CH 3 Genetic Basis of Disease Flashcards
Gene, what is it and where is it located
fundamental unit of DNA, basic unit of heredity, located on the chromosome
Many disease processes are the result of
abnormal cell activity from alterations in the cells genetic control
genome refers to
the collection of all of an organisms genes
pharmacogenomics
study of gene function in health, disease, and the response to medications
Genetics
the study of inherited traits and patterns of inheritance
Genomics
the study of the interactions of all the nucleotide sequences (not just the genes) within an organism
A Nucleotide is
a combination of a pentose sugar, phosphate, and a purine or a pyrimidine nitrogen base
Nitrogenous bases and their pairs
Adenine to Thymine
Guanine to Cytosine
Adenine to Uracil
Exons
protein coding sequences
Introns
Non-coding sequences
Codon
an arrangement of three bases coding for one amino acid.
Mutation occurs when
a gene is damaged or changed in such a way that it alters the genetic code carried in the gene
The Human Genome is said to have between ____ and ____ genes
20 and 25 thousand
Polymorphisms
Common changes in a DNA sequence
Gametes
Germ cell, include sperm and ovum
Gene locus
location on the chromosome
Centromere
the narrowed point of the chromosome
P arm is ____
and Q arm is ____
P is short, Q is long
Karyotype
organized arrangement of all the chromosomes in a cell
Autosomes
genes related to body traits
RNA reads which way, prime ends?
3 prime to 5 prime
allele
the copy of the gene inherited from a parent
heterozygous
the gene from the mother is different than the gene from the father
homozygous
same gene variation from both mother and father
genotype
the set of genes inherited from mother and father, responsible for certain traits
phenotype
how a gene is manifested in an individual, expressed
Dominant
A gene that will be expressed even if the person only has one copy
Carrier
a person who is heterozygous for a recessive trait and does not manifest it but can pass it on.
autosomal
NON sex-linked traits
X allele is dominant?
True
Penetrance
refers to what percentage of people with the genotype will show the phenotype
Single Nucleotide Polymorphisms (SNPs)
one nucleotide substituted for another that may cause disease development and/or dysfunctional proteins. Ex: Sickle cell anemia is from an SNP
Inherited Mitochondrial disorders include: They are passed on by:
- neurogenerative disorders
- hypertrophic cardiomyopathy
- ophthalmoplegia
- maternally inherited deafness
- balance and sensation disorders (ataxia-neuropathy syndromes)
These disorders are passed on by the mother.
oncogene
a gene increasing the risk of cancer
proto-oncogenes
cells that control cell proliferation, mutation of these cells leads to activated oncogenes causing uncontrolled cellular proliferation or insuppressible cancerous growth
oncoproteins
defective proteins
tumor suppressor genes
genes that inhibit uncontrolled cellular mitosis and persistent proliferation. Defection of this gene means no suppression of cancerous transformation and growth of cells
Knudson’s __ ___ hypothesis
two hit
Knudson’s two hit hypothesis says
A person has an at risk gene on an allele and the gene on the other allele is mutated at some point during their lifetime and they develop a disease because now both alleles are compromised.
aneuploidy
alteration in anaphase of mitotic division and results in a different number of chromosomes
translocation
when a chromosome piece breaks off and joins a different chromosome
Most common chromosomal alteration
Down Syndrome
Most commonly tested proteins for maternal serum to check for disorders
- alpha-fetoprotein (AFP)
- human chorionic gonadotropin (hCG)
- unconjugated estriol (uE3)
- dimeric inhibin A (DIA)
Chorionic Villus Sampling
diagnostic procedure to find chromosome abnormalities, some inherited disorders, and certain birth defects in a fetus, commonly offered to women over 35 (advanced maternal age)
Amniocentesis can detect __ of fetal chromosome abnormalities
99%
Marfan Syndrome,
mutation on what gene and chromosome,
contains the code for what
Fibrillin-1 gene on chromosome 15, contains the code for the glycoprotein fibrillin
Fibrillin is what, deficient in what syndrome
connective tissue found in heart valves, airways, and other tissues, deficient in Marfan’s Syndrome
Marfan’s signs and symptoms
- Sudden dyspnea with pneumothorax
- Sudden chest pain with aortic dissection
- Lower back pain in tailbone with spinal dura involvement
Marfan’s Syndrome Physical Findings
- Tall, lanky appearance
- Elongated arms and fingers
- Heart murmur from aortic regurgitation or mitral prolapse
- aortic dissection
- dysrhythmia
- Dyspnea, severe palpitations, and substernal pain in severe pectus excavatum
- Spontaneous pneumothorax
- pectus excavatum
- ligament hypermobility
- kyphoscoliosis
- Burning sensation and numbness or weakness in the legs because of dura mater defects
- Joint pain (adult patients)
- Visual problems
Marfan Syndrome - Dominant or Recessive
Autosomal Dominant
Marfan’s Syndrome Treatment
for symptoms and multiple conditions from defect
Marfan’s Syndrome Diagnostic Testing
- chest x-ray
- aortic angiogram
- echocardiogram
- CT
- MRI
- Genetic Testing
Cystic Fibrosis (CF) most common ethnicity
most common lethal inherited disease in persons of European ancestry
Cystic Fibrosis defective where, what chromosome for what
Defects in the CFTR gene, Gene 7, which encodes for a protein that functions as a chloride channel and regulates the flow of other ions across the surface of epithelial cells.
Cystic Fibrosis chiefly affected organs
respiratory system and pancreas. Excessive mucus and thickened secretions form plugs.
Cystic Fibrosis Signs and Symptoms
- Chronic cough
- upper respiratory infections
- GI disturbances caused by pancreatitis
- cirrhosis of the liver
- gallstones
Cystic Fibrosis Physical Findings
- Pulmonary wheezes
- rhonchi
- excess mucus in sputum
- sinusitis
- nasal polyps
- abdominal pain caused by pancreatitis and cholecystitis
- cirrhosis of the liver
- rectal prolapse
Cystic Fibrosis Diagnosis
- Genetic testing
- IRT, pancreatic protein, elevated
- QPIT, sweat test for chloride content
- Chest x-ray
- abdominal x-ray
- chest CT
- abdominal ultrasound
Cystic Fibrosis Treatment
- pancreatic enzyme supplements
- bronchodilators
- mucolytics
- nebulizer treatments
- antibiotics
- anti-inflammatory medications
Tay Sachs - Dominant or recessive
recessive
Tay Sachs Disease, defective on what chromosome, what enzyme is affected, and allows…
Mutation on chromosome 15. The lysosomal enzyme, hexosaminidase A, is severely deficient, which allows ganglioside to accumulate in tissues, particularly the brain and spinal cord.
Tay Sachs Disease Signs and Symptoms, development and aging
- lethargy and cognitive impairment
- infant appears normal until 6 months
- death usually occurs by age 3
Tay Sachs Disease Physical Findings
- as infant matures, motor coordination, lethargy, muscle flaccidity, and increasing cognitive impairment become apparent
- poor suck reflex in infant
Tay Sachs Diagnosis
- Genetic Testing
- cherry red spot” in eye
Tay Sachs Treatment
Treatment of symptoms and multiple conditions from disease
G6PD Deficiency,
All mutations that cause G6PD deficiency are found at the gene locus Xq28. A metabolic enzyme involved in RBC metabolism. NADPH, protecting RBCs against
Some of the RBCs undergo hemolysis when the body is under stress.
G6PD Deficiency - Dominant or Recessive
X linked recessive
G6PD Deficiency signs and symptoms
hemolysis that presents as jaundice
G6PD Deficiency Diagnosis
- Blood levels of G6PD
- bilirubin level,
- CBC
- measuring hemoglobin in the urine
- haptoglobin level
- LDH test
- methemoglobin reduction test
- reticulocyte count.
G6PD Treatment
- Periods of hemolysis and jaundice do not require treatment and will resolve on their own
- Avoid drugs and foods that cause hemolysis.
- Blood transfusions may be necessary for severe hemolysis. Possibly removal of the spleen.
- Folic acid should be given because the body is in a state of high RBC synthesis.
Down Syndrome what gene link
Trisomy 21, aneuploidy
Down Syndrome Signs and Symptoms
- Delay in developmental milestones.
- Congenital heart defects are common: dyspnea, cyanosis, and syncope (fainting) can result.
- Esophageal and intestinal complications are also common, (40%) which can cause problems with swallowing and malabsorption.
- 10-20 fold increase in risk of developing leukemia
- weak immune system
- susceptible to alzheimer’s
Down Syndrome Physical Characteristics
- Infant has facial features that are distinctive for Down syndrome.
- Flat facial profile.
- Oblique palpebral fissures and epicanthic folds around the eyes.
- Heart murmur.
- Cyanosis.
- Dyspnea.
- Approximately 80% of children have IQ of 25 to 50. The remaining 20% have normal or near-normal intelligence.
Down Syndrome Diagnosis
- Genetic Testing
- -amniocentesis
- -PUBS
- -Chorionic Villus Sampling (CVS)
- extraction of fetal cells from maternal circulation (blood test)
- Echocardiogram
- chest x-ray
- abdominal x-ray
Down Syndrome Treatment
treatment of symptoms and treatment of multiple conditions resulting from defect
Huntington’s Disease, defect in what chromosome, for what
Genetic defect at 4p16.3, called the huntingtin gene.
The gene defect causes a part of DNA called a CAG repeat sequence to repeat many more times than it should and form the huntingtin protein. associated with degeneration of specific neurons in the basal ganglia and cortex.
Huntington’s, Dominant or Recessive
Autosomal-dominant inherited disorder
Huntington’s Disease Signs and Symptoms
- Lack of control of movements, called chorea
- Cognitive decline, depression and psychosis possible
- Dementia late in the course of the disease
Huntington’s Disease Physical Characteristics
- Muscle spasticity
- Difficulty with speech and swallowing
- Subtle, tic-like movements may progress to flailing-type movements
- Lack of movement, blank face, tremor, rigidity
- Eventual akinesia (lack of any movement) occurs
Huntington’s Disease Diagnosis
Genetic testing, inheritance pattern, and clinical picture to make diagnosis. No imaging shows deterioration well.
Huntington’s Disease Treatment
- May benefit from Parkinson-type treatment of levodopa and dopamine agonists
- antidepressants may be necessary
- antipsychotics may be necessary
- anticonvulsants may be necessary
