutional auto-encoder designed to first project sequenced fragments to a low-dimensional space and then estimate the probability of the read origin using learned embedded features. The components are reconstructed by finding consensus sequences that agglomerate reads from the same origin. Mini-batch stochastic gradient descent and dimension reduction of reads allow the proposed method to efficiently deal with massive numbers of long reads. Experiments on simulated, semi-experimental and experimental data demonstrate the ability of the proposed method to accurately reconstruct haplotypes and viral quasispecies, often demonstrating superior performance compared to state-of-the-art methods. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.26.267617v1?rss=1 Authors: Karkar, S. I., Dandine-Roulland, C. I., Mangin, J.-F., Le Guen, Y., Philippe, C., Deleuze, J.-F., Pierre-Jean, M., Le Floch, E., Frouin, V. Abstract: Neuroimaging-genetics cohorts gather two types of data: brain imaging and genetic data. They allow the discovery of associations between genetic variants and brain imaging features. They are invaluable resources to study the influence of genetics and environment in the brain features variance observed in normal and pathological populations. This study presents a genome wide haplotype analysis for 123 brain sulcus opening value (a measure of sulcal width) across the whole brain that include 16,304 subjects from UK Biobank. Using genetic maps, we defined 119,548 blocks of low recombination rate distributed along the 22 autosomal chromosomes and analyzed 1,051,316 haplotypes. To test associations between haplotypes and complex traits, we designed three statistical approaches. Two of them use a model that includes all the haplotypes for a single block, while the last approach considers one model by haplotype. All the statistics produced were assessed as rigorously as possible. Thanks to the rich imaging dataset at hand, we used resampling techniques to assess False Positive Rate for each statistical approach in a genome-wide and brain-wide context. The results on real data show that genome-wide haplotype analyses are more sensitive than single- SNP approach and account for local complex Linkage Disequilibrium (LD) structure, which makes genome-wide haplotype analysis an interesting and statistically sound alternative to the single-SNP counterpart. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.07.242305v1?rss=1 Authors: Roe, D., Vierra-Green, C., Pyo, C.-W., Geraghty, D. E., Spellman, S. R., Maiers, M., Kuang, R. Abstract: Human chromosome 19q13.4 contains genes encoding killer-cell immunoglobulin-like receptors (KIR). Reported haplotype lengths range from 67 to 269 kilobases and contain 4 to 18 genes. The region has certain properties such as single nucleotide variation, structural variation, homology, and repetitive elements that make it hard to align accurately beyond single gene alleles. To the best of our knowledge, a multiple sequence alignment of KIR haplotypes has never been published or presented. Such an alignment would be useful to precisely define KIR haplotypes and loci, provide context for assigning alleles (especially fusion alleles) to genes, infer evolutionary history, impute alleles, interpret and predict co-expression, and generate markers. In order to extend the framework of KIR haplotype sequences in the human genome reference, 27 new sequences were generated including 24 haplotypes from 12 individuals of African American ancestry that were selected for genotypic diversity and novelty to the reference, to bring the total to 68 full length genomic KIR haplotype sequences. We leveraged these data and tools from our long-read KIR haplotype assembly algorithm to define and align KIR haplotypes at

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.23.206391v1?rss=1 Authors: Al Bkhetan, Z., Chana, G., Soon Ong, C., Goudey, B., Kotagiri, R. Abstract: Motivation: The high accuracy of current haplotype phasing tools has enabled the interrogation of haplotype (or phase) information more widely in genetic investigations. Including such information in eQTL analysis complements SNP-based approaches as it has the potential to detect associations that may otherwise be missed. Results: We have developed a haplotype-based eQTL approach called eQTLHap to investigate associations between gene expression and haplotype blocks. Using simulations, we demonstrate that eQTLHap significantly outperforms typical SNP-based eQTL methods when the causal genetic architecture involves multiple SNPs. We show that phasing errors slightly impact the sensitivity of the proposed method (< 4%). Finally, the application of eQTLHap to real GEUVADIS and GTEx datasets finds 22 associations that replicated in larger studies or other tissues and could not be detected using a single-SNP approach. Availability: https://github.com/ziadbkh/eQTLHap Copy rights belong to original authors. Visit the link for more info

Long read sequencing technologies, such as Oxford Nanopore and PacBio, produce reads from thousands to a million base pairs in length, at the cost of the increased error rate. Trevor Pesout describes how he and his colleagues leverage long reads for simultaneous variant calling/genotyping and phasing. This is possible thanks to a clever use of a hidden Markov model, and two different algorithms based on this model are now implemented in the MarginPhase and WhatsHap tools. Links: Preprint: Haplotype-aware genotyping from noisy long reads (Jana Ebler, Marina Haukness, Trevor Pesout, Tobias Marschall, Benedict Paten)

We're continuing our discussion with Australian researcher, Dr. Simon Southerton. In this next episode, we're going to dig into the science deeper.  What is the Cohen Haplotype? https://youtu.be/Unyz4TXsb-s GT:  I know the Cohen haplotype is this genetic marker... We'll also talk about the Lemba Tribe. Simon:  All the Cohen is, is a particular Y-Chromosome which was present in the Lemba Tribe.  Now this is a tribe, they look African.  They are in Zimbabwe,[1] which is what—is that its current name?  Yes, I think that's its current name.  They had oral traditions that were Jewish.  They built very significant stone-walled cities, but most scholars rejected the fact that they were Jewish. It's not uncommon for native people all around the world to claim that they have got Jewish ancestry.  The Polynesians loved the fact that they think they are Jewish, because it ties them into the sort of Christian world that they like.  Anyway, it was rejected, and then they did the DNA work and they found that they have got a Semitic Y-Chromosome, in particular this Y-Chromosome which seems particularly common in the males of the priestly class, the Jewish priestly class.  So, it just confirmed conclusively that there was Jewish DNA that arrived down there. How is that helpful for looking for Book of Mormon DNA in the Americas? Simon: Yes, it is a clear case of how DNA, even though it is a fairly small incursion of DNA, they have been able to track it. GT:  Would you expect to find something similar in the Americas if that were the case? Simon:  I didn't expect to see every single Native American being a Jew, having Jewish DNA. I thought at least there had to be something.  I don't know what that percentage is, but we're down now to nothing.  Fifteen and a half thousand Native Americans have been tested, their mitochondrial DNA tested.  It's all Asian with a smattering of African, there is quite a lot of African DNA. Simon will talk about some of the newer DNA testing done on Native Americans, and why it doesn't bode well for those searching for Middle Eastern DNA here. Don't forget to check out our previous conversation with Simon, as well as Dr. Ugo Perego's discussion on the Lemba Tribe.  Check out our conversation….. Cohen Haplotype is found among Jews. Is it found in Native Americans? What is the Lemba Tribe? [paypal-donation] [1] Some Lemba live in South Africa also.  

Researchers have developed approaches for the noninvasive prenatal testing of single gene diseases.

Hosts: Nels Elde and Vincent Racaniello Nels visits Vincent in the MicrobeTV studio in New York and talks about how key genes of the Homo sapiens innate immune response were acquired from Neanderthals.   Links for this episode Introgressed Neanderthal haplotype at OAS locus (biorXiv) Genetic time travel (Genetics) Genetic history of Ice Age Europe (Nature) Letters read on TWiEVO 8 Science Picks Nels - DNA Clues to our Inner Neanderthal Vincent - Blockhead Music on TWiEVO is performed by Trampled by Turtles Send your evolution questions and comments to twievo@microbe.tv Become a patron of TWiEVO

Background Non-coding single nucleotide polymorphisms within the nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4) are robustly associated with various neurological and behavioral phenotypes including schizophrenia, cognition and smoking. The most commonly associated polymorphisms are located in exon 5 and segregate as part of a haplotype. So far it is unknown if this haplotype is indeed functional, or if the observed associations are an indirect effect caused by linkage disequilibrium with not yet identified adjacent functional variants. We therefore analyzed the functional relevance of the exon 5 haplotype alleles. Results Using voltage clamp experiments we were able to show that the CHRNA4 haplotype alleles differ with respect to their functional effects on receptor sensitivity including reversal of receptor sensitivity between low and high acetylcholine concentrations. The results indicate that underlying mechanisms might include differences in codon usage bias and changes in mRNA stability. Conclusions Our data demonstrate that the complementary alleles of the CHRNA4 exon 5 haplotype are functionally relevant, and might therefore be causative for the above mentioned associations.

Durbin, R (Welcome Trust Sanger Institute, Cambridge, UK) Tuesday 25 March 2014, 13:45-14:45

Tuesday, July 23, 2013 - 3:30 pm PST/6:30 pm EST Our incredible special guest tonight is Dr. Alicia Semaka, a Postdoctoral Fellow at the University of British Columbia. She received her MSc in Genetic Counseling in 2005 and her PhD in Medical Genetics under the supervision of Dr. Michael Hayden at the Centre for Molecular Medicine & Therapeutics in 2012. Her doctoral research focused on intermediate alleles for Huntington disease. Using a unique, multidisciplinary methodology that combined molecular and qualitative techniques, she generated new data on the frequency, haplotype, and CAG repeat instability of intermediate alleles and explored patient understanding and genetic counseling practices regarding intermediate allele predictive test results. Her research findings fill a significant gap in our knowledge on intermediate alleles and have important implications for predictive testing.  We will be discussing an overview of her research relating to implications for genetic counseling/predictive testing and the HD community and background information on intermediate alleles, CAG size range, repeat instability and factors that influence instability. Also topic for discussion, two family history case studies.

Background: The aims were to analyze two novel NOD2 variants (rs2066843 and rs2076756) in a large cohort of patients with inflammatory bowel disease and to elucidate phenotypic consequences. Methodology/Principal Findings: Genomic DNA from 2700 Caucasians including 812 patients with Crohn's disease (CD), 442 patients with ulcerative colitis (UC), and 1446 healthy controls was analyzed for the NOD2 SNPs rs2066843 and rs2076756 and the three main CD-associated NOD2 variants p.Arg702Trp (rs2066844), p.Gly908Arg (rs2066847), and p.Leu1007fsX1008 (rs2066847). Haplotype and genotype-phenotype analyses were performed. The SNPs rs2066843 (p = 3.01×10−5, OR 1.48, [95% CI 1.23-1.78]) and rs2076756 (p = 4.01×10−6; OR 1.54, [95% CI 1.28-1.86]) were significantly associated with CD but not with UC susceptibility. Haplotype analysis revealed a number of significant associations with CD susceptibility with omnibus p values

Background: We investigated the influence of genotyping errors on the type I error rate and empirical power of two haplotype based association methods applied to candidate regions. We compared the performance of the Mantel Statistic Using Haplotype Sharing and the haplotype frequency based score test with that of the Armitage trend test. Our study is based on 1000 replication of simulated case-control data settings with 500 cases and 500 controls, respectively. One of the examined markers was set to be the disease locus with a simulated odds ratio of 3. Differential and non-differential genotyping errors were introduced following a misclassification model with varying mean error rates per locus in the range of 0.2% to 15.6%. Results: We found that the type I error rate of all three test statistics hold the nominal significance level in the presence of nondifferential genotyping errors and low error rates. For high and differential error rates, the type I error rate of all three test statistics was inflated, even when genetic markers not in Hardy-Weinberg Equilibrium were removed. The empirical power of all three association test statistics remained high at around 89% to 94% when genotyping error rates were low, but decreased to 48% to 80% for high and nondifferential genotyping error rates. Conclusion: Currently realistic genotyping error rates for candidate gene analysis (mean error rate per locus of 0.2%) pose no significant problem for the type I error rate as well as the power of all three investigated test statistics.

The outcome of Genome-Wide Association Studies (GWAS) has challenged the field of blood pressure (BP) genetics as previous candidate genes have not been among the top loci in these scans. We used Affymetrix 500K genotyping data of KORA S3 cohort (n = 1,644; Southern-Germany) to address (i) SNP coverage in 160 BP candidate genes; (ii) the evidence for associations with BP traits in genome-wide and replication data, and haplotype analysis. In total, 160 gene regions (genic region+/-10 kb) covered 2,411 SNPs across 11.4 Mb. Marker densities in genes varied from 0 (n = 11) to 0.6 SNPs/kb. On average 52.5% of the HAPMAP SNPs per gene were captured. No evidence for association with BP was obtained for 1,449 tested SNPs. Considerable associations (P50% of HAPMAP SNPs were tagged. In general, genes with higher marker density (>0.2 SNPs/kb) revealed a better chance to reach close to significance associations. Although, none of the detected P-values remained significant after Bonferroni correction (P

Labarre, A (Libre de Bruxelles) Friday 21 December 2007, 11:30-11:50 PLGw03 - Future Directions in Phylogenetic Methods and Models

Background: ADAM33, the first asthma candidate gene identified by positional cloning, may be associated with childhood asthma, lung function decline and bronchial hyperresponsiveness. However, replication results have been inconclusive in smaller previous study populations probably due to inconsistencies in asthma phenotypes or yet unknown environmental influences. Thus, we tried to further elucidate the role of ADAM33 polymorphisms ( SNPs) in a genetic analysis of German case control and longitudinal populations. Methods: Using MALDI-TOF, ten ADAM33 SNPs were genotyped in 1,872 children from the International Study of Asthma and Allergy in Childhood (ISAAC II) in a case control setting and further 824 children from the longitudinal cohort Multicentre Study of Allergy (MAS). In both populations the effects of single SNPs and haplotypes were studied and a gene environment analysis with passive smoke exposure was performed using SAS/ Genetics. Results: No single SNP showed a significant association with doctor's diagnosis of asthma. A trend for somewhat more profound effects of ADAM33 SNPs was observed in individuals with asthma and BHR. Haplotype analyses suggested a minor effect of the ADAM33 haplotype H4 on asthma ( p = 0.033) but not on BHR. Associations with non atopic asthma and baseline lung function were identified but no interaction with passive smoke exposure could be detected. Conclusion: The originally reported association between ADAM33 polymorphisms and asthma and BHR could not be confirmed. However, our data may suggest a complex role of ADAM33 polymorphisms in asthma ethiology, especially in non atopic asthma.

Sun, 1 Jan 1989 12:00:00 +0100 http://epub.ub.uni-muenchen.de/3073/ http://epub.ub.uni-muenchen.de/3073/1/033.pdf Ragoussis, Jiannis; Bloemer, Katharina; Pohla, Heike; Messer, Gerald; Weiß, Elisabeth; Ziegler, Andreas Ragoussis, Jiannis; Bloemer, Katharina; Pohla, Heike; Messer, Gerald; Weiß, Elisabeth und Ziegler, Andreas (1989): A Physical Map Including a New Class I Gene (cda12) of the Human Major Histocompatibility Complex (A2/313 Haplotype) Derived from a Monosomy 6 Mutant Cell L

Sat, 1 Jan 1983 12:00:00 +0100 http://epub.ub.uni-muenchen.de/3127/ http://epub.ub.uni-muenchen.de/3127/1/3127.pdf Mellor, Andrew L.; Golden, L.; Weiß, Elisabeth; Bullman, H.; Flavell, Richard A. Mellor, Andrew L.; Golden, L.; Weiß, Elisabeth; Bullman, H. und Flavell, Richard A. (1983): Molecular cloning and analysis of H-2 class I genes of H-2b haplotype mice. In: Transplantation Proceedings, Vol. 15: pp. 2013-2015. Biolo