Chapter 13

Carrier Screening

Introduction • Carrier screening involves testing of individuals for heterozygosity

for genes that would produce significant disorders in the homozygous state. Couples found to be at risk if both partners are carriers can be offered counseling regarding their options to deal with the risk.

• An individual may be at increased risk of being a carrier for a particular genetic trait on the basis of ancestry. Many screening programs are targeted toward particular groups known to be at risk.

• Couples found to be at risk have many options, including prenatal diagnosis, adoption, use of an egg or sperm donor, or planning for the medical needs of an affected child.

Introduction

• The decision to implement a carrier-screening program requires careful assessment of risks and benefits and provision of counseling, testing, and management resources. Carrier test results require careful interpretation and counseling of the couple.

• Genomic approaches are beginning to be applied to carrier screening, making it possible to significantly expand the scope of conditions for which screening is provided.

Chapter 14

Genetic Risk Assessment

Introduction

• Genome-wide association studies have revealed single-nucleotide polymorphisms (SNPs) in which specific alleles are associated with risk of various common disorders.

• Genotyping of individuals for specific SNPs can be used to estimate risk of disease, though the tests are not diagnostic.

Introduction

• Direct-to-consumer genome-wide genetic tests are available and provide information on risk of disease, carrier status for some recessive disorders, some pharmacogenetic traits, and information about some other common nonmedical phenotypes.

• Genetic tests for disease risk should be evaluated in terms of analytical validity, clinical validity, and clinical utility, as is the case for other genetic tests.

Genetic Screening for Disease Risk

• Presymptomatic tests apply to disorders that display age-dependent but complete penetrance, such as Huntington disease.

• An individual who tests positive will eventually develop the disorder if he or she lives long enough.

• The test is essentially deterministic of disease risk, though it may not predict time of onset or severity.

• A predispositional test can be used to estimate risk of disease but does not insure that an individual will or will not manifest the disorder.

• Predispositional tests apply to multifactorial traits, where multiple genes and/or environmental factors contribute to disease.

Genetic Screening for Disease Risk

Chapter 15

Genetic Test For Cancer Risk

Key Points

• Genetic predisposition to cancer is recognized by a pattern of familial transmission, as well as characteristics such as early age of onset and multifocality.

• A number of cancer predisposition syndromes have been identified, and some of these are subject to genetic testing.

Key Points

• A positive genetic test result for cancer predisposition can be helpful in planning a program of surveillance or institution of medical or surgical approaches to risk reduction. It can also provide a basis for genetic counseling of family members.

• Like all predispositional tests, cancer genetic test results must be interpreted with caution, since not all individuals will develop cancer, and there are both risks and benefits to being tested.