17P13.3 Microdeletions
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Searching the Genomes of Inbred Mouse Strains for Incompatibilities That Reproductively Isolate Their Wild Relatives
Journal of Heredity 2007:98(2):115–122 ª The American Genetic Association. 2007. All rights reserved. doi:10.1093/jhered/esl064 For permissions, please email: [email protected]. Advance Access publication January 5, 2007 Searching the Genomes of Inbred Mouse Strains for Incompatibilities That Reproductively Isolate Their Wild Relatives BRET A. PAYSEUR AND MICHAEL PLACE From the Laboratory of Genetics, University of Wisconsin, Madison, WI 53706. Address correspondence to the author at the address above, or e-mail: [email protected]. Abstract Identification of the genes that underlie reproductive isolation provides important insights into the process of speciation. According to the Dobzhansky–Muller model, these genes suffer disrupted interactions in hybrids due to independent di- vergence in separate populations. In hybrid populations, natural selection acts to remove the deleterious heterospecific com- binations that cause these functional disruptions. When selection is strong, this process can maintain multilocus associations, primarily between conspecific alleles, providing a signature that can be used to locate incompatibilities. We applied this logic to populations of house mice that were formed by hybridization involving two species that show partial reproductive isolation, Mus domesticus and Mus musculus. Using molecular markers likely to be informative about species ancestry, we scanned the genomes of 1) classical inbred strains and 2) recombinant inbred lines for pairs of loci that showed extreme linkage disequi- libria. By using the same set of markers, we identified a list of locus pairs that displayed similar patterns in both scans. These genomic regions may contain genes that contribute to reproductive isolation between M. domesticus and M. -
PROTEOMIC ANALYSIS of HUMAN URINARY EXOSOMES. Patricia
ABSTRACT Title of Document: PROTEOMIC ANALYSIS OF HUMAN URINARY EXOSOMES. Patricia Amalia Gonzales Mancilla, Ph.D., 2009 Directed By: Associate Professor Nam Sun Wang, Department of Chemical and Biomolecular Engineering Exosomes originate as the internal vesicles of multivesicular bodies (MVBs) in cells. These small vesicles (40-100 nm) have been shown to be secreted by most cell types throughout the body. In the kidney, urinary exosomes are released to the urine by fusion of the outer membrane of the MVBs with the apical plasma membrane of renal tubular epithelia. Exosomes contain apical membrane and cytosolic proteins and can be isolated using differential centrifugation. The analysis of urinary exosomes provides a non- invasive means of acquiring information about the physiological or pathophysiological state of renal cells. The overall objective of this research was to develop methods and knowledge infrastructure for urinary proteomics. We proposed to conduct a proteomic analysis of human urinary exosomes. The first objective was to profile the proteome of human urinary exosomes using liquid chromatography-tandem spectrometry (LC- MS/MS) and specialized software for identification of peptide sequences from fragmentation spectra. We unambiguously identified 1132 proteins. In addition, the phosphoproteome of human urinary exosomes was profiled using the neutral loss scanning acquisition mode of LC-MS/MS. The phosphoproteomic profiling identified 19 phosphorylation sites corresponding to 14 phosphoproteins. The second objective was to analyze urinary exosomes samples isolated from patients with genetic mutations. Polyclonal antibodies were generated to recognize epitopes on the gene products of these genetic mutations, NKCC2 and MRP4. The potential usefulness of urinary exosome analysis was demonstrated using the well-defined renal tubulopathy, Bartter syndrome type I and using the single nucleotide polymorphism in the ABCC4 gene. -
Containing Interneurons in Hippocampus of a Murine
RESEARCH ARTICLE Emergence of non-canonical parvalbumin- containing interneurons in hippocampus of a murine model of type I lissencephaly Tyler G Ekins1,2, Vivek Mahadevan1, Yajun Zhang1, James A D’Amour1,3, Gu¨ lcan Akgu¨ l1, Timothy J Petros1, Chris J McBain1* 1Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States; 2NIH-Brown University Graduate Partnership Program, Providence, United States; 3Postdoctoral Research Associate Training Program, National Institute of General Medical Sciences, Bethesda, United States Abstract Type I lissencephaly is a neuronal migration disorder caused by haploinsuffiency of the PAFAH1B1 (mouse: Pafah1b1) gene and is characterized by brain malformation, developmental delays, and epilepsy. Here, we investigate the impact of Pafah1b1 mutation on the cellular migration, morphophysiology, microcircuitry, and transcriptomics of mouse hippocampal CA1 parvalbumin-containing inhibitory interneurons (PV+INTs). We find that WT PV+INTs consist of two physiological subtypes (80% fast-spiking (FS), 20% non-fast-spiking (NFS)) and four morphological subtypes. We find that cell-autonomous mutations within interneurons disrupts morphophysiological development of PV+INTs and results in the emergence of a non-canonical ‘intermediate spiking (IS)’ subset of PV+INTs. We also find that now dominant IS/NFS cells are prone to entering depolarization block, causing them to temporarily lose the ability to initiate action potentials and control network excitation, potentially promoting seizures. Finally, single-cell nuclear RNAsequencing of PV+INTs revealed several misregulated genes related to morphogenesis, cellular excitability, and synapse formation. *For correspondence: [email protected] Competing interests: The Introduction authors declare that no Excitation in neocortical and hippocampal circuits is balanced by a relatively small (10–15%) yet competing interests exist. -
Laboratory Testing for Her2 Status in Breast Cancer
Laboratory Testing for Her2 Status in Breast Cancer Katherine Geiersbach, M.D. Assistant Professor, Department of Pathology May 28, 2015 Overview • Clinical relevance of Her2 status for treatment of breast cancer • Standard approaches for determining Her2 status in breast cancer • Current concepts and controversies in Her2 testing 2 Who gets breast cancer? • Breast cancer is one of the most common malignancies to affect women • About 1 in 8 women will be diagnosed with breast cancer at some point in her lifetime • Most cases of breast cancer are sporadic, but a small percentage (5-10%) are related to a heritable gene mutation, most commonly BRCA1 or BRCA2 • Having a first degree relative with breast cancer increases a woman’s chance of developing breast cancer • Screening mammography is recommended for older women – US Preventive Services Task Force: Every 2 years starting at age 50 – American Cancer Society, others: Every 2 years starting at age 40 How is breast cancer treated? • Surgery: excision with or without sentinel lymph node biopsy – Breast conserving: lumpectomy, partial mastectomy – Mastectomy • Chemotherapy: before and/or after surgery • Radiation • Targeted therapies – Hormone therapy: Tamoxifen, aromatase inhibitors – Her2 targeted therapy for cancers with overexpression of the gene ERBB2, commonly called Her2 or Her2/neu • Treatment is based on testing for ER, PR, and Her2 status, as well as cancer grade and stage. 4 Her2 targeted therapy • Herceptin (trastuzumab) • Others: pertuzumab (Perjeta), T-DM1 (Kadcyla), and lapatinib (Tykerb) • Recent data shows that a combination of pertuzumab, trastuzumab, and docetaxel (PTD) improved progression free survival compared to patients who had only trastuzumab and docetaxel (TD)1,2 source: http://www.perjeta.com/hcp/moa 1. -
Identification of a Novel PAFAH1B1 Missense Mutation As a Cause Of
Brain & Development xxx (2018) xxx–xxx www.elsevier.com/locate/braindev Original article Identification of a novel PAFAH1B1 missense mutation as a cause of mild lissencephaly with basal ganglia calcification Chang-he Shi a,1, Shuo Zhang a,b,1, Zhi-hua Yang a,1, Yu-sheng Li a, Yu-tao Liu a, Zhuo Li a, Zheng-wei Hu a,b, Yu-ming Xu a,⇑ a Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000 Henan, China b Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China Received 14 April 2018; received in revised form 8 July 2018; accepted 17 July 2018 Abstract Purpose: To investigate the genetic and clinical features of a Chinese family exhibiting an autosomal dominant inheritance pat- tern of lissencephaly. Methods: Clinical examinations and cranial imaging studies were performed for all members of the family (two unaffected mem- bers and three surviving members from a total of four affected members). In addition, whole-exome sequencing analysis was per- formed for DNA from an affected patient to scan for candidate mutations, followed by Sanger sequencing to verify these candidate mutations in the entire family. A total of 200 ethnicity-matched healthy controls without neuropsychiatric disorder were also included and analyzed. Results: We identified a novel missense mutation, c.412G > A, p.(E138K), that cosegregated with the disease in exon 6 of the platelet activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1) gene in the affected members; this mutation was not found in the 200 controls. Multiple sequence alignments showed that codon 138, where the mutation (c.G412A) occurred, was located within a phylogenetically conserved region. -
Genetic Mosaic Dissection of Lis1 and Ndel1 in Neuronal Migration
Neuron Article Genetic Mosaic Dissection of Lis1 and Ndel1 in Neuronal Migration Simon Hippenmeyer,1,* Yong Ha Youn,2 Hyang Mi Moon,2,3 Kazunari Miyamichi,1 Hui Zong,1,5 Anthony Wynshaw-Boris,2,4 and Liqun Luo1,* 1Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA 2Department of Pediatrics and Institute for Human Genetics 3Biomedical Sciences Graduate Program 4Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research University of California, San Francisco School of Medicine, San Francisco, CA 94143, USA 5Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA *Correspondence: [email protected] (S.H.), [email protected] (L.L.) DOI 10.1016/j.neuron.2010.09.027 SUMMARY studied. Cortical layering occurs in an ‘‘inside-out’’ fashion whereby earlier born neurons occupy deep layers and succes- Coordinated migration of newly born neurons to their sively later born neurons settle in progressively upper layers (An- prospective target laminae is a prerequisite for neural gevine and Sidman, 1961; Rakic, 1974). Upon radial glia progen- circuit assembly in the developing brain. The evolu- itor cell (RGPC)-mediated neurogenesis, newborn migrating tionarily conserved LIS1/NDEL1 complex is essential cortical projection neurons are bipolar-shaped in the ventricular for neuronal migration in the mammalian cerebral zone (VZ) but then convert to a multipolar morphology within the cortex. The cytoplasmic nature of LIS1 and NDEL1 subventricular zone (SVZ) and migrate into the intermediate zone (IZ). A switch from the multipolar state back to a bipolar proteins suggest that they regulate neuronal migra- morphology precedes radial glia-guided locomotion of projec- tion cell autonomously. -
PAFAH1B1 Antibody Cat
PAFAH1B1 Antibody Cat. No.: 45-104 PAFAH1B1 Antibody 45-104 (3.75ug/ml) staining of paraffin embedded Human 45-104 (3.75ug/ml) staining of paraffin embedded Human Thyroid. Steamed Cortex. Steamed antigen retrieval antigen retrieval with citrate buffer Ph 6, AP-staining. with citrate buffer pH 6, AP- staining. 45-104 (3.75ug/ml) staining of paraffin embedded Human Pancreas. Steamed antigen retrieval with citrate buffer Ph 6, AP-staining. Specifications HOST SPECIES: Goat September 25, 2021 1 https://www.prosci-inc.com/pafah1b1-antibody-45-104.html SPECIES REACTIVITY: Human, Rat IMMUNOGEN: The immunogen for this antibody is: TGSVDQTVKVWECR TESTED APPLICATIONS: ELISA, IHC, WB Peptide ELISA: antibody detection limit dilution 1:32000.Western Blot:Approx 40kDa band observed in Human Ovary and in Rat Ovary lysates (calculated MW of 46.6kDa APPLICATIONS: according to Human NP_000421.1 and to Rat NP_113951.1). Recommended concentration: 0.1-0.3ug/ml.Immunohistochemistry:Paraffin embedded Human Brain (Cortex), Thyroid and Pancreas. Recommended concentration: 3.75ug/ml. SPECIFICITY: #To_Delete#. POSITIVE CONTROL: 1) Cat. No. 21-468 - Rat Ovary Lysate Properties Purified from goat serum by ammonium sulphate precipitation followed by antigen PURIFICATION: affinity chromatography using the immunizing peptide. CLONALITY: Polyclonal CONJUGATE: Unconjugated PHYSICAL STATE: Liquid Supplied at 0.5 mg/ml in Tris saline, 0.02% sodium azide, pH7.3 with 0.5% bovine serum BUFFER: albumin. Aliquot and store at -20°C. Minimize freezing and thawing. CONCENTRATION: -
Duplications of 17P FTNW
Duplications of 17p rarechromo.org 17p duplications A 17p duplication means that the cells of the body have a small but variable amount of extra genetic material from one of their 46 chromosomes – chromosome 17. For healthy development, chromosomes should contain just the right amount of genetic material (DNA) – not too much and not too little. Like most other chromosome disorders, having an extra part of chromosome 17 may increase the risk of birth defects, developmental delay and learning (intellectual) disability. However, the problems vary and depend on what and how much genetic material is duplicated. Background on Chromosomes Chromosomes are structures which contain our DNA and are found in almost every cell of the body. Every chromosome contains thousands of genes which may be thought of as individual instruction booklets (or recipes) that contain all the genetic information telling the body how to develop, grow and function. Chromosomes (and genes) usually come in pairs with one member of each chromosome pair being inherited from each parent. Most cells of the human body have a total of 46 (23 pairs of) chromosomes. The egg and the sperm cells, however have 23 unpaired chromosomes, so that when the egg and sperm join together at conception, the chromosomes pair up and the number is restored to 46. Of these 46 chromosomes, two are the sex chromosomes that determine gender. Females have two X chromosomes and males have one X chromosome and one Y chromosome. The remaining 44 chromosomes are grouped in 22 pairs, numbered 1 to 22 approximately from the largest to the smallest. -
Doublecortin Is Required in Mice for Lamination of the Hippocampus but Not the Neocortex
The Journal of Neuroscience, September 1, 2002, 22(17):7548–7557 Doublecortin Is Required in Mice for Lamination of the Hippocampus But Not the Neocortex Joseph C. Corbo,1,2 Thomas A. Deuel,1 Jeffrey M. Long,3 Patricia LaPorte,3 Elena Tsai,1 Anthony Wynshaw-Boris,3 and Christopher A. Walsh1 1Department of Neurology, Beth Israel Deaconess Medical Center, and Programs in Neuroscience and Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts 02115, 2Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts 02115, and 3Departments of Pediatrics and Medicine, University of California, San Diego School of Medicine, San Diego, California 92093 Doublecortin (DCX) is a microtubule-associated protein that is cal lamination that is largely indistinguishable from wild type required for normal neocortical and hippocampal development and show normal patterns of neocortical neurogenesis and in humans. Mutations in the X-linked human DCX gene cause neuronal migration. In contrast, the hippocampus of both het- gross neocortical disorganization (lissencephaly or “smooth erozygous females and hemizygous males shows disrupted brain”) in hemizygous males, whereas heterozygous females lamination that is most severe in the CA3 region. Behavioral show a mosaic phenotype with a normal cortex as well as a tests show defects in context and cued conditioned fear tests, second band of misplaced (heterotopic) neurons beneath the suggesting that deficits in hippocampal learning accompany cortex (“double cortex syndrome”). We created a mouse carry- the abnormal cytoarchitecture. ing a targeted mutation in the Dcx gene. Hemizygous male Dcx mice show severe postnatal lethality; the few that survive to Key words: doublecortin; knock-out; mouse; cerebral cortex; adulthood are variably fertile. -
N-Acetyl-D-Glucosamine Kinase Interacts with Nudc and Lis1 in Dynein Motor Complex and Promotes Cell Migration
International Journal of Molecular Sciences Article N-Acetyl-D-Glucosamine Kinase Interacts with NudC and Lis1 in Dynein Motor Complex and Promotes Cell Migration Md. Ariful Islam 1,†, Ho Jin Choi 1, Raju Dash 1 , Syeda Ridita Sharif 1,‡, Diyah Fatimah Oktaviani 1 , Dae-Hyun Seog 2 and Il Soo Moon 1,3,* 1 Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea; [email protected] (M.A.I.); [email protected] (H.J.C.); [email protected] (R.D.); [email protected] (S.R.S.); [email protected] (D.F.O.) 2 Department of Biochemistry, Dementia and Neurodegenerative Disease Research Center, Inje University College of Medicine, Busan 47392, Korea; [email protected] 3 Dongguk Medical Institute, Dongguk University College of Medicine, Gyeongju 38066, Korea * Correspondence: [email protected]; Tel.: +82-54-770-2414; Fax: +82-54-770-2447 † Current address: Departments of Biological Sciences & Brain and Cognitive Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. ‡ Current address: Department of Pharmacy, University of Science and Technology Chittagong, Chittagong 4202, Bangladesh. Abstract: Recently, we showed that N-acetylglucosamine kinase (NAGK), an enzyme of amino sugar metabolism, interacts with dynein light chain roadblock type 1 (DYNLRB1) and promotes the functions of dynein motor. Here, we report that NAGK interacts with nuclear distribution protein C (NudC) and lissencephaly 1 (Lis1) in the dynein complex. Yeast two-hybrid assays, pull-down assays, immunocy- tochemistry, and proximity ligation assays revealed NAGK–NudC–Lis1–dynein complexes around nuclei, at the leading poles of migrating HEK293T cells, and at the tips of migratory processes of cultured rat neuroblast cells. -
Neuronal Migration Genes and a Familial Translocation T (3;17)
Hadj Amor et al. BMC Medical Genetics (2020) 21:26 https://doi.org/10.1186/s12881-020-0966-9 RESEARCH ARTICLE Open Access Neuronal migration genes and a familial translocation t (3;17): candidate genes implicated in the phenotype Meriam Hadj Amor1,2, Sarra Dimassi1,3, Amel Taj4, Wafa Slimani1,2, Hanene Hannachi1, Adnene Mlika4, Khaled Ben Helel5, Ali Saad1,3 and Soumaya Mougou-Zerelli1,3* Abstract Background: While Miller-Dieker syndrome critical region deletions are well known delineated anomalies, submicroscopic duplications in this region have recently emerged as a new distinctive syndrome. So far, only few cases have been described overlapping 17p13.3 duplications. Methods: In this study, we report on clinical and cytogenetic characterization of two new cases involving 17p13.3 and 3p26 chromosomal regions in two sisters with familial history of lissencephaly. Fluorescent In Situ Hybridization and array Comparative Genomic Hybridization were performed. Results: A deletion including the critical region of the Miller-Dieker syndrome of at least 2,9 Mb and a duplication of at least 3,6 Mb on the short arm of chromosome 3 were highlighted in one case. The opposite rearrangements, 17p13.3 duplication and 3p deletion, were observed in the second case. This double chromosomal aberration is the result of an adjacent 1:1 meiotic segregation of a maternal reciprocal translocation t(3,17)(p26.2;p13.3). Conclusions: 17p13.3 and 3p26 deletions have a clear range of phenotypic features while duplications still have an uncertain clinical significance. However, we could suggest that regardless of the type of the rearrangement, the gene dosage and interactions of CNTN4, CNTN6 and CHL1 in the 3p26 and PAFAH1B1, YWHAE in 17p13.3 could result in different clinical spectrums. -
An In-Depth Analysis of the HER2 Amplicon and Chromosome 17
Rondón-Lagos et al. BMC Cancer 2014, 14:922 http://www.biomedcentral.com/1471-2407/14/922 RESEARCH ARTICLE Open Access Unraveling the chromosome 17 patterns of FISH in interphase nuclei: an in-depth analysis of the HER2 amplicon and chromosome 17 centromere by karyotyping, FISH and M-FISH in breast cancer cells Milena Rondón-Lagos1,4, Ludovica Verdun Di Cantogno2, Nelson Rangel1,4, Teresa Mele3, Sandra R Ramírez-Clavijo4, Giorgio Scagliotti3, Caterina Marchiò1,2*† and Anna Sapino1,2*† Abstract Background: In diagnostic pathology, HER2 status is determined in interphase nuclei by fluorescence in situ hybridization (FISH) with probes for the HER2 gene and for the chromosome 17 centromere (CEP17). The latter probe is used as a surrogate for chromosome 17 copies, however chromosome 17 (Chr17) is frequently rearranged. The frequency and type of specific structural Chr17 alterations in breast cancer have been studied by using comparative genomic hybridization and spectral karyotyping, but not fully detailed. Actually, balanced chromosome rearrangements (e.g. translocations or inversions) and low frequency mosaicisms are assessable on metaphases using G-banding karyotype and multicolor FISH (M-FISH) only. Methods: We sought to elucidate the CEP17 and HER2 FISH patterns of interphase nuclei by evaluating Chr17 rearrangements in metaphases of 9 breast cancer cell lines and a primary culture from a triple negative breast carcinoma by using G-banding, FISH and M-FISH. Results: Thirty-nine rearranged chromosomes containing a portion of Chr17 were observed. Chromosomes 8 and 11 were the most frequent partners of Chr17 translocations. The lowest frequency of Chr17 abnormalities was observed in the HER2-negative cell lines, while the highest was observed in the HER2-positive SKBR3 cells.