Preface

The field of medical genetics and genomics is undergoing a constant revolution based on new breakthroughs that bring increasing insights into the etiology of rare and common diseases, which help improve the health care of individuals with these disorders.

The development of high-throughput technologies such as next-generation sequencing (NGS) has enabled the detection of inherited susceptibilities and actionable mutational profiles of tumors for tailored therapies and management. Additionally, the generation of such massive amounts of data has prompted advances in the field of bioinformatics, with regard to complex tools and numerous databases to guide the interpretation of such big data, and to deal with noninformative results such as the notorious variants of uncertain significance. Besides these technical challenges, important ethical issues must also be considered: for example, the disclosure of results from prenatal and newborn screening through NGS, and findings from population-level screening of asymptomatic individuals. Addressing such challenges is not easy. We propose that investigators must provide tentative answers for one vital question: What is the analytic validity, clinical validity, and clinical utility of genetic testing?

This book aims to depict some of the myriad applications of genetics and genomics in the practice of medicine. We present the material in three sections: (1) an introductory landscape of medical genetics and genomics and portraits of personalized genomic medicine; (2) the field of reproductive genetics and prenatal screening: the first two chapters of this section deal with the most critical factors involved in the success of embryo implantation through assisted reproductive technology, including endometrial receptivity and rates of embryonic aneuploidy; the third chapter evaluates the accuracy of invasive and noninvasive prenatal screening for predicting the risk of fetal malformations; and (3) the area of hereditary cancer genetics, wherein is presented an updated review of the clinical utility of genetic testing, as exemplified by the description of hereditary breast and ovarian cancers.

Even though the information presented here offers a very limited look at the modern-day developments and breakthroughs of the centenarian field of medical genetics, this book nevertheless provides an important glimpse of the fascinating and challenging era of personalized or precision medicine.

> **Israel Gomy** Universidade Federal do Paraná, Curitiba, Brazil

**1**

Section 1

Introduction

Section 1 Introduction

**3**

**Chapter 1**

*Israel Gomy*

**1. Introduction**

ago its roots and beginnings came from.

area that it is sometimes believed.

and perhaps all areas of medicine.

disease—should also be included.

**2. Modern genomics in medicine**

Modern Medical Genetics

and Genomics in the Era of

Personalized/Precision Medicine

Modern medical genetics as a well-defined field of medicine has developed so fast since its origins half a century ago that we cannot bear in mind how long time

It can be argued that genetics overall was based on measuring the problems of human hereditary features and inherited diseases, since before the twentiethcentury acceptance of Mendelian laws of heredity. Thus, medical genetics, viewed from its broadest perspective, is perhaps the oldest area of genetics and not a recent

During the years, with developments in cellular and molecular biology, the field of medical genetics expanded from a small clinical subspecialty focused at describing a few rare hereditary disorders to a recognized medical specialty whose principles and approaches are essential parts of the diagnosis and management of many disorders, both common and rare. These genetic concepts and approaches are not restricted to any one medical specialty or subspecialty, as they permeate many,

The medical geneticist is usually a physician who works as part of a team of clinical providers, including many other physicians, nurses, and genetic counselors, to evaluate patients and their relatives for possible hereditary diseases. They characterize the patient (or proband) through analyses of personal and family history and physical examination; assess risk and possible modes of inheritance; indicate diagnostic testing; manage prevention, treatment, and surveillance; and participate

During the twentieth century, it gradually became clear that hereditary factors were implicated in many conditions and that different genetic mechanisms were involved. Virtually, any disease is the result of the interaction of genes and environment, but the relative influence of the genetic component may be large or small. Traditionally, genetic conditions have been classified into three categories: monogenic, chromosomal, and multifactorial disorders. However, it is becoming increasingly evident that the interplay of different genes (polygenic inheritance) is essential in disease and that an additional category—acquired somatic genetic

Improvements in all areas of medicine, mainly public health and therapeutics, resulted in modifying patterns of diseases, with improving recognition of the role

in communicating to other family members at risk for the disorder.

## **Chapter 1**
