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Your search keyword '"Farheen Daudvohra"' showing total 3 results
Start Over Author "Farheen Daudvohra" Topic cell biology
3 results on '"Farheen Daudvohra"'

1. PCD Detect: enhancing ciliary features through image averaging and classification

Author

Thomas Burgoyne, Farheen Daudvohra, Andreia Pinto, Hannah M. Mitchison, Amelia Shoemark, Mitali P. Patel, and Claire Hogg

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Axoneme, Genotype, Physiology, Biology, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), medicine, Humans, Cilia, Lung function, Primary ciliary dyskinesia, Lung, Kartagener Syndrome, Cilium, Dyneins, Cell Biology, medicine.disease, Phenotype, 030104 developmental biology, medicine.anatomical_structure, 030228 respiratory system, Mutation, Motile cilium, Image averaging, Ciliary Motility Disorders
Abstract

Primary ciliary dyskinesia (PCD) is an inherited disorder of the motile cilia. Early accurate diagnosis is important to help prevent lung damage in childhood and to preserve lung function. Confirmation of a diagnosis traditionally relied on assessment of ciliary ultrastructure by transmission electron microscopy (TEM); however, >50 known PCD genes have made the identification of biallelic mutations a viable alternative to confirm diagnosis. TEM and genotyping lack sensitivity, and research to improve accuracy of both is required. TEM can be challenging when a subtle or partial ciliary defect is present or affected cilia structures are difficult to identify due to poor contrast. Here, we demonstrate software to enhance TEM ciliary images and reduce background by averaging ciliary features. This includes an option to classify features into groups based on their appearance, to generate multiple averages when a nonhomogeneous abnormality is present. We validated this software on images taken from subjects with well-characterized PCD caused by variants in the outer dynein arm (ODA) heavy chain gene DNAH5. Examining more difficult to diagnose cases, we detected 1) regionally restricted absence of the ODAs away from the ciliary base, in a subject carrying mutations in DNAH9; 2) loss of the typically poorly contrasted inner dynein arms; and 3) sporadic absence of part of the central pair complex in subjects carrying mutations in HYDIN, including one case with an unverified genetic diagnosis. We show that this easy-to-use software can assist in detailing relationships between genotype and ultrastructural phenotype, improving diagnosis of PCD.

Published
2020

3. Mutations in Outer Dynein Arm Heavy Chain DNAH9 Cause Motile Cilia Defects and Situs Inversus

Author

Siobhán B. Carr, Anne Aubusson-Fleury, Mellisa Dixon, Amelia Shoemark, Thomas Burgoyne, Jean-François Papon, Lucy Jenkins, Lucie Thomas, Claire Hogg, Robert A. Hirst, Estelle Escudier, Farheen Daudvohra, Hannah M. Mitchison, Bruno Louis, Andrew G. Nicholson, Mitali P. Patel, Pierrick le Borgne, Serge Amselem, Paul Aurora, Thomas Cullup, Michel Lemullois, Anne-Marie Tassin, Marie Legendre, Joseph Hayes, Mahmoud R. Fassad, Christopher O'Callaghan, Great Ormond Street Institute of Child Health (UCL), University College of London [London] (UCL), Alexandria University [Alexandrie], Royal Brompton and Harefield NHS Foundation Trust, University of Dundee, Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Leicester, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Biogenèse et Fonction de la Structure Centriolaire et Ciliaire (BIOCIL), Département Biologie Cellulaire (BioCell), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Service d’ORL et de chirurgie cervico-faciale [CHU Le Kremlin-Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Fondation pour la Recherche Médicale (DEQ20120323689) Legs Poix from the Chancellerie des Universités Investissements d’Avenir (RaDiCo program, ANR-10-COHO-0003). Action Medical Research (GN2101, H.M.M.)Great Ormond Street Children’s Charity grant (V4515, H.M.M.)Leadership awards (V1299, V2217, H.M.M.).British Council Newton-Mosharafa Fund and the Ministry of Higher Education, Egypt.National Institute of Health Research and Health Education England. The authors participate in the COST Action BEAT-PCD: Better Evidence to Advance Therapeutic options for PCD network (BM1407) BM1407 COST Action STSM Grants, ANR-10-COHO-0003,RADICO,Cohorte nationale maladies rares(2010), Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique et embryologie médicales [CHU Trousseau], Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), and UF de Génétique moléculaire [CHU Trousseau]

Subjects
0301 basic medicine, Male, Adolescent, Mucociliary clearance, diagnosis, [SDV]Life Sciences [q-bio], Dynein, Respiratory System, primary ciliary dyskinesia, Biology, tomography, situs inversus, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Motor protein, 03 medical and health sciences, 0302 clinical medicine, Report, medicine, Humans, genetics, Amino Acid Sequence, Cilia, motile cilia, Child, genes, Genetics (clinical), Primary ciliary dyskinesia, dynein, Cilium, Dyneins, High-Throughput Nucleotide Sequencing, Axonemal Dyneins, medicine.disease, 3. Good health, Cell biology, DNAH9, Situs inversus, dyskinesia, 030104 developmental biology, 030228 respiratory system, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Child, Preschool, Motile cilium, Outer dynein arm, mutation, Sequence Alignment, Ciliary Motility Disorders
Abstract

International audience; Motile cilia move body fluids and gametes and the beating of cilia lining the airway epithelial surfaces ensures that they are kept clear and protected from inhaled pathogens and consequent respiratory infections. Dynein motor proteins provide mechanical force for cilia beating. Dynein mutations are a common cause of primary ciliary dyskinesia (PCD), an inherited condition characterized by deficient mucociliary clearance and chronic respiratory disease coupled with laterality disturbances and subfertility. Using next-generation sequencing, we detected mutations in the ciliary outer dynein arm (ODA) heavy chain gene DNAH9 in individuals from PCD clinics with situs inversus and in one case male infertility. DNAH9 and its partner heavy chain DNAH5 localize to type 2 ODAs of the distal cilium and in DNAH9-mutated nasal respiratory epithelial cilia we found a loss of DNAH9/DNAH5-containing type 2 ODAs that was restricted to the distal cilia region. This confers a reduced beating frequency with a subtle beating pattern defect affecting the motility of the distal cilia portion. 3D electron tomography ultrastructural studies confirmed regional loss of ODAs from the distal cilium, manifesting as either loss of whole ODA or partial loss of ODA volume. Paramecium DNAH9 knockdown confirms an evolutionarily conserved function for DNAH9 in cilia motility and ODA stability. We find that DNAH9 is widely expressed in the airways, despite DNAH9 mutations appearing to confer symptoms restricted to the upper respiratory tract. In summary, DNAH9 mutations reduce cilia function but some respiratory mucociliary clearance potential may be retained, widening the PCD disease spectrum.

Published
2018

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