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  1. Article ; Online: The Number of Candidate Variants in Exome Sequencing for Mendelian Disease under No Genetic Heterogeneity

    Jo Nishino / Shuhei Mano

    Computational and Mathematical Methods in Medicine, Vol

    2013  Volume 2013

    Abstract: There has been recent success in identifying disease-causing variants in Mendelian disorders by exome sequencing followed by simple filtering techniques. Studies generally assume complete or high penetrance. However, there are likely many failed and ... ...

    Abstract There has been recent success in identifying disease-causing variants in Mendelian disorders by exome sequencing followed by simple filtering techniques. Studies generally assume complete or high penetrance. However, there are likely many failed and unpublished studies due in part to incomplete penetrance or phenocopy. In this study, the expected number of candidate single-nucleotide variants (SNVs) in exome data for autosomal dominant or recessive Mendelian disorders was investigated under the assumption of “no genetic heterogeneity.” All variants were assumed to be under the “null model,” and sample allele frequencies were modeled using a standard population genetics theory. To investigate the properties of pedigree data, full-sibs were considered in addition to unrelated individuals. In both cases, particularly regarding full-sibs, the number of SNVs remained very high without controls. The high efficacy of controls was also confirmed. When controls were used with a relatively large total sample size (e.g., N=20, 50), filtering incorporating of incomplete penetrance and phenocopy efficiently reduced the number of candidate SNVs. This suggests that filtering is useful when an assumption of no “genetic heterogeneity” is appropriate and could provide general guidelines for sample size determination.
    Keywords Computer applications to medicine. Medical informatics ; R858-859.7
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Ancestral polymorphisms and sex-biased migration shaped the demographic history of brown bears and polar bears.

    Shigeki Nakagome / Shuhei Mano / Masami Hasegawa

    PLoS ONE, Vol 8, Iss 11, p e

    2013  Volume 78813

    Abstract: Recent studies have reported discordant gene trees in the evolution of brown bears and polar bears. Genealogical histories are different among independent nuclear loci and between biparentally inherited autosomal DNA (aDNA) and matrilineal mitochondrial ... ...

    Abstract Recent studies have reported discordant gene trees in the evolution of brown bears and polar bears. Genealogical histories are different among independent nuclear loci and between biparentally inherited autosomal DNA (aDNA) and matrilineal mitochondrial DNA (mtDNA). Based on multi-locus genomic sequences from aDNA and mtDNA, we inferred the population demography of brown and polar bears and found that brown bears have 6 times (aDNA) or more than 14 times (mtDNA) larger population sizes than polar bears and that polar bear lineage is derived from within brown bear diversity. In brown bears, the effective population size ratio of mtDNA to aDNA was at least 0.62, which deviated from the expected value of 0.25, suggesting matriarchal population due to female philopatry and male-biased migration. These results emphasize that ancestral polymorphisms and sex-biased migration may have contributed to conflicting branching patterns in brown and polar bears across aDNA genes and mtDNA.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612 ; 590
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Phylogeographic and Demographic Analysis of the Asian Black Bear (Ursus thibetanus) Based on Mitochondrial DNA.

    Jiaqi Wu / Naoki Kohno / Shuhei Mano / Yukio Fukumoto / Hideyuki Tanabe / Masami Hasegawa / Takahiro Yonezawa

    PLoS ONE, Vol 10, Iss 9, p e

    2015  Volume 0136398

    Abstract: The Asian black bear Ursus thibetanus is widely distributed in Asia and is adapted to broad-leaved deciduous forests, playing an important ecological role in the natural environment. Several subspecies of U. thibetanus have been recognized, one of which, ...

    Abstract The Asian black bear Ursus thibetanus is widely distributed in Asia and is adapted to broad-leaved deciduous forests, playing an important ecological role in the natural environment. Several subspecies of U. thibetanus have been recognized, one of which, the Japanese black bear, is distributed in the Japanese archipelago. Recent molecular phylogeographic studies clarified that this subspecies is genetically distantly related to continental subspecies, suggesting an earlier origin. However, the evolutionary relationship between the Japanese and continental subspecies remained unclear. To understand the evolution of the Asian black bear in relation to geological events such as climatic and transgression-regression cycles, a reliable time estimation is also essential. To address these issues, we determined and analyzed the mt-genome of the Japanese subspecies. This indicates that the Japanese subspecies initially diverged from other Asian black bears in around 1.46Ma. The Northern continental population (northeast China, Russia, Korean peninsula) subsequently evolved, relatively recently, from the Southern continental population (southern China and Southeast Asia). While the Japanese black bear has an early origin, the tMRCAs and the dynamics of population sizes suggest that it dispersed relatively recently in the main Japanese islands: during the late Middle and Late Pleistocene, probably during or soon after the extinction of the brown bear in Honshu in the same period. Our estimation that the population size of the Japanese subspecies increased rapidly during the Late Pleistocene is the first evidential signal of a niche exchange between brown bears and black bears in the Japanese main islands. This interpretation seems plausible but was not corroborated by paleontological evidence that fossil record of the Japanese subspecies limited after the Late Pleistocene. We also report here a new fossil record of the oldest Japanese black bear from the Middle Pleistocene, and it supports our new evolutionary hypothesis of the Japanese black bear.
    Keywords Medicine ; R ; Science ; Q
    Subject code 950
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Alopecia areata susceptibility variant in MHC region impacts expressions of genes contributing to hair keratinization and is involved in hair loss

    Akira Oka / Atsushi Takagi / Etsuko Komiyama / Nagisa Yoshihara / Shuhei Mano / Kazuyoshi Hosomichi / Shingo Suzuki / Yuko Haida / Nami Motosugi / Tomomi Hatanaka / Minoru Kimura / Mahoko Takahashi Ueda / So Nakagawa / Hiromi Miura / Masato Ohtsuka / Masayuki Tanaka / Tomoyoshi Komiyama / Asako Otomo / Shinji Hadano /
    Tomotaka Mabuchi / Stephan Beck / Hidetoshi Inoko / Shigaku Ikeda

    EBioMedicine, Vol 57, Iss , Pp 102810- (2020)

    2020  

    Abstract: ABSTRACT: Background: Alopecia areata (AA) is considered a highly heritable, T-cell-mediated autoimmune disease of the hair follicle. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a ... ...

    Abstract ABSTRACT: Background: Alopecia areata (AA) is considered a highly heritable, T-cell-mediated autoimmune disease of the hair follicle. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a genome region known to be associated with AA as compared to other regions. Methods: We engineered mice carrying AA risk allele identified by haplotype sequencing for the MHC region using allele-specific genome editing with the CRISPR/Cas9 system. Finally, we performed functional evaluations in the mice and AA patients with and without the risk allele. Findings: We identified a variant (rs142986308, p.Arg587Trp) in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene as the only non-synonymous variant in the AA risk haplotype. Furthermore, mice engineered to carry the risk allele displayed a hair loss phenotype. Transcriptomics further identified CCHCR1 as a novel component interacting with hair cortex keratin in hair shafts. Both, these alopecic mice and AA patients with the risk allele displayed morphologically impaired hair and comparable differential expression of hair-related genes, including hair keratin and keratin-associated proteins (KRTAPs). Interpretation: Our results implicate CCHCR1 with the risk allele in a previously unidentified subtype of AA based on aberrant keratinization in addition to autoimmune events. Funding: This work was supported by JSPS KAKENHI (JP16K10177) and the NIHR UCLH Biomedical Research center (BRC84/CN/SB/5984).
    Keywords Alopecia areata ; CRISPR/Cas9 ; MHC ; Haplotype ; Association ; Sequencing ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Speciation of two gobioid species, Pterogobius elapoides and Pterogobius zonoleucus revealed by multi-locus nuclear and mitochondrial DNA analyses

    Akihito / Fumihito Akishinonomiya / Masahiro Aizawa / Masami Hasegawa / Shuhei Mano / So Nakagawa / Takahiro Yonezawa / Takashi Gojobori / Tetsuji Nakabo / Yuji Ikeda / Yumi Umehara

    Gene. 2016 Feb. 01, v. 576, no. 2

    2016  

    Abstract: To understand how geographical differentiation of gobioid fish species led to speciation, two populations of the Pacific Ocean and the Sea of Japan for each of the two gobioid species, Pterogobius elapoides and Pterogobius zonoleucus, were studied in ... ...

    Abstract To understand how geographical differentiation of gobioid fish species led to speciation, two populations of the Pacific Ocean and the Sea of Japan for each of the two gobioid species, Pterogobius elapoides and Pterogobius zonoleucus, were studied in both morphological and molecular features. Analyzing mitochondrial genes, Akihito et al. (2008) suggested that P. zonoleucus does not form a monophyletic clade relative to P. elapoides, indicating that “Sea of Japan P. zonoleucus” and P. elapoides form a clade excluding “Pacific P. zonoleucus” as an outgroup. Because morphological classification clearly distinguish these two species and a gene tree may differ from a population tree, we examined three nuclear genes, S7RP, RAG1, and TBR1, in this work, in order to determine whether nuclear and mitochondrial trees are concordant, thus shedding light on the evolutionary history of this group of fishes. Importantly, nuclear trees were based on exactly the same individuals that were used for the previously published mtDNA trees. The tree based on RAG1 exon sequences suggested a closer relationship of P. elapoides with “Sea of Japan P. zonoleucus”, which was in agreement with the mitochondrial tree. In contrast, S7RP and TBR1 introns recovered a monophyletic P. zonoleucus. If the mitochondrial tree represents the population tree in which P. elapoides evolved from “Sea of Japan P. zonoleucus”, the population size of P. elapoides is expected to be smaller than that of “Sea of Japan P. zonoleucus”. This is because a smaller population of the new species is usually differentiated from a larger population of the ancestral species when the speciation occurred. However, we found no evidence of such a small population size during the evolution of P. elapoides. Therefore, we conclude that the monophyletic P. zonoleucus as suggested by S7RP and TBR1 most likely represents the population tree, which is consistent with the morphological classification. In this case, it is possible that the incongruent mitochondrial and RAG1 trees are either due to incomplete lineage sorting of ancestral polymorphisms or to introgression by hybridization. Because of a smaller effective population size of mitochondria compared with nuclear genes, the introgression might be a more likely scenario in explaining the incongruent mitochondrial tree than the incomplete lineage sorting. Because of smaller effective population size of “Sea of Japan P. zonoleucus” than that of P. elapoides, the direction of the introgression was likely to be from the latter to the former. This evolutionary work of the two gobioid species highlights the need of analyzing multiple gene trees for both nuclear and mitochondrial genes as well as scrutinization of morphological characteristics to obtain a population tree representing the organismal evolutionary history.
    Keywords exons ; fish ; genes ; introgression ; introns ; mitochondria ; mitochondrial DNA ; monophyly ; new species ; population size ; Pterogobius elapoides ; Pacific Ocean ; Sea of Japan
    Language English
    Dates of publication 2016-0201
    Size p. 593-602.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2015.10.014
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Domestication process of the goat revealed by an analysis of the nearly complete mitochondrial protein-encoding genes.

    Koh Nomura / Takahiro Yonezawa / Shuhei Mano / Shigehisa Kawakami / Andrew M Shedlock / Masami Hasegawa / Takashi Amano

    PLoS ONE, Vol 8, Iss 8, p e

    2013  Volume 67775

    Abstract: Goats (Capra hircus) are one of the oldest domesticated species, and they are kept all over the world as an essential resource for meat, milk, and fiber. Although recent archeological and molecular biological studies suggested that they originated in ... ...

    Abstract Goats (Capra hircus) are one of the oldest domesticated species, and they are kept all over the world as an essential resource for meat, milk, and fiber. Although recent archeological and molecular biological studies suggested that they originated in West Asia, their domestication processes such as the timing of population expansion and the dynamics of their selection pressures are little known. With the aim of addressing these issues, the nearly complete mitochondrial protein-encoding genes were determined from East, Southeast, and South Asian populations. Our coalescent time estimations suggest that the timing of their major population expansions was in the Late Pleistocene and significantly predates the beginning of their domestication in the Neolithic era (≈10,000 years ago). The ω (ratio of non-synonymous rate/synonymous substitution rate) for each lineage was also estimated. We found that the ω of the globally distributed haplogroup A which is inherited by more than 90% of goats examined, turned out to be extremely low, suggesting that they are under severe selection pressure probably due to their large population size. Conversely, the ω of the Asian-specific haplogroup B inherited by about 5% of goats was relatively high. Although recent molecular studies suggest that domestication of animals may tend to relax selective constraints, the opposite pattern observed in our goat mitochondrial genome data indicates the process of domestication is more complex than may be presently appreciated and cannot be explained only by a simple relaxation model.
    Keywords Medicine ; R ; Science ; Q
    Subject code 590 ; 612
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Detecting linkage between a trait and a marker in a random mating population without pedigree record.

    Shuhei Mano / Takaho A Endo / Akira Oka / Akira Ozawa / Takashi Gojobori / Hidetoshi Inoko

    PLoS ONE, Vol 4, Iss 3, p e

    2009  Volume 4956

    Abstract: Modern linkage-based approaches employing extended pedigrees are becoming powerful tools for localizing complex quantitative trait loci. For these linkage mapping methods, it is necessary to reconstruct extended pedigrees which include living individuals, ...

    Abstract Modern linkage-based approaches employing extended pedigrees are becoming powerful tools for localizing complex quantitative trait loci. For these linkage mapping methods, it is necessary to reconstruct extended pedigrees which include living individuals, using extensive pedigree records. Unfortunately, such records are not always easy to obtain and application of the linkage-based approaches has been restricted. Within a finite population under random mating, latent inbreeding rather than non-random inbreeding by consanguineous marriages is expected to occur and is attributable to coalescence in a finite population. Interestingly, it has been revealed that significant random inbreeding exists even in general human populations. Random inbreeding should be used to detect the hidden coancestry between individuals for a particular chromosomal position and it could also have application in linkage mapping methods. Here we present a novel method, named finite population based linkage mapping (FPL) method, to detect linkage between a quantitative trait and a marker via random inbreeding in a finite population without pedigree records. We show how to estimate coancestry for a chromosomal position between individuals by using multipoint Bayesian estimation. Subsequently, we describe the FPL method for detecting linkage via interval mapping method using a nonparametric test. We show that the FPL method does work via simulated data. For a random sample from a finite population, the FPL method is more powerful than a standard pedigree-based linkage mapping method with using genotypes of all parents of the sample. In addition, the FPL method was demonstrated by actual microsatellite genotype data of 750 Japanese individuals that are unrelated according to pedigree records to map a known Psoriasis susceptible locus. For samples without pedigree records, it was suggested that the FPL method require limited number of individuals, therefore would be better than other methods using thousands of individuals.
    Keywords Medicine ; R ; Science ; Q
    Subject code 310
    Language English
    Publishing date 2009-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Integrative annotation of 21,037 human genes validated by full-length cDNA clones.

    Tadashi Imanishi / Takeshi Itoh / Yutaka Suzuki / Claire O'Donovan / Satoshi Fukuchi / Kanako O Koyanagi / Roberto A Barrero / Takuro Tamura / Yumi Yamaguchi-Kabata / Motohiko Tanino / Kei Yura / Satoru Miyazaki / Kazuho Ikeo / Keiichi Homma / Arek Kasprzyk / Tetsuo Nishikawa / Mika Hirakawa / Jean Thierry-Mieg / Danielle Thierry-Mieg /
    Jennifer Ashurst / Libin Jia / Mitsuteru Nakao / Michael A Thomas / Nicola Mulder / Youla Karavidopoulou / Lihua Jin / Sangsoo Kim / Tomohiro Yasuda / Boris Lenhard / Eric Eveno / Yoshiyuki Suzuki / Chisato Yamasaki / Jun-ichi Takeda / Craig Gough / Phillip Hilton / Yasuyuki Fujii / Hiroaki Sakai / Susumu Tanaka / Clara Amid / Matthew Bellgard / Maria de Fatima Bonaldo / Hidemasa Bono / Susan K Bromberg / Anthony J Brookes / Elspeth Bruford / Piero Carninci / Claude Chelala / Christine Couillault / Sandro J de Souza / Marie-Anne Debily / Marie-Dominique Devignes / Inna Dubchak / Toshinori Endo / Anne Estreicher / Eduardo Eyras / Kaoru Fukami-Kobayashi / Gopal R Gopinath / Esther Graudens / Yoonsoo Hahn / Michael Han / Ze-Guang Han / Kousuke Hanada / Hideki Hanaoka / Erimi Harada / Katsuyuki Hashimoto / Ursula Hinz / Momoki Hirai / Teruyoshi Hishiki / Ian Hopkinson / Sandrine Imbeaud / Hidetoshi Inoko / Alexander Kanapin / Yayoi Kaneko / Takeya Kasukawa / Janet Kelso / Paul Kersey / Reiko Kikuno / Kouichi Kimura / Bernhard Korn / Vladimir Kuryshev / Izabela Makalowska / Takashi Makino / Shuhei Mano / Regine Mariage-Samson / Jun Mashima / Hideo Matsuda / Hans-Werner Mewes / Shinsei Minoshima / Keiichi Nagai / Hideki Nagasaki / Naoki Nagata / Rajni Nigam / Osamu Ogasawara / Osamu Ohara / Masafumi Ohtsubo / Norihiro Okada / Toshihisa Okido / Satoshi Oota / Motonori Ota / Toshio Ota / Tetsuji Otsuki / Dominique Piatier-Tonneau / Annemarie Poustka / Shuang-Xi Ren / Naruya Saitou / Katsunaga Sakai / Shigetaka Sakamoto / Ryuichi Sakate / Ingo Schupp / Florence Servant / Stephen Sherry / Rie Shiba / Nobuyoshi Shimizu / Mary Shimoyama / Andrew J Simpson / Bento Soares / Charles Steward / Makiko Suwa / Mami Suzuki / Aiko Takahashi / Gen Tamiya / Hiroshi Tanaka / Todd Taylor / Joseph D Terwilliger / Per Unneberg / Vamsi Veeramachaneni / Shinya Watanabe / Laurens Wilming / Norikazu Yasuda / Hyang-Sook Yoo / Marvin Stodolsky / Wojciech Makalowski / Mitiko Go / Kenta Nakai / Toshihisa Takagi / Minoru Kanehisa / Yoshiyuki Sakaki / John Quackenbush / Yasushi Okazaki / Yoshihide Hayashizaki / Winston Hide / Ranajit Chakraborty / Ken Nishikawa / Hideaki Sugawara / Yoshio Tateno / Zhu Chen / Michio Oishi / Peter Tonellato / Rolf Apweiler / Kousaku Okubo / Lukas Wagner / Stefan Wiemann / Robert L Strausberg / Takao Isogai / Charles Auffray / Nobuo Nomura / Takashi Gojobori / Sumio Sugano

    PLoS Biology, Vol 2, Iss 6, p e

    2004  Volume 162

    Abstract: The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation ... ...

    Abstract The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
    Keywords Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2004-06-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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