scholarly journals Identification of Multiple Gene Mutations Accounts for a new Genetic Architecture of Primary Ovarian Insufficiency

2016 ◽  
Vol 101 (12) ◽  
pp. 4541-4550 ◽  
Author(s):  
Justine Bouilly ◽  
Isabelle Beau ◽  
Sara Barraud ◽  
Valérie Bernard ◽  
Kemal Azibi ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Gene Mutations ◽  
Primary Ovarian Insufficiency ◽  
Potential Candidate ◽  
Missense Mutations ◽  
Ovarian Insufficiency ◽  
Monogenic Disorder ◽  
Gene Encoding ◽  
Multiple Loci

Context: Idiopathic primary ovarian insufficiency (POI) is a major cause of amenorrhea and infertility. POI affects 1% of women before age 40 years, and several genetic causes have been reported. To date, POI has been considered a monogenic disorder. Objective: The aim of this study was to identify novel gene variations and to investigate if individuals with POI harbor mutation in multiple loci. Patients and Methods: One hundred well-phenotyped POI patients were systematically screened for variants in 19 known POI loci (and potential candidate genes) using next-generation sequencing. Results: At least one rare protein-altering gene variant was identified in 19 patients, including missense mutations in new candidate genes, namely SMC1β and REC8 (involved in the cohesin complex) and LHX8, a gene encoding a transcription factor. Novel or recurrent deleterious mutations were also detected in the known POI candidate genes NOBOX, FOXL2, SOHLH1, FIGLA, GDF9, BMP15, and GALT. Seven patients harbor mutations in two loci, and this digenicity seems to influence the age of symptom onset. Conclusions: Genetic anomalies in women with POI are more frequent than previously believed. Digenic findings in several cases suggest that POI is not a purely monogenic disorder and points to a role of digenicity. The genotype-phenotype correlations in some kindreds suggest that a synergistic effect of several mutations may underlie the POI phenotype.

Fundamental role of BMP15 in human ovarian folliculogenesis revealed by null and missense mutations associated with primary ovarian insufficiency

2020 ◽  
Vol 41 (5) ◽  
pp. 983-997 ◽  
Author(s):  
Raffaella Rossetti ◽  
Ilaria Ferrari ◽  
Ilaria Bestetti ◽  
Silvia Moleri ◽  
Francesco Brancati ◽  
...  
Keyword(s):  
Primary Ovarian Insufficiency ◽  
Missense Mutations ◽  
Ovarian Insufficiency ◽  
Ovarian Folliculogenesis

scholarly journals Exploitation of a “hockey-puck” phenotype to identify pilus and biofilm regulators in Serratia marcescens through genetic analysis

2016 ◽  
Vol 62 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Robert M.Q. Shanks ◽  
Nicholas A. Stella ◽  
Kimberly M. Brothers ◽  
Denise M. Polaski
Keyword(s):  
Genetic Analysis ◽  
Serratia Marcescens ◽  
Candidate Genes ◽  
Biofilm Formation ◽  
Type I ◽  
Relative Importance ◽  
Gene Encoding ◽  
Uncharacterized Gene ◽  
Mutation Screen

Pili are essential adhesive determinants for many bacterial pathogens. A suppressor mutation screen that takes advantage of a pilus-mediated self-aggregative “hockey-puck” colony phenotype was designed to identify novel regulators of type I pili in Serratia marcescens. Mutations that decreased pilus biosynthesis mapped to the fimABCD operon; to the genes alaT, fkpA, and oxyR; upstream of the flagellar master regulator operon flhDC; and to an uncharacterized gene encoding a predicted DUF1401 domain. Biofilm formation and pilus-dependent agglutination assays were used to characterize the relative importance of the identified genes in pilus biosynthesis. Additional mutagenic or complementation analysis was used to verify the role of candidate genes in pilus biosynthesis. Presented data support a model that CRP negatively regulates pilus biosynthesis through increased expression of flhDC and decreased expression of oxyR. Further studies are warranted to determine the mechanism by which these genes mediate pilus biosynthesis or function.

scholarly journals Analysis of BMP15-Induced Transcriptome in Human Granulosa Cells for the Identification of Novel Candidate Genes for Primary Ovarian Insufficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A763-A764
Author(s):  
Raffaella Rossetti ◽  
Marco Fornili ◽  
Silvia Moleri ◽  
Ilaria Ferrari ◽  
Davide Gentilini ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
Granulosa Cells ◽  
Transcriptome Analysis ◽  
Primary Ovarian Insufficiency ◽  
Differentially Expressed ◽  
Incomplete Penetrance ◽  
Sequencing Analysis ◽  
Ovarian Insufficiency ◽  
Human Granulosa Cells

Abstract Primary Ovarian Insufficiency (POI) is a female fertility disorder which affects 1% of women before 40 years of age and manifests with amenorrhea, elevation of serum gonadotrophins and low estrogens. POI has a strong genetic component with incomplete penetrance. Several candidate genes have been described so far, however, its etiopathogenesis is mostly unknown. In order to discover the POI-related causative mechanisms, microarray transcriptome analysis in human granulosa cells (hGCs) stimulated with recombinant human BMP15 (rhBMP15) and next generation sequencing analysis (NGS) on the identified differentially expressed genes in a selected group of patients with POI were conducted on NGS Illumina platform. In the present study, we obtained 19 differentially expressed genes upon rhBMP15 stimulation in hGCs. Results: showed that all identified genes were upregulated and associated to pluripotency, inhibition of apoptosis, cell proliferation, BMP signaling and apoptosis. Moreover, we identified nine POI patients bearing six rare variants in 5 of the BMP15-induced genes (SAMD11, SMAD6, ID1, USP35, GPCR137C). The BMP15-induced transcriptome analysis in hGCs contributed the understanding of BMP15 role as transcriptional regulator, through the activation of transcriptional repressors, by inducing pathways inhibiting the ovarian follicle maturation, thus possibly maintaining an undifferentiated state of hGCs. These findings lead to the identification of novel candidate genes for POI.

scholarly journals Genetic analysis reveals candidate genes for activity QTL in the blind Mexican tetra,Astyanax mexicanus

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5189 ◽  
Author(s):  
Brian M. Carlson ◽  
Ian B. Klingler ◽  
Bradley J. Meyer ◽  
Joshua B. Gross
Keyword(s):  
Candidate Genes ◽  
Genetic Basis ◽  
Activity Patterns ◽  
Potential Candidate ◽  
Behavioral Phenotypes ◽  
Astyanax Mexicanus ◽  
Broad Array ◽  
Patterns Of Behavior ◽  
Surface Dwelling

Animal models provide useful tools for exploring the genetic basis of morphological, physiological and behavioral phenotypes. Cave-adapted species are particularly powerful models for a broad array of phenotypic changes with evolutionary, developmental and clinical relevance. Here, we explored the genetic underpinnings of previously characterized differences in locomotor activity patterns between the surface-dwelling and Pachón cave-dwelling populations ofAstyanax mexicanus.We identified multiple novel QTL underlying patterns in overall levels of activity (velocity), as well as spatial tank use (time spent near the top or bottom of the tank). Further, we demonstrated that different regions of the genome mediate distinct patterns in velocity and tank usage. We interrogated eight genomic intervals underlying these activity QTL distributed across six linkage groups. In addition, we employed transcriptomic data and draft genomic resources to generate and evaluate a list of 36 potential candidate genes. Interestingly, our data support the candidacy of a number of genes, but do not suggest that differences in the patterns of behavior observed here are the result of alterations to certain candidate genes described in other species (e.g., teleost multiple tissue opsins, melanopsins or members of the core circadian clockwork). This study expands our knowledge of the genetic architecture underlying activity differences in surface and cavefish. Future studies will help define the role of specific genes in shaping complex behavioral phenotypes inAstyanaxand other vertebrate taxa.

Author response for "An exome‐wide exploration of cases of primary ovarian insufficiency uncovers novel sequence variants and candidate genes"

2020 ◽  
Author(s):  
Maria Isabel Alvarez‐Mora ◽  
Anne‐Laure Todeschini ◽  
Sandrine Caburet ◽  
Lilach Peled Perets ◽  
Montserrat Mila ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Primary Ovarian Insufficiency ◽  
Author Response ◽  
Sequence Variants ◽  
Ovarian Insufficiency

scholarly journals Primary ovarian insufficiency in classic galactosemia: role of FSH dysfunction and timing of the lesion

2012 ◽  
Vol 36 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Cynthia S. Gubbels ◽  
Jolande A. Land ◽  
Johannes L. H. Evers ◽  
Jörgen Bierau ◽  
Paul P. C. A. Menheere ◽  
...  
Keyword(s):  
Primary Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Classic Galactosemia
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