Genetics and Advances in Genetic Knowledge – Study Notes

Overview

Genetics and advances in genetic knowledge inform diagnosis, treatment, and prevention. Key areas include pharmacogenomics, perinatal genetic care, genetic testing, and gene therapy.
Pharmacogenomics: study of genetic and genomic influences on pharmacodynamics and pharmacotherapeutics; aims to tailor drug therapy to individual genetic profiles.
Perinatal care has long incorporated genetic considerations; genetic testing and interventions affect pregnancy management and neonatal care.
This set of notes summarizes fundamental concepts in genome biology, inheritance patterns, chromosomal abnormalities, genetic evaluation and counseling, and nursing roles.

Genome, Genes, and Chromosomes

Genome: a person’s complete genetic blueprint; determines inherited traits and predispositions; includes coding and noncoding DNA; variations among individuals influence phenotype.
Genes: the basic units of heredity for all traits.
Genes are organized into long segments of DNA that occupy specific locations on chromosomes.
A chromosome: a long, continuous strand of DNA carrying genetic information.
Inheritance is governed by the transmission of genes on chromosomes; genotype interacts with environment to shape phenotype.

Karyotype and Chromosome Analysis

Karyotype: pictorial analysis of the number, form, and size of an individual’s chromosomes.
Common sources for karyotyping: white blood cells and fetal cells in amniotic fluid.
Chromosome numbering: chromosomes are numbered from largest to smallest: 1,2,\,\dots,\,22; sex chromosomes designated as X\,and\,Y.
Purpose: detect numerical and structural chromosomal abnormalities that may underlie congenital anomalies or developmental disorders.

Patterns of Inheritance (Mendelian and Non-Mendelian)

Mendelian or monogenic disorders include:
- Autosomal dominant inheritance
- Autosomal recessive inheritance
- X-linked inheritance (X-linked recessive and X-linked dominant)
Other patterns include multifactorial disorders and nontraditional inheritance.
These patterns help predict recurrence risk and guide genetic counseling.

Autosomal Dominant Inheritance

Definition: disease manifests with a dominant allele; affected individuals typically have at least one affected parent.
Pedigree characteristics: vertical transmission; both sexes affected; affected individuals may have affected offspring across generations.
Genotype notation (as depicted in slides): one normal allele (\n) and one dominant allele (D) can yield an affected person when at least one D is present.
Risk to offspring from an affected heterozygous parent (assuming the other parent is unaffected): the probability an child is affected is P( ext{affected}) = 0.5 (50%).
Important considerations: new mutations can contribute; penetrance and expressivity may vary.

Autosomal Recessive Inheritance

Definition: disease manifests when an individual has two recessive alleles; carriers have one normal allele and one recessive allele and are typically asymptomatic.
Carrier-parent cross example: Aa x Aa yields
- Affected (aa): P( ext{affected}) = 0.25
- Carrier (Aa): P( ext{carrier}) = 0.5
- Normal (AA): P( ext{normal}) = 0.25
Implications: two carrier parents have a 25% risk with each pregnancy; consanguinity increases the probability of shared recessive alleles.

X-Linked Inheritance

X-Linked Recessive Inheritance
- More common in males; females typically carriers.
- Maternal carrier and normal father scenario: mother genotype X^A X^a, father X^A Y.
- Sons: P( ext{affected son}) = 0.5 (receiving X^a from mother).
- Daughters: a mix of carriers or normal, depending on transmission; daughters from a carrier mother can be carriers (X^A X^a) or normal (rarely) (X^A X^A).
- Affected father transmits his mutated X to all daughters, making them carriers if mother is not affected; sons receive Y and are not affected via the paternal X.
X-Linked Dominant Inheritance
- Affected father transmits the condition to all daughters (since daughters inherit the father’s X chromosome), while sons inherit the Y and are typically unaffected by the paternal X-linked dominant allele.
- Affected mother transmits the allele to about 50% of offspring regardless of sex.
Clinical implications: pattern shows sex bias in affected individuals and informs recurrence risk.

Chromosomal Abnormalities

Abnormalities of chromosome number:
- Monosomies (loss of a chromosome)
- Trisomies (extra chromosome)
- Polyploidy (more than two complete chromosome sets)
Abnormalities of chromosome structure:
- Deletions (loss of a chromosome segment)
- Inversions (segment flips in orientation)
- Translocations (exchange of segments between non-homologous chromosomes)
Sex chromosome abnormalities also occur (e.g., Turner syndrome, Klinefelter syndrome, Triple X).
Detection via karyotyping and diagnostic genetic testing; implications for development, fertility, and perinatal management.

Genetic Evaluation and Counseling

Ideal timing: before conception (preconception) for planning and risk assessment.
Reasons for referral include a broad spectrum of maternal, paternal, and familial factors.

Indications for Genetic Counseling (Key Triggers)

Maternal age ≥ 35 years or older at birth.
Paternal age ≥ 50 years or older at birth.
Previous child, parents, or close relatives with inherited disease, congenital anomalies, metabolic disorders, developmental disorders, or chromosomal abnormalities.
Consanguinity or incest.
Pregnancy screening abnormalities: alpha-fetoprotein (AFP) abnormalities, triple/quadruple screen abnormalities, amniocentesis findings, or abnormal ultrasound.
Stillborn with congenital anomalies.
Two or more pregnancy losses.
Teratogen exposure (drugs, medications, radiation, chemicals, infection) or teratogen risk.
Concerns about genetic defects in specific ethnic or racial groups (e.g., higher risk for certain conditions like sickle cell disease in individuals of African descent).
Abnormal newborn screening results.
Couples with a family history of X-linked disorders.
Carriers of autosomal recessive or autosomal dominant diseases.
Child born with one or more major malformations in a major organ system.
Child with abnormalities of growth.
Child with developmental delay, intellectual disability, blindness, or deafness.

Nursing Roles and Responsibilities in Genetic Counseling

Begin preconception counseling and refer for further genetic information as needed.
Take a thorough family history.
Schedule genetic testing.
Explain purposes, risks/benefits of screening and diagnostic tests.
Answer questions and address concerns.
Discuss costs, benefits, and risks of health insurance, and potential risks of discrimination.
Recognize ethical, legal, and social issues; safeguard privacy and confidentiality.
Monitor emotional reactions after receiving information and provide emotional support.
Refer to appropriate support groups.

Ethical, Social, and Practical Implications

Privacy and confidentiality are critical given genetic information’s sensitivity.
Potential for discrimination in employment or insurance; advocate for protections and informed consent.
Informed decision-making requires clear communication of risks, benefits, and limitations of testing.
Equity of access to genetic services is a practical concern in diverse populations.

Real-World Relevance and Connections

Pharmacogenomics contributes to personalized medicine by aligning drug choice and dosing with genetic profiles.
Genetic evaluation and counseling support reproductive decisions, early diagnosis, and targeted interventions.
Understanding inheritance patterns helps families anticipate risks and plan pregnancies accordingly.
Ethical, legal, and social considerations shape policy development and clinical practice in genetics.

Summary of Key Notations and Probabilities

Autosomal dominant: P( ext{affected child}) = 0.5 for a heterozygous affected parent cross with an unaffected partner.
Autosomal recessive: P( ext{affected}) = 0.25,\, P( ext{carrier}) = 0.5,\, P( ext{normal}) = 0.25 when both parents are carriers.
X-linked recessive: sons of carrier mothers have a 0.5 chance of being affected; daughters have a 0.5 chance of being carriers (when father is unaffected).
X-linked dominant: affected fathers pass the condition to all daughters; affected mothers pass to roughly 50% of offspring.