CiteULike | Further Information

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Mendeley | Further Information

{"title"=>"Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene", "type"=>"journal", "authors"=>[{"first_name"=>"Nara L.M.", "last_name"=>"Sobreira", "scopus_author_id"=>"35146836600"}, {"first_name"=>"Elizabeth T.", "last_name"=>"Cirulli", "scopus_author_id"=>"15753450100"}, {"first_name"=>"Dimitrios", "last_name"=>"Avramopoulos", "scopus_author_id"=>"7004869949"}, {"first_name"=>"Elizabeth", "last_name"=>"Wohler", "scopus_author_id"=>"26429023200"}, {"first_name"=>"Gretchen L.", "last_name"=>"Oswald", "scopus_author_id"=>"13610016800"}, {"first_name"=>"Eric L.", "last_name"=>"Stevens", "scopus_author_id"=>"36349450500"}, {"first_name"=>"Dongliang", "last_name"=>"Ge", "scopus_author_id"=>"8963757100"}, {"first_name"=>"Kevin V.", "last_name"=>"Shianna", "scopus_author_id"=>"6508389190"}, {"first_name"=>"Jason P.", "last_name"=>"Smith", "scopus_author_id"=>"19640514100"}, {"first_name"=>"Jessica M.", "last_name"=>"Maia", "scopus_author_id"=>"7006248122"}, {"first_name"=>"Curtis E.", "last_name"=>"Gumbs", "scopus_author_id"=>"6602998114"}, {"first_name"=>"Jonathan", "last_name"=>"Pevsner", "scopus_author_id"=>"7005405147"}, {"first_name"=>"George", "last_name"=>"Thomas", "scopus_author_id"=>"7404576648"}, {"first_name"=>"David", "last_name"=>"Valle", "scopus_author_id"=>"7102075061"}, {"first_name"=>"Julie E.", "last_name"=>"Hoover-Fong", "scopus_author_id"=>"6603303275"}, {"first_name"=>"David B.", "last_name"=>"Goldstein", "scopus_author_id"=>"7402147672"}], "year"=>2010, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"359100526", "sgr"=>"77954158128", "issn"=>"15537390", "pmid"=>"20577567", "scopus"=>"2-s2.0-77954158128", "doi"=>"10.1371/journal.pgen.1000991", "isbn"=>"1553-7404"}, "id"=>"a38808bc-3816-3711-a03a-d54c5ca16189", "abstract"=>"Although more than 2,400 genes have been shown to contain variants that cause Mendelian disease, there are still several thousand such diseases yet to be molecularly defined. The ability of new whole-genome sequencing technologies to rapidly indentify most of the genetic variants in any given genome opens an exciting opportunity to identify these disease genes. Here we sequenced the whole genome of a single patient with the dominant Mendelian disease, metachondromatosis (OMIM 156250), and used partial linkage data from her small family to focus our search for the responsible variant. In the proband, we identified an 11 bp deletion in exon four of PTPN11, which alters frame, results in premature translation termination, and co-segregates with the phenotype. In a second metachondromatosis family, we confirmed our result by identifying a nonsense mutation in exon 4 of PTPN11 that also co-segregates with the phenotype. Sequencing PTPN11 exon 4 in 469 controls showed no such protein truncating variants, supporting the pathogenicity of these two mutations. This combination of a new technology and a classical genetic approach provides a powerful strategy to discover the genes responsible for unexplained Mendelian disorders.", "link"=>"http://www.mendeley.com/research/wholegenome-sequencing-single-proband-together-linkage-analysis-identifies-mendelian-disease-gene", "reader_count"=>194, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>12, "Researcher"=>58, "Student > Doctoral Student"=>8, "Student > Ph. D. Student"=>43, "Student > Postgraduate"=>7, "Student > Master"=>22, "Other"=>13, "Student > Bachelor"=>10, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>3, "Professor"=>13}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>12, "Researcher"=>58, "Student > Doctoral Student"=>8, "Student > Ph. D. Student"=>43, "Student > Postgraduate"=>7, "Student > Master"=>22, "Other"=>13, "Student > Bachelor"=>10, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>3, "Professor"=>13}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Agricultural and Biological Sciences"=>101, "Philosophy"=>1, "Computer Science"=>7, "Engineering"=>4, "Biochemistry, Genetics and Molecular Biology"=>23, "Mathematics"=>4, "Medicine and Dentistry"=>39, "Neuroscience"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>39}, "Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>1}, "Mathematics"=>{"Mathematics"=>4}, "Unspecified"=>{"Unspecified"=>5}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Engineering"=>{"Engineering"=>4}, "Neuroscience"=>{"Neuroscience"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>101}, "Computer Science"=>{"Computer Science"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>23}, "Philosophy"=>{"Philosophy"=>1}}, "reader_count_by_country"=>{"Austria"=>1, "Korea (South)"=>2, "Hong Kong"=>1, "Belgium"=>1, "United States"=>9, "Norway"=>1, "United Kingdom"=>3, "Mexico"=>1, "Italy"=>2, "France"=>1, "Germany"=>1}, "group_count"=>10}

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DataCite

Europe PMC Citations | Further Information

Europe PMC Database Citations | Further Information

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PubMed Central | Further Information

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/844565"], "description"=>"<p>Of families 1 (A) and 2 (B). The red arrow indicates the proband in each family. Segregation of the causal variant with the disease is shown in each family. Although III-1 and IV-1 in pedigree 1 were originally reported to be unaffected, we had the opportunity to examine them during the preparation of this manuscript and found that both had exostoses.</p>", "links"=>[], "tags"=>["genetics and genomics/genetics of disease"], "article_id"=>515008, "categories"=>["Genetics"], "users"=>["Nara L. M. Sobreira", "Elizabeth T. Cirulli", "Dimitrios Avramopoulos", "Elizabeth Wohler", "Gretchen L. Oswald", "Eric L. Stevens", "Dongliang Ge", "Kevin V. Shianna", "Jason P. Smith", "Jessica M. Maia", "Curtis E. Gumbs", "Jonathan Pevsner", "George Thomas", "David Valle", "Julie E. Hoover-Fong", "David B. Goldstein"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000991.g002", "stats"=>{"downloads"=>6, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pedigrees_/515008", "title"=>"Pedigrees.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-17 01:23:28"}
• {"files"=>["https://ndownloader.figshare.com/files/844679"], "description"=>"<p>The regions investigated for causal variants were 7p14.1, 8q24.1, 12q23, 2p25, 5q12.1, and 9q31.1–q33.1.</p>", "links"=>[], "tags"=>["linkage", "pedigree"], "article_id"=>515122, "categories"=>["Genetics"], "users"=>["Nara L. M. Sobreira", "Elizabeth T. Cirulli", "Dimitrios Avramopoulos", "Elizabeth Wohler", "Gretchen L. Oswald", "Eric L. Stevens", "Dongliang Ge", "Kevin V. Shianna", "Jason P. Smith", "Jessica M. Maia", "Curtis E. Gumbs", "Jonathan Pevsner", "George Thomas", "David Valle", "Julie E. Hoover-Fong", "David B. Goldstein"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000991.g003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plot_of_linkage_results_from_Pedigree_1_/515122", "title"=>"Plot of linkage results from Pedigree 1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-17 01:25:22"}
• {"files"=>["https://ndownloader.figshare.com/files/844395"], "description"=>"<p>(A) Dorsal view of the right hand of individual III-2 in Pedigree 2 at age 12 years, with residual exostoses following partial surgical removal over the metacarpophalangeal (MCP) joint of the second digit and primary exostoses of MCP of the fifth digit. (B) Dorsal view of the right hand of individual V-1 in Pedigree 1 at three years, showing deformity of the second digit secondary to exostoses of the middle phalanx and an exostoses over the middle phalanx of the fourth digit. (C) Radiograph of the dorsal view of the right hand of individual V-1 in Pedigree 1 at three years.</p>", "links"=>[], "tags"=>["genetics and genomics/genetics of disease"], "article_id"=>514835, "categories"=>["Genetics"], "users"=>["Nara L. M. Sobreira", "Elizabeth T. Cirulli", "Dimitrios Avramopoulos", "Elizabeth Wohler", "Gretchen L. Oswald", "Eric L. Stevens", "Dongliang Ge", "Kevin V. Shianna", "Jason P. Smith", "Jessica M. Maia", "Curtis E. Gumbs", "Jonathan Pevsner", "George Thomas", "David Valle", "Julie E. Hoover-Fong", "David B. Goldstein"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000991.g001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Manifestations_of_metachondromatosis_/514835", "title"=>"Manifestations of metachondromatosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-17 01:20:35"}
• {"files"=>["https://ndownloader.figshare.com/files/420486"], "description"=>"<div><p>Although more than 2,400 genes have been shown to contain variants that cause Mendelian disease, there are still several thousand such diseases yet to be molecularly defined. The ability of new whole-genome sequencing technologies to rapidly indentify most of the genetic variants in any given genome opens an exciting opportunity to identify these disease genes. Here we sequenced the whole genome of a single patient with the dominant Mendelian disease, metachondromatosis (OMIM 156250), and used partial linkage data from her small family to focus our search for the responsible variant. In the proband, we identified an 11 bp deletion in exon four of <em>PTPN11</em>, which alters frame, results in premature translation termination, and co-segregates with the phenotype. In a second metachondromatosis family, we confirmed our result by identifying a nonsense mutation in exon 4 of <em>PTPN11</em> that also co-segregates with the phenotype. Sequencing <em>PTPN11</em> exon 4 in 469 controls showed no such protein truncating variants, supporting the pathogenicity of these two mutations. This combination of a new technology and a classical genetic approach provides a powerful strategy to discover the genes responsible for unexplained Mendelian disorders.</p> </div>", "links"=>[], "tags"=>["whole-genome", "sequencing", "proband", "linkage", "identifies", "mendelian"], "article_id"=>143014, "categories"=>["Genetics"], "users"=>["Nara L. M. Sobreira", "Elizabeth T. Cirulli", "Dimitrios Avramopoulos", "Elizabeth Wohler", "Gretchen L. Oswald", "Eric L. Stevens", "Dongliang Ge", "Kevin V. Shianna", "Jason P. Smith", "Jessica M. Maia", "Curtis E. Gumbs", "Jonathan Pevsner", "George Thomas", "David Valle", "Julie E. Hoover-Fong", "David B. Goldstein"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000991", "stats"=>{"downloads"=>3, "page_views"=>42, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Whole_Genome_Sequencing_of_a_Single_Proband_Together_with_Linkage_Analysis_Identifies_a_Mendelian_Disease_Gene/143014", "title"=>"Whole-Genome Sequencing of a Single Proband Together with Linkage Analysis Identifies a Mendelian Disease Gene", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-06-17 00:50:14"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime | Further Information

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