Genetics Flashcards
1
Q
What is the nurse’s role in genetics and genomics?
A
- Assessment
- Identification
- Referral activities
- Education, care, support
2
Q
What are the 4 broad types of genetic disorders and diseases?
A
- Chromosomal anomalies (mutations)
- Mendelian single-gene disorders
- Polygenic/multifactorial disorders
- Other
3
Q
What are the 2 types of chromosomal anomalies?
A
- Abnormal number (genome mutation)
2. Abnormal structure (chromosome mutation)
4
Q
Euploidy
A
46 chromosomes
5
Q
Aneuploidy
A
Any # other than 46 chromosomes
6
Q
Monosomy
A
Deficiency of a chromosome
7
Q
Polysomy
A
Too many chromosomes
8
Q
Characteristics of abnormal number
A
- Disorders involving sex chromosomes are more common and less debilitating
- Loss of chromosome material is more serious than excess of material
- Nondisjunction during meiosis is usually the cause of abnormal number (can be meiosis I or II)
9
Q
What are 4 causes of abnormal structure?
A
- Deletion
- Duplication
- Inversion
- Translocation
- These alter the structure of individual chromosomes
10
Q
What are 2 types of mutations?
A
- Point mutation: substitution of a single base pair (may or may not change an amino acid)
- Frameshift mutation: addition of deletion of 1 or 2 nucleotides (changes reading frame so all codons after mutation are incorrect)
11
Q
What are 3 Mendelian single-gene disorder patterns of inheritance?
A
- Autosomal dominant
- Autosomal recessive
- X-linked
12
Q
Characteristics of autosomal recessive disorders
A
- Due to mutation of a recessive gene on an autosome
- Males and females are equally affected
- Unaffected individuals may transmit disease to offspring (carrier)
- May see delay of onset, incomplete penetrance, variable expressivity
- Examples: cystic fibrosis, sickle cell
- AA = normal, Aa = carrier, aa = affected
13
Q
Autosomal recessive: homozygous dominant and heterozygous parents
A
Offspring genotypes
- AA = 50% (normal)
- Aa = 50% (carrier)
- aa = 0% (affected)
14
Q
Autosomal recessive: heterozygous parents
A
Offspring genotypes
- AA = 25% (normal)
- Aa = 50% (carrier)
- aa = 25% (affected)
15
Q
Autosomal recessive: homozygous recessive and heterozygous parents
A
Offspring genotypes
- AA = 0% (normal)
- Aa = 50% (carrier)
- aa = 50% (affected)
16
Q
Characteristics of autosomal dominant disorders
A
- Due to mutation of dominant gene on an autosome
- Males and females equally affected
- Does NOT skip generations, affected individuals have an affected parent
- Unaffected individuals do not transmit disease (no carriers)
- Example: Huntington’s disease
- AA = affected, Aa = affected, aa = normal
17
Q
Autosomal dominant: homozygous dominant and heterozygous parents
A
Offspring genotypes
- AA = 50% (affected)
- Aa = 50% (affected)
- aa = 0% (normal)
18
Q
Autosomal dominant: heterozygous parents
A
Offspring genotypes
- AA = 25% (affected)
- Aa = 50% (affected)
- aa = 25% (normal)
19
Q
Autosomal dominant: homozygous recessive and heterozygous parents
A
Offspring genotypes
- AA = 0% (affected)
- Aa = 50% (affected)
- aa = 50% (normal)
20
Q
Autosomal dominant: homozygous recessive and homozygous dominant parents
A
Offspring genotypes
- AA = 0% (affected)
- Aa = 100% (affected)
- aa = 0% (normal)
21
Q
Characteristics of X-linked recessive disorders
A
- Seen more often in males (only have one X)
- Can skip generations via carrier female
- Never passed from father to son (because father passes Y to son)
- Passed from father to all daughters (daughters are affected or carrier)
- Example: Duchenne Muscular Dystrophy, Hemophilia A
22
Q
Polygenic traits
A
- Result from several genes acting together
- Example: height, weight, IQ
23
Q
Multifactorial traits
A
- Genes make individual susceptible
- Environmental factors may trigger susceptibility or influence expression of a trait
- Difficult to predict risk of occurrence but “runs in families”
- Example: Type 2 Diabetes, HTN
24
Q
Penetrance and Expressivity
A
Both terms quantify modification of gene expression by varying environmental and genetic background
25
Penetrance
- % in which gene is expressed
- % of individuals with a given genotype who exhibit the associated phenotype
- How something skips a generation
26
Expressivity
- Level of expression
- Extent of variation in phenotype associated with a particular genotype
- How environment and other genes are influential
- Differences among individuals with same disorder
27
Congenital
- Present at birth
- May or may not be hereditary
- De novo = from new, not hereditary
- Could be result of deviation in utero development
28
Hereditary
- Inherited genetically
29
Down Syndrome
- Individuals have an extra copy of chromosome 21 (trisomy 21)
- Most common chromosomal disorder
- Risk increases with maternal age
30
Down Syndrome Pathophysiology
- Nondisjunction (95%): pair of 21st chromosome fails to separate in meiosis
- Translocation (4%): full or partial copy of chromosome 21 attaches to another chromosome
- Mosaicism (1%): some cells have 46 chromosomes and some have 47
31
Down Syndrome Assessment
- Cognitive disability
- Low set ears
- Wide nasal bridge
- Protruding tongue (hypotonic)
- Upward slant to eyes, epicanthal folds
- Single palmar crease
- Small stature
- Nuchal changes (back of neck)
- Hypotonia
- Increased risk for: congenital heart disease, leukemia, respiratory
32
Down Syndrome Diagnosis
- Prenatal testing: screening, ultrasound (CHD and nuchal change), amniocentesis and chorionic villus sampling
- After birth: physical examination, karyotype
33
Down Syndrome Management
- Trends point toward longer life span
- Early developmental intervention
- Surgeries as needed
- Supportive interventions
34
Duchenne Muscular Dystrophy
- X-linked recessive
- Affecting only males
- Apparent by age of 3
35
Duchenne Muscular Dystrophy Pathophysiology
- Muscle cells are deficient in protein dystrophin (weak cell membrane)
- Leak creatinine kinase and take in calcium
- Proteases and inflammatory process are activated
- Leads to muscle fiber necrosis and muscle degeneration
36
DMD Clinical Manifestations
- Present with muscle weakness, difficulty walking
- Large calves (normal fiber replaced with fat and connective tissue)
- Gradual loss of ability to ambulate by 8-13 years
- Gower's sign: how they stand up
- Scoliosis
- Osteoporosis, fractures
- Muscle weakness progresses to respiratory weakness and premature death
37
DMD Diagnosis
- History and physical
- Elevated creatinine kinase initially
- Muscle biopsy
- Genetic testing
38
DMD Management
- Life expectancy: 20 years
- Goal is to maintain function and independence: surgery, bracing, physical therapy, prevent obesity, prompt attention to infection, steroid use
- Psychosocial support
39
Sickle Cell
- Autosomal recessive: aa = affected, Aa = carrier
- Chromosome 11
- Sickle cell disease: homozygous inheritance
- Sickle cell trait: heterozygous inheritance
- More common in African Americans or Mediterranean descent
- More common in parts of world where malaria is present and offers malaria protection
- Point mutation: changes hemoglobin stability and solubility
40
Sickle Cell Pathophysiology
- Genetic mutation causes defective hemoglobin molecule (Hb S)
- When O2 is low, Hb S undergoes polymerization and changes into sickled shape (RBCs don't travel well in bloodstream)
- Step 1: Sickling = occlusion of small arteries, tissue damage, pain
- Step 2: Anemia = shorter lifespan due to hemolysis, hyperbilirubinemia
41
Triggers for cells to sickle
- Dehydration
- Infection
- Fever
- Acidosis
- Hypoxia
- Exposure to cold
42
Sickle Cell Clinical Manifestations
- Symptoms typically don't present until 4-6 months of life bc fetal Hb is higher in O2
- Chronic anemia
- Pallor
- Jaundice
- Fatigue
- Delayed growth and puberty
- Infections: most common cause of death
43
3 types of sickle cell crisis
1. Vaso-occlusive
2. Acute sequestration
3. Aplastic anemia
44
Vaso-occlusive sickle cell crisis
- Sickled cells and vasospasm block blood flow
- Thrombosis and infarction
- Extremely painful
- Lasts days or weeks
- Potential locations: joint or bone pain, acute chest syndrome, dactylics, priapism, cerebrovascular
45
Acute sequestration sickle cell crisis
- Usually children 6 months - 4 years
- Blood pools cause enlargement
- Hypovolemic shock
- Emergency
- Potential locations: spleen (may remove), liver, lungs
46
Aplastic anemia sickle cell crisis
- Increased destruction or decreased production of hemoglobin
- Profound anemia
- Associated with viral infections, fever
47
Sickle Cell diagnosis
- Newborn screening
- History and physical
- Lab: anemia, sickled and target cells
48
Sickle Cell treatment
- Stem cell transplant
- Education to prevent sickling crisis (risk factors)
- Vaccinations
- Penicillin prophylaxis (even when not sick)
- Transfusions
- Splenectomy
- Pain management, hydration, oxygenation
49
Sickle Cell complications
```
Strokes, swelling, spleen
Infection, infarction
Crisis, chest syndrome, cardiac problems
Kidney disease
Liver and lung problems
Eyes/erection
```
50
Cystic Fibrosis
- Most common single-gene disorder
- Autosomal recessive: aa = affected, Aa = carrier
- Chromosome 7, 1300 different mutations
- Caucasian Americans
- Defect in membrane transporter for chloride ions in epithelial cells
- Production of abnormally thick secretions in glandular tissues
