Characterization of genomic imbalance in patients with balanced chromosomal rearrangements and abnormal phenotypes

Идентификация причин формирования аномалий развития у пациентов со сбалансированными хромосомными перестройками на сегодняшний день является актуальным и не в полной мере изученным направлением в цитогенетической практике, требующим разработки уникального подхода с использованием современных молекулярно-генетических технологий. Целью данного исследования явилась этиологическая диагностика геномного дисбаланса у пациентов со сбалансированными хромосомными перестройками и аномалиями развития. 20 пациентов с аномальным фенотипом и сбалансированными хромосомными перестройками, выявленными при стандартном кариотипировании, были обследованы методами хромосомного микроматричного анализа (ХМА) и FISH. Геномный дисбаланс (CNV) обнаружен в 13 случаях из 20, что составило 65%. Использование ХМА позволило установить, что в 69,2% случаев носительства сбалансированных хромосомных перестроек причиной аномального фенотипа являлось наличие микроделеций/микродупликаций, ассоциированных с точками разрывов при перестройках, а в 20,8% случаев наблюдались микроделеции/микродупликации на хромосомах, не задействованных в аберрациях. Несмотря на то, что ХМА позволил выявить причины аномалий развития в большинстве случаев, 7 пациентам (35%) не удалось установить окончательный молекулярно-цитогенетический диагноз. Более того, у некоторых пациентов выявленные CNVs не полностью отражают генотип-фенотип корреляцию, что требует проведения дополнительных молекулярно-генетических исследований. При отсутствии геномного дисбаланса при ХМА, а также при неполной генотип-фенотип корреляции, диагностика этиологии аномалий развития и патологического фенотипа должна быть продолжена молекулярными методами более высокого разрешения. Identification of genomic imbalances in cases with balanced chromosomal rearrangements and abnormal phenotype is a current trends in cytogenetics practice, requiring the development of unique approach using modern molecular genetic technologies. The aim of this study is diagnostics etiologies of the abnormal phenotype in patients with balanced chromosomal rearrangements. We report the investigations results of 20 patients with abnormal phenotype and balanced chromosomal rearrangements by conventional cytogenetic analysis. Genomic imbalances by microarray studies detected in 13 of 20 cases (65%). Most of CNVs was microdeletion or microduplication at a rearrangement breakpoint (69.2%) and 20.8% microdeletion/microduplication in other chromosomes.

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Current trends and challenges in analysis and characterization of engineered nanoparticles in seawater

Talanta ◽

10.1016/j.talanta.2021.122201 ◽

2021 ◽

Vol 226 ◽

pp. 122201

Author(s):

Andrei R. Timerbaev ◽

Olga V. Kuznetsova ◽

Bernhard K. Keppler

Keyword(s):

Engineered Nanoparticles ◽

Current Trends

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Metabolic Flux in Both the Purine Mononucleotide and Histidine Biosynthetic Pathways Can Influence Synthesis of the Hydroxymethyl Pyrimidine Moiety of Thiamine in Salmonella enterica

Journal of Bacteriology ◽

10.1128/jb.184.22.6130-6137.2002 ◽

2002 ◽

Vol 184 (22) ◽

pp. 6130-6137 ◽

Cited By ~ 26

Author(s):

Shara Allen ◽

Julie L. Zilles ◽

Diana M. Downs

Keyword(s):

Metabolic Flux ◽

Genetic Characterization ◽

Molecular Genetic ◽

Thiamine Pyrophosphate ◽

Wild Type ◽

Regulatory Pathway ◽

Informational Suppressors ◽

Pyrimidine Moiety ◽

Molecular Genetic Characterization

ABSTRACT Together, the biosyntheses of histidine, purines, and thiamine pyrophosphate (TPP) contain examples of convergent, divergent, and regulatory pathway integration. Mutations in two purine biosynthetic genes (purI and purH) affect TPP biosynthesis due to flux through the purine and histidine pathways. The molecular genetic characterization of purI mutants and their respective pseudorevertants resulted in the conclusion that <1% of the wild-type activity of the PurI enzyme was sufficient for thiamine but not for purine synthesis. The respective pseudorevertants were found to be informational suppressors. In addition, it was shown that accumulation of the purine intermediate aminoimidazole carboxamide ribotide inhibits thiamine synthesis, specifically affecting the conversion of aminoimidazole ribotide to hydroxymethyl pyrimidine.

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Autism Spectrum Disorder in a Girl with aDe NovoX;19 Balanced Translocation

Case Reports in Genetics ◽

10.1155/2012/578018 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Marcelo Razera Baruffi ◽

Deise Helena de Souza ◽

Rosana Aparecida Bicudo da Silva ◽

Ester Silveira Ramos ◽

Danilo Moretti-Ferreira

Keyword(s):

X Chromosome ◽

De Novo ◽

Recurrent Miscarriage ◽

Chromosomal Rearrangements ◽

Position Effect ◽

Autism Spectrum ◽

Balanced Translocation ◽

Replication Banding ◽

Conventional Cytogenetic Analysis ◽

Gonadal Dysfunction

Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with ade novoX;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed ade novobalanced translocation, with the karyotype 46,X,t(X;19)(p21.2;q13.4). Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY). Although abnormal phenotypes associated withde novobalanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process.

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Molecular genetic characterization of the regulatory region of the Xist gene in the common vole Microtus rossiaemeridionalis

Russian Journal of Genetics ◽

10.1134/s1022795409100056 ◽

2009 ◽

Vol 45 (10) ◽

pp. 1182-1191 ◽

Cited By ~ 2

Author(s):

K. E. Orishchenko ◽

E. A. Elisaphenko ◽

A. E. Kel ◽

S. M. Zakian

Keyword(s):

Genetic Characterization ◽

Molecular Genetic ◽

Regulatory Region ◽

Common Vole ◽

Xist Gene ◽

Microtus Rossiaemeridionalis ◽

The Common ◽

Molecular Genetic Characterization

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Gastrointestinal stromal tumor presenting as a rectovaginal mass. Clinicopathologic and molecular-genetic characterization of a rare tumor with a literature review

Human Pathology ◽

10.1016/j.humpath.2010.08.007 ◽

2011 ◽

Vol 42 (4) ◽

pp. 586-593 ◽

Cited By ~ 8

Author(s):

Antje-Friederike Pelz ◽

Abbas Agaimy ◽

Marc Daniels ◽

Matthias Evert ◽

Hans-Ulrich Schulz ◽

...

Keyword(s):

Literature Review ◽

Gastrointestinal Stromal Tumor ◽

Genetic Characterization ◽

Molecular Genetic ◽

Stromal Tumor ◽

Rare Tumor ◽

Molecular Genetic Characterization

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Molecular Characterization and Similarity Relationships among Flue-Cured Tobacco (Nicotiana tabacum L.) Genotypes Using Simple Sequence Repeat Markers

Notulae Botanicae Horti Agrobotanici Cluj-Napoca ◽

10.15835/nbha4027169 ◽

2012 ◽

Vol 40 (2) ◽

pp. 247

Author(s):

Soheila GHOLIZADEH ◽

Reza DARVISHZADEH ◽

Babak ABDOLLAHI MANDOULAKANI ◽

Iraj BERNOUSI ◽

Seyed Reza ALAVI ◽

...

Keyword(s):

Genetic Diversity ◽

Molecular Genetic ◽

Genetic Distances ◽

Similarity Coefficients ◽

Allele Number ◽

Nicotiana Tabacum L ◽

Ssr Loci ◽

Actual Degree ◽

Similarity Relationships

Characterization of genetic diversity has long been a major goal in tobacco breeding programs. Information on genetic diversity is essential for a rational use of genetic resources. In the present study, the genetic variation among 72 flue-cured tobacco genotypes was evaluated using microsatellite markers (SSRs). A set of 104 alleles was generated at 30 SSR loci. The mean number of alleles per locus (na) and the effective allele number (ne) were 3.467 and 2.358, respectively. The expected heterozygosity ranged from 0.29 to 0.75 with average of 0.54. Several methods were used to construct the similarity matrices and dendrograms. The co-phenetic correlation coefficient, which is a measure of the correlation between the similarities represented on the dendrograms and the actual degree of similarity, was calculated for each dendrogram. Among the different methods, the highest value (r=0.76368) was observed for the UPGMA created based on Jaccardâ€™s similarity coefficients. The genetic similarity among the tobacco genotypes calculated by using Jaccardâ€™s similarity coefficient ranged from 0.08 to 0.84, suggesting the presence of high molecular genetic variability among the studied tobacco genotypes. Based on UPGMA clustering method all studied flue-cured tobacco genotypes, except for â€˜Glustinusa Rashtâ€™, were placed in three distinct groups. We observed an obvious heterotic pattern in the studied flue-cured germplasm corresponding to genetic distances and classification dendrogram, which persuades exploitation of heterosis in flue-cured tobaccos.

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