Chapter 6

Genetics, Genomics, and Their Clinical Importance

• Genomics: 

  • The study of the entire genome, rather than only individual genes

• Genome: 

  • The complete set of genetic instructions found in a cell

• Shift from genetics to genomics: 

  • Sequencing the human genome expanded clinical attention from individual genes to interactions: 

• Clinical significance: 

  • Genetic and genomic tools help:

    • identify hereditary contributions to disease 

    • improve the ability to predict disease:

      • susceptibility

      • Onset

      • Progression

      • response to medications

• Precision or personalized medicine: 

  • Tailors prevention and treatment to the individual

• Epigenetics: 

  • Heritable changes in gene activity

    • caused by activation/deactivation of genes w/o changing DNA sequence

• Pharmacogenomics: 

  • Examines genetic differences influencing how medications are:

    • absorbed

    • move through the bod

    • metabolized

  • results may:

    • guide medication selection/dosing

    • reduce adverse reactions

Nursing Roles in Genetics and Genomics

• Foundational responsibility:

  • All nurses need working knowledge of genetics and genomics

    • pts frequently seek help understanding:

      • inherited risks

      • testing options

      • results

• Preconception care:

  • Review personal/family Hx

  • discuss carrier-testing options

  • identify individuals or couples who may benefit from genetic counseling before pregnancy

• Carrier testing:

  • Help pts understand screening intended to identify individuals carrying a gene variant that could be passed to children

    • even when carrier does not have condition

• Prenatal screening and testing

• Labor and birth care:

  • Anticipate specialized care needs when the pregnant patient or fetus has a known genetic condition.

• Newborn screening:

  • Support screening

  • identify possible genetic conditions

  • explains follow-up needs

  • coordinate care for the infant and family

• Specialty and ongoing care:

  • prevention

  • assessment

  • treatment

  • referral for conditions

    • hereditary breast and ovarian CA

    • Lynch syndrome

    • cystic fibrosis

    • sickle cell disease

    • Factor V Leiden

• Palliative care:

  • Support infants with life-threatening genetic conditions

  • provide compassionate, family-centered care

• Psychosocial support

• Patient autonomy:

  • Respect decisions to accept or decline screening, testing, or other interventions

Human Genome Project and Clinical Applications

• Definition:

  • A publicly funded international effort to map the complete human genome.

• Clinical impact:

  • Genome sequencing improved:

    • identification of disease-associated genes

    • expanded genetic-testing options

    • strengthened individualized risk assessment

    • supported more targeted care

• Family history remains important:

  • family Hx highly useful and cost-effective source of genetic information

    • reveals family relationships, health behaviors, and social context.

Human Genome Project and Clinical Applications - Prenatal screening and diagnostic options

• Maternal serum screening:

  • Listed as a prenatal screening option; this chapter does not explain the specific markers, timing, or interpretation.

• Fetal ultrasound:

  • Listed as a prenatal assessment option; this chapter does not provide the detailed genetic-screening procedure or interpretation.

• Amniocentesis:

  • Listed as a prenatal testing option; fetal cells in amniotic fluid can be used for chromosomal analysis, and cells obtained by amniocentesis can support prenatal microarray testing.

• Chorionic villus sampling / CVS:

  • Listed as a prenatal testing option; cells obtained through CVS can support prenatal microarray analysis.

• Additional options discussed:

  • Preimplantation testing, expanded carrier screening, cell-free fetal DNA screening, prenatal microarray, whole-exome sequencing, and whole-genome sequencing.

• Chapter limitation:

  • The supplied chapter names the four traditional prenatal tests but directs readers elsewhere for detailed descriptions; those additional details are not included here.

Human Genome Project and Clinical Applications - Predictive testing: an important distinction

• Presymptomatic testing:

  • Identifies a mutation associated with a condition expected to develop if the individual lives long enough; the chapter uses Huntington disease as an example.

• Predispositional testing:

  • Identifies an inherited mutation associated with increased disease risk but does not establish that the condition will definitely occur; BRCA1 and BRCA2 testing are examples.

Ethical, Legal, and Social Implications

• Privacy and confidentiality:

  • Genetic information can reveal sensitive details about a patient and biologic relatives; disclosure and access must be handled carefully.

• Genetic discrimination:

  • The chapter identifies concern about unfair use of genetic information in employment and insurance.

• Autonomy:

  • Patients and families should make their own decisions about whether to undergo testing after receiving understandable information and support.

• Informed consent:

  • Explain the purpose, potential benefits, limitations, uncertainties, and possible consequences of testing. Consent can be difficult when future outcomes or available treatments remain uncertain.

• Family implications:

  • A genetic result may have significance for relatives, creating difficult questions about whether and how inherited risks should be shared.

• False-positive results:

  • A test can suggest a condition that is not actually present, potentially producing anxiety or unnecessary interventions.

• False-negative results:

  • A test can miss a condition or risk, potentially creating inappropriate reassurance or delaying recommended surveillance.

• Access and fairness:

  • Cost, insurance coverage, rural location, and availability of trained specialists can limit access to genetic services.

• Cultural considerations:

  • Views about disability, pregnancy, medical intervention, and acceptable risk can differ among individuals and families; counseling should remain respectful and individualized.

• Nondirective counseling:

  • Provide accurate information and support without pressuring patients toward a particular reproductive, testing, or treatment decision.

Essential Genetics Vocabulary

• Chromosome:

  • A threadlike structure composed of DNA and containing many genes.

• Somatic cell:

  • A body cell that ordinarily contains 46 chromosomes, arranged as 23 pairs.

• Autosomes:

  • The 22 chromosome pairs that are not sex chromosomes.

• Sex chromosomes:

  • The remaining chromosome pair. The chapter designates a typical female karyotype as 46,XX and a typical male karyotype as 46,XY.

• Alleles:

  • Different versions of a gene located at corresponding positions on paired chromosomes.

• Homozygous:

  • Having two copies of the same allele for a particular trait, such as BB or bb.

• Heterozygous:

  • Having two different alleles for a particular trait, such as Bb.

• Important distinction:

  • XX and XY describe sex-chromosome combinations; they are not examples of homozygous and heterozygous allele pairs.

• Genotype:

  • An individual’s genetic makeup for a particular gene pair, such as Bb; the term can also refer more broadly to overall genetic makeup.

• Phenotype:

  • The observable expression of a genotype, such as a physical characteristic, biochemical trait, or other expressed feature.

• Dominant allele:

  • An allele expressed when only one copy is present; uppercase B can represent a dominant allele in a simplified inheritance example.

• Recessive allele:

  • An allele generally expressed when two copies are present; lowercase b can represent a recessive allele in a simplified autosomal inheritance example.

• Carrier:

  • An individual with one variant allele for a recessive condition who may pass that allele to offspring without necessarily expressing the condition.

• Karyotype:

  • An organized pictorial analysis of chromosome number, size, and shape used to identify chromosomal abnormalities.

• Diploid:

  • Containing two sets of chromosomes; most human somatic cells are diploid and have 46 chromosomes.

• Haploid:

  • Containing one chromosome set; human egg and sperm cells normally have 23 chromosomes.

Cell Division and Chromosomal Abnormalities

• Mitosis:

  • Division of somatic cells producing daughter cells with the diploid chromosome number.

• Meiosis:

  • Division involved in egg and sperm formation that reduces chromosome number to a haploid set.
    
    

• Why errors matter:

  • Mistakes during either mitosis or meiosis can produce abnormal chromosome numbers or structural changes affecting development, pregnancy outcomes, or reproductive function.

• Nondisjunction:

  • Failure of chromosomes to separate normally during cell division, potentially creating cells or gametes with an extra or missing chromosome.

• Mosaicism:

  • The presence of different cell populations within the same individual, such as some cells with a normal chromosome number and others with an extra or missing chromosome; may result from an early mitotic error.

Autosomal Abnormalities

• Definition:

  • Abnormalities involving the number or structure of autosomes

    • chromosome pairs 1 through 22

Autosomal Abnormalities - Abnormalities of chromosome number

• Euploidy:

  • The correct chromosome number for a cell, such as 23 chromosomes in a gamete or 46 in a typical somatic cell.

• Aneuploidy:

  • An abnormal number of individual chromosomes rather than an entire extra chromosome set.

• Monosomy:

  • One chromosome of a pair is missing; an affected cell commonly contains 45 total chromosomes.

• Trisomy:

  • An extra chromosome is present; an affected cell commonly contains 47 total chromosomes.

• Down syndrome:

  • Usually caused by trisomy 21; the chapter also describes translocation and mosaic forms.

• Other examples:

  • Trisomy 18 is Edwards syndrome, and trisomy 13 is Patau syndrome.

• Polyploidy:

  • An extra complete set or sets of chromosomes; the chapter gives triploidy with 69 chromosomes and tetraploidy with 92 chromosomes as examples.

• Maternal age relationship:

  • many trisomies arise from meiotic nondisjunction

  • likelihood of these errors increases with advancing maternal age

Autosomal Abnormalities - Abnormalities of chromosome structure

• Translocation:

  • Chromosomal material is exchanged between chromosomes

    • or moved from one chromosome to another

• Balanced versus unbalanced translocation:

  • A balanced rearrangement may not change the total amount of genetic material

  • an unbalanced rearrangement produces extra or missing material and may affect development or reproduction.

• Duplication:

  • An extra copy of a chromosomal segment is present.

• Deletion:

  • A segment of chromosomal material is lost.

• Microdeletion:

  • A very small deleted chromosomal segment that may require specialized testing for identification.

• Inversion:

  • A chromosome segment is rearranged in reverse order.

• High-yield distinction:

  • An extra or missing whole chromosome is a numerical abnormality

  • exchange, duplication, deletion, or reversal of a chromosome segment is a structural abnormality

Sex-Chromosome Abnormalities - Turner syndrome

• Chromosome pattern:

  • Monosomy X

    • written 45,X

    • one sex chromosome is missing

• Typical characteristics described:

  • Short stature, underdeveloped ovaries, juvenile external genitalia, a webbed neck, low posterior hairline, low-set ears, and swelling of the hands or feet.

• Associated concerns:

  • Heart defects, kidney problems, and infertility

  • many affected pregnancies miscarry spontaneously

Klinefelter syndrome - Klinefelter syndrome

• Chromosome pattern:

  • An extra X chromosome in a male, commonly written 47,XXY.

• Typical characteristics described:

  • small testes, reduced testosterone production, delayed or incomplete puberty, breast enlargement, reduced facial or body hair, and taller stature.

• Associated concerns:

  • Infertility, learning difficulties, and delayed speech or language

  • some individuals with mosaic Klinefelter syndrome may remain fertile

Patterns of Genetic Transmission

• Unifactorial / single-gene inheritance:

  • A trait or disorder is controlled primarily by a single gene

    • follows an identifiable inheritance pattern

• Multifactorial inheritance:

  • A trait or condition results from multiple genetic influences interacting with environmental factors

• Autosomal versus X-linked:

  • Autosomal conditions involve genes on chromosome pairs 1 through 22

  • X-linked conditions involve genes located on the X chromosome

• Dominant versus recessive:

  • Dominant traits generally require one variant allele for expression

  • recessive autosomal traits generally require two variant alleles

Patterns of Genetic Transmission - Autosomal recessive inheritance

• Mechanism:

  • Two disease-associated alleles, one inherited from each parent, are required for the condition to be expressed

• Carrier parents:

  • When both parents carry one affected allele, each pregnancy has:

    • 25% chance of an affected child

    • 50% chance of an unaffected carrier

    • 25% chance of a child with two unaffected alleles

• Family pattern:

  • The condition may appear among siblings

    • even when neither parent has symptoms

  • males and females are equally likely to be affected.

• Examples named in the chapter:

  • Sickle cell disease

  • cystic fibrosis

  • phenylalanine hydroxylase deficiency

  • galactosemia

  • fructosemia

• Independent pregnancies:

  • The probability applies separately to every pregnancy

  • previous affected or unaffected children do not change the single-gene recurrence probability

Patterns of Genetic Transmission - Autosomal dominant inheritance

• Mechanism:

  • One variant allele on an autosome is sufficient for the trait or disorder to be expressed

• Transmission risk:

  • When one heterozygous parent is affected and other parent is unaffected:

    • each pregnancy has 50% chance of inheriting variant allele

• Family pattern:

  • Often appears across successive generations

  • males and females can be affected

• Variation:

  • Severity can differ among affected relatives

    • new mutation may appear in someone w/o a known family Hx

• Examples named in the chapter:

  • Huntington disease

  • Marfan syndrome

  • neurofibromatosis

  • achondroplasia

  • Factor V Leiden

  • hereditary BRCA-related CA susceptibility

Cancer Genomics

• Oncogenes:

  • Altered forms of proto-oncogenes that encourage excessive cell growth

• Tumor suppressor genes:

  • Normally slow or regulate cell growth

    • harmful mutations remove these controls

      • similar to losing the brakes on cell division

Cancer Genomics - Hereditary breast and ovarian cancer: BRCA1 and BRCA2

• Clinical significance:

  • Harmful inherited BRCA1 or BRCA2 variants increase susceptibility to breast/ovarian CA

• Inheritance pattern:

  • BRCA-related hereditary CA susceptibility is autosomal dominant

  • affected parent has 50% chance of passing the variant to each child

• Risk is not certainty:

  • A positive BRCA result indicates increased CA susceptibility, rather than a guarantee that CA will develop

• Other associated CA:

  • BRCA-related variants may also increase risk for additional CA

    • including pancreatic and prostate CA

Cancer Genomics - Hereditary colorectal cancer

• Familial adenomatous polyposis / FAP:

  • An autosomal dominant condition, associated with:

    • harmful changes in the APC tumor suppressor gene

    • development of numerous colon polyps

• Lynch syndrome:

  • AKA hereditary nonpolyposis colorectal CA

  • autosomal dominant condition caused by harmful changes in DNA mismatch-repair genes

• Associated CA risks:

  • Lynch syndrome increases colorectal and uterine CA risk

    • can also increase risk for CAs of the stomach, small intestine, liver, gallbladder, urinary tract, brain, and skin

Sickle Cell Disease as an Inheritance Example

• What the chapter establishes:

  • Sickle cell disease is identified as an autosomal recessive genetic condition for which carrier screening and genetic counseling may be relevant.

• Carrier concept:

  • A person with one disease-associated allele may carry and pass on that allele without having the autosomal recessive condition.

• Two-carrier example:

  • When both parents are carriers, each pregnancy has:

    • 25% chance of an affected child

    • 50% chance of an unaffected carrier

    • 25% chance of a child w/o disease-associated allele

Genetic Assessment, Counseling, and Nursing Follow-Through

• Occurrence risk:

  • probability of a genetic condition occurring when a couple has not yet had an affected child

• Recurrence risk:

  • probability that a genetic condition will occur again after a previous affected pregnancy or child