Startling Mosaicism of the Y-Chromosome and Tandem Duplication of the SRY and DAZ Genes in Patients with Turner Syndrome
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{"title"=>"Startling mosaicism of the Y-chromosome and tandem duplication of the SRY and DAZ genes in patients with turner syndrome", "type"=>"journal", "authors"=>[{"first_name"=>"Sanjay", "last_name"=>"Premi", "scopus_author_id"=>"11339983300"}, {"first_name"=>"Jyoti", "last_name"=>"Srivastava", "scopus_author_id"=>"11339045200"}, {"first_name"=>"Ganesan", "last_name"=>"Panneer", "scopus_author_id"=>"25723675700"}, {"first_name"=>"Sher", "last_name"=>"Ali", "scopus_author_id"=>"7403094068"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"352761157", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"57049113884", "pmid"=>"19030103", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0003796", "scopus"=>"2-s2.0-57049113884"}, "id"=>"c138c30a-2b67-3af2-a62e-af804193eede", "abstract"=>"Presence of the human Y-chromosome in females with Turner Syndrome (TS) enhances the risk of development of gonadoblastoma besides causing several other phenotypic abnormalities. In the present study, we have analyzed the Y chromosome in 15 clinically diagnosed Turner Syndrome (TS) patients and detected high level of mosaicisms ranging from 45,XO:46,XY = 100:0% in 4; 45,XO:46,XY:46XX = 4:94:2 in 8; and 45,XO:46,XY:46XX = 50:30:20 cells in 3 TS patients, unlike previous reports showing 5-8% cells with Y- material. Also, no ring, marker or di-centric Y was observed in any of the cases. Of the two TS patients having intact Y chromosome in >85% cells, one was exceptionally tall. Both the patients were positive for SRY, DAZ, CDY1, DBY, UTY and AZFa, b and c specific STSs. Real Time PCR and FISH demonstrated tandem duplication/multiplication of the SRY and DAZ genes. At sequence level, the SRY was normal in 8 TS patients while the remaining 7 showed either absence of this gene or known and novel mutations within and outside of the HMG box. SNV/SFV analysis showed normal four copies of the DAZ genes in these 8 patients. All the TS patients showed aplastic uterus with no ovaries and no symptom of gonadoblastoma. Present study demonstrates new types of polymorphisms indicating that no two TS patients have identical genotype-phenotype. Thus, a comprehensive analysis of more number of samples is warranted to uncover consensus on the loci affected, to be able to use them as potential diagnostic markers.", "link"=>"http://www.mendeley.com/research/startling-mosaicism-ychromosome-tandem-duplication-sry-daz-genes-patients-turner-syndrome", "reader_count"=>19, "reader_count_by_academic_status"=>{"Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>14, "Arts and Humanities"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Italy"=>1}, "group_count"=>0}

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  • {"files"=>["https://ndownloader.figshare.com/files/915433"], "description"=>"<p>STSs used are given on the right and sample IDs on top. The IDs ‘AT’ are Turners and their details are given in the <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003796#pone-0003796-t001\" target=\"_blank\">table 1</a>. A10 and A10g represent blood and semen DNA samples, respectively, from a single azoospermic male. HF denotes human female DNA sample. β-actin primers were used to normalize the quality and quantity of DNA used as template in PCR. Note presence of most of the STSs in Turners AT1 and AT15. Some STSs were positive in case of Turner AT13 as well but owing to non-availability of the fresh blood, the FISH experiments could not be conducted (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003796#pone-0003796-t001\" target=\"_blank\">Tables 1</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003796#pone-0003796-t002\" target=\"_blank\">2</a> for details of the Turner patients).</p>", "links"=>[], "tags"=>["gels", "sts", "chromosomes", "ts"], "article_id"=>585890, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003796.g003", "stats"=>{"downloads"=>4, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_gels_showing_STS_mapping_of_the_Y_chromosomes_in_TS_patients_/585890", "title"=>"Representative gels showing STS mapping of the Y chromosomes in TS patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-11-24 01:38:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/916526"], "description"=>"<p>Numbers in parenthesis under karyotype denote percentage of the cells with the particular chromosomal constitution. Numbers in parenthesis under karyotype denote percentage of the cells with the particular chromosomal constitution. All the karyotypes were confirmed analyzing ∼400 metaphase chromosome sets per individual. <sup>#</sup> Undt” is for undetermined owing to high level of mosaicism.</p>", "links"=>[], "tags"=>["polymorphism", "genes", "turner"], "article_id"=>586980, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003796.t002", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Copy_number_polymorphism_of_the_SRY_and_DAZ_genes_in_the_Turner_Syndrome_patients_/586980", "title"=>"Copy number polymorphism of the <i>SRY</i> and <i>DAZ</i> genes in the Turner Syndrome patients.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-11-24 01:56:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/915582"], "description"=>"<p>(A) <i>AZFa</i> region of the human Y chromosome indicated as horizontal bar with centromere towards left and Yq to right. Various STS markers used for the analysis of the <i>AZF</i>a region and the candidate genes (<i>DBY</i>, <i>UTY</i>, <i>USP9Y</i>) are mentioned in the figure. The positions of provirus element A and B are shown by red dotted lines. (B) Detailed structure of the provirus A and B. Note the LINE insertion in provirus B. Various STS markers used to assess recombination events involving provirus elements are also indicated. (C) Results of the provirus (HERV) mapping of the Turner's syndrome. It may be noted that none of the males showed characteristic patterns of HERV mediated recombination leading to the AZFa deletion or duplication.</p>", "links"=>[], "tags"=>["chromosome", "turner", "patients", "herv", "mediated"], "article_id"=>586034, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003796.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_the_AZFa_region_of_the_Y_chromosome_in_Turner_Patients_for_possible_HERV_mediated_recombination_/586034", "title"=>"Analysis of the <i>AZFa</i> region of the Y chromosome in Turner Patients for possible HERV mediated recombination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-11-24 01:40:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/915932"], "description"=>"<p>(A) and (B) Similar to the <i>SRY</i>, lack of Y chromosome in some Turners resulted a increase in Ct values of <i>DAZ</i> genes. (C) Representative plot showing 8 copies instead of 4 of the <i>DAZ</i> gene in Turners Patients. (D) Representative plot showing normal 4 copies of the <i>DAZ</i> genes with ΔCt = −1.</p>", "links"=>[], "tags"=>["pcr", "plots", "genes", "turner"], "article_id"=>586382, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003796.g006", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Real_Time_PCR_plots_for_copy_number_calculation_of_the_DAZ_genes_in_Turner_patients_/586382", "title"=>"Real Time PCR plots for copy number calculation of the <i>DAZ</i> genes in Turner patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-11-24 01:46:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/915256"], "description"=>"<p>(which binds simultaneously to the <i>SRY</i> gene and centromere of the X chromosome) within the interphase nuclei and metaphase chromosomes of Turner AT1. (A i–iv) shows presence of both X (green dot) and Y (red dot) chromosomes in the interphase nuclei. Note structurally normal Y chromosome and absence of ring or dicentric one in (Bi) and (Ci) where the <i>SRY</i> gene is localized on the Yp. Some cells showed absence of the X chromosome, denoted by pink arrows (Bii) and (Cii). The classical Turner karyotypes (45, XO) are shown by yellow arrows. Some cells showed 47, XYY (Civ). (D), Cells without Y but variable numbers of X chromosome ranging from 1 (45, XO) to 2 (46, XX) were also detected. Only representative cells with different karyotypes are shown here. Single localized signal of the <i>SRY</i> gene (copy number 16) in AT1 suggests tandem duplication of this gene.</p>", "links"=>[], "tags"=>["hybridization", "lsi", "probe"], "article_id"=>585713, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003796.g001", "stats"=>{"downloads"=>2, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fluorescence_in_situ_hybridization_FISH_using_LSI_SRY_probe_from_VYSIS_/585713", "title"=>"Fluorescence <i>in-situ</i> hybridization (FISH) using LSI <i>SRY</i> probe from VYSIS", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-11-24 01:35:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/916346"], "description"=>"<p>In total ∼ 40 <i>SRY</i> recombinant plasmids were sequenced identifying two types of sequences AT1F2 and ATF3. Note that except the change N41I in AT1F2, rest of the amino acid sequence was normal. This highlights <i>de novo</i> status of the amino acid changes detected in the Turner AT1.</p>", "links"=>[], "tags"=>["changes", "corresponding", "nucleotide", "turner"], "article_id"=>586802, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003796.g009", "stats"=>{"downloads"=>5, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Amino_acid_changes_corresponding_to_nucleotide_sequence_of_the_SRY_gene_in_father_of_a_Turner_patient_AT1_/586802", "title"=>"Amino acid changes corresponding to nucleotide sequence of the <i>SRY</i> gene in father of a Turner patient AT1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-11-24 01:53:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/915359"], "description"=>"<p>Note absence of the <i>SRY</i> signals in all the cells. No detectable Y chromosome at the level of PCR or G-banding was detected in this patient. The alterations detected in the number of X-Chromosomes are indicated by arrows. Pink arrows show cells with three X-Chromosomes (47, XXX) and the yellow ones highlights the cells with a single X-Chromosome (45, XO). Remaining interphases showed two X-Chromosomes (46, XX). Analysis of metaphase chromosomes (i–ii) further substantiated absence of the Y-chromosome. This is in contrast to Turner AT1 where >80% cells harbored Y-chromosome.</p>", "links"=>[], "tags"=>["interphase", "nuclei", "metaphase", "chromosomes", "turner"], "article_id"=>585811, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003796.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FISH_with_interphase_nuclei_and_metaphase_chromosomes_of_a_Turner_patient_AT4_with_LSI_SRY_probe_/585811", "title"=>"FISH with interphase nuclei and metaphase chromosomes of a Turner patient (AT4) with LSI-<i>SRY</i> probe.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-11-24 01:36:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/916060"], "description"=>"<p>The <i>A</i>, <i>B</i>, <i>C</i> and <i>D</i> denote <i>DAZ</i> probes (supplementary <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003796#pone-0003796-g001\" target=\"_blank\">figure 1</a>) and, <i>tr</i> and <i>fl</i> are for texas red and fluorescein labels, respectively. (A) Note presence of 2 expected signals or a single one owing to overlap in several cells. Some cells lacked signals (v) and others showed 3 signals in place of 2 (vi). (B) Dual probe FISH with <i>DAZ</i> probe <i>A</i> in red and <i>B</i> in green. Expected overlap of the probes <i>A</i> and <i>B</i> was not observed in most of the cells except a few (iii). Localized <i>DAZ</i> signals detected by FISH and multiple copies by Real Time PCR highlight the events of tandem duplication. (C) Analysis of the <i>AZF</i>c green amplicons in Turners. Note the presence of all three green amplicons observed in the form of 3 well separated signals. Few cells even showed 2 signals where 1 was of higher intensity compared to that detected in others (vi, vii). This suggests a possible sequence re-modulation or reorganization of the <i>AZF</i>c in some percentage of cells in TS patients. The conclusions were based following analyses of 400 metaphase/interphase cells from each Turner Patient.</p>", "links"=>[], "tags"=>["genes", "turner"], "article_id"=>586516, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003796.g007", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FISH_for_DAZ_genes_in_Turner_Patient_AT1_/586516", "title"=>"FISH for <i>DAZ</i> genes in Turner Patient AT1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-11-24 01:48:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/915713"], "description"=>"<p>(A) Due to very low number or absence of cells harboring Y chromosome in Turners' AT2 to AT12, the Ct for <i>SRY</i> remained undetermined and thus copy number of the same could not be calculated. (B) Real Time PCR plot of a normal male with ΔCt = 1 corresponding to copies of the <i>SRY</i> = 1. (C) and (D) represent plots for additional mosaicisms in the context of percentage of the Y chromosome (and thus for the <i>SRY</i> gene) in Turner AT13. The ΔCt values (2 or 4) are unexpected, suggesting that percentage of cells harboring <i>SRY</i> is less compared to the ones harboring <i>RNase</i>P gene. In Turners AT1 and AT15, ΔCt −3 and −2 respectively, were observed resulting in 16 and 8 copies of the <i>SRY</i> gene (not shown).</p>", "links"=>[], "tags"=>["pcr", "plots", "turner"], "article_id"=>586168, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003796.g005", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Real_Time_PCR_plots_for_SRY_in_Turner_patients_/586168", "title"=>"Real Time PCR plots for <i>SRY</i> in Turner patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-11-24 01:42:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/916195"], "description"=>"<p>Note the amino acid changes within, upstream and downstream regions of the HMG box which is underlined. Most of these changes detected in the present study were not described earlier.</p>", "links"=>[], "tags"=>["changes", "corresponding", "nucleotide", "turners", "at1"], "article_id"=>586643, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003796.g008", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Amino_acid_changes_corresponding_to_nucleotide_sequence_of_the_SRY_gene_in_Turners_AT1_and_AT15_/586643", "title"=>"Amino acid changes corresponding to nucleotide sequence of the <i>SRY</i> gene in Turners AT1 and AT15.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-11-24 01:50:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/452611", "https://ndownloader.figshare.com/files/452652"], "description"=>"<div><p>Presence of the human Y-chromosome in females with Turner Syndrome (TS) enhances the risk of development of gonadoblastoma besides causing several other phenotypic abnormalities. In the present study, we have analyzed the Y chromosome in 15 clinically diagnosed Turner Syndrome (TS) patients and detected high level of mosaicisms ranging from 45,XO:46,XY = 100:0% in 4; 45,XO:46,XY:46XX = 4:94:2 in 8; and 45,XO:46,XY:46XX = 50:30:20 cells in 3 TS patients, unlike previous reports showing 5–8% cells with Y- material. Also, no ring, marker or di-centric Y was observed in any of the cases. Of the two TS patients having intact Y chromosome in >85% cells, one was exceptionally tall. Both the patients were positive for <em>SRY</em>, <em>DAZ</em>, <em>CDY1</em>, <em>DBY</em>, <em>UTY</em> and <em>AZFa</em>, <em>b</em> and <em>c</em> specific STSs. Real Time PCR and FISH demonstrated tandem duplication/multiplication of the <em>SRY</em> and <em>DAZ</em> genes. At sequence level, the <em>SRY</em> was normal in 8 TS patients while the remaining 7 showed either absence of this gene or known and novel mutations within and outside of the HMG box. SNV/SFV analysis showed normal four copies of the <em>DAZ</em> genes in these 8 patients. All the TS patients showed aplastic uterus with no ovaries and no symptom of gonadoblastoma. Present study demonstrates new types of polymorphisms indicating that no two TS patients have identical genotype-phenotype. Thus, a comprehensive analysis of more number of samples is warranted to uncover consensus on the loci affected, to be able to use them as potential diagnostic markers.</p></div>", "links"=>[], "tags"=>["startling", "mosaicism", "y-chromosome", "tandem", "duplication", "genes", "patients", "turner"], "article_id"=>149149, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0003796.s001", "https://dx.doi.org/10.1371/journal.pone.0003796.s002"], "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Startling_Mosaicism_of_the_Y_Chromosome_and_Tandem_Duplication_of_the_SRY_and_DAZ_Genes_in_Patients_with_Turner_Syndrome/149149", "title"=>"Startling Mosaicism of the Y-Chromosome and Tandem Duplication of the <em>SRY</em> and <em>DAZ</em> Genes in Patients with Turner Syndrome", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2008-11-24 02:32:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/916487"], "description"=>"<p># NM = Normal male, NF = Normal female, NA = Not available, USG = Ultrasonography, PRL = Prolactin releasing hormone, TSH = Thyroid stimulating hormone, FSH = Follicle stimulating hormone, LH = Luteinizing hormone. Numbers in parenthesis under karyotype denote percentage of the cells with the particular chromosomal constitution. All the karyotypes were confirmed analyzing ∼400 metaphase chromosome sets per individual.</p>", "links"=>[], "tags"=>["karyotypes", "hormonal", "profiles", "turner", "patients"], "article_id"=>586943, "categories"=>["Genetics"], "users"=>["Sanjay Premi", "Jyoti Srivastava", "Ganesan Panneer", "Sher Ali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003796.t001", "stats"=>{"downloads"=>7, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Details_of_the_karyotypes_and_hormonal_profiles_of_different_Turner_patients_analyzed_/586943", "title"=>"Details of the karyotypes and hormonal profiles of different Turner patients analyzed<sup>#</sup>", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-11-24 01:55:43"}

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Relative Metric

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