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GENETICS – RESEARCH AND ISSUES G M ENE UTATIONS C E AUSES AND FFECTS No part of this digital document may be reproduced, stored in a retrieval system or transmitted in any form or by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in rendering legal, medical or any other professional services. G – R I ENETICS ESEARCH AND SSUES Additional books and e-books in this series can be found on Nova’s website under the Series tab. GENETICS – RESEARCH AND ISSUES G M ENE UTATIONS C E AUSES AND FFECTS HELENA M. CHRISTOFFERSEN EDITOR Copyright © 2020 by Nova Science Publishers, Inc. All rights reserved. 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Title: Gene Mutations: Causes and Effects Description: New York: Nova Science Publishers, [2019] | Series: Genetics – Research and Issues | Includes bibliographical references and index. Identifiers: LCCN 2019957063 (print) | ISBN 9781536169843 (paperback) | ISBN 9781536170306 (adobe pdf) Published by Nova Science Publishers, Inc. † New York CONTENTS Preface vii Chapter 1 Types of Gene Mutations and Their Mechanisms 1 Mehmet Buyukleyla, Eyyup Rencuzogullari, Muhsin Aydin and Mehmet Arslan Chapter 2 Gene Mutations of Hereditary Motor Neuron Diseases 59 Haruo Shimazaki Chapter 3 ESR1 Gene Amplification in Breast Cancers Is an Effort for DNA Stabilization and a Consequential Tumor Response 87 Zsuzsanna Suba Index 119 Related Nova Publications 125 PREFACE A gene is a DNA sequence that can be transcribed into an RNA molecule and transferred to offspring organisms. Changes in DNA sequences that determine the structure and function of a gene are called mutations. Gene Mutations: Causes and Effects opens by exploring the physical, chemical, and biological agents that cause mutations interact with DNA, leading to genetic instability. Recent advances in next-generation sequencing have led to the discovery of new causative genes or those mutations. The authors describe the phenotypes and gene mutations, discussing genotype-phenotype correlations compared with previous reports. Lastly, one study analyses all conflicting data concerning the amplification of the ESR1 gene, particularly its ambiguous prevalence in both untreated tumors and tumors either responsive or unresponsive to antiestrogen therapy. Chapter 1 - The DNA molecule is a very stable molecule, responsible for the execution of all biological functions in our cells. Thanks to this stability, genetic information is transmitted to the offspring in a correct way for generations. Gene is a DNA sequence that can be transcribed into an RNA molecule and transferred to offspring organisms. Changes in DNA sequences that determine the structure and function of a gene are called mutations. Mutations can be in protein-encoding sequences or in transcription-regulating sequences (promotor, enhancer, silencer, insulator, viii Helena M. Christoffersen UTR, etc.). Physical, chemical, or biological agents that cause mutations interact with DNA, leading to genetic instability. Mutations can be harmful, beneficial or neutral to the organism by causing the DNA sequence to acquire a new function or to lose the function of the gene. Most mutations are known to have deleterious effects and are the source of many diseases and disorders (cancer, hemoglobinopathies, Werner syndrome, Parkinson’s disease, Huntington’s disease, Xeroderma pigmentosum, etc.). Mutations increase the occurrence of genetic variations in populations and may lead to a stronger adaptation of the organism to the changing environment than others (e.g., the Δ32 mutant in the human CCR5 gene does not catch AIDS). Neutral mutations that do not alter the function of the protein cause polymorphisms by creating silent genetic alterations. These polymorphisms can also give an advantage to living things in the evolutionary process. Chapter 2 - Hereditary motor neuron diseases can be grouped into three categories. Those with upper motor neuron involvement are called hereditary spastic paraplegias (HSP), those with lower motor neuron involvement are referred to as spinal muscular atrophy (SMA), distal hereditary motor neuropathy (dHMN), Charcot-Marie-Tooth disease (CMT), and those with combined upper and lower motor neuron involvement are designated as familial amyotrophic lateral sclerosis (FALS). They are caused by mutations in the various genes. Recent advances in next-generation sequencing have discovered new causative genes or those mutations. The authors could identify several gene mutations in HSP, CMT, and FALS families using whole-exome or genome sequencing. In this review, the authors described the phenotypes and gene mutations and discussed genotype-phenotype correlations compared with previous reports. Chapter 3 - The reported amplification of the estrogen receptor alpha gene (ESR1) in breast cancers initiated a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic alteration. The presented study analyses all conflicting data concerning the amplification of ESR1 gene; its ambiguous prevalence in both untreated tumors and tumors either responsive or unresponsive to antiestrogen therapy. The fact will be highlighted that in healthy breast cells, the