Genetics and Molecular Biology in Nursing Practice

Module 1: 1 question - Nursing Scope of Practice: o Nurses must understand genetic principles to educate, advocate and assess patients and families o Responsibilities include taking family histories, recognizing genetic risk factors, and providing referrals to genetic specialists o Ethical responsibilities including maintaining confidentiality and informed consent Module 2: 5 questions - - - - DNA compositions: o Made of nucleotides (adenine, thymine, cytosine, guanine) forming a double helix Transcription to mRNA: o Identical sequence as the mRNA being produced but with U replacing T o The process of making an RNA copy of a gene DNA sequence Translation: o Involves the mRNA localizing to the ribosome and transfer RNA (tRNA) another type of RNA recognizing codons o mRNA is translated into proteins in the ribosomes Gene location: o Identified by chromosome number, arm (p or q), region, band, and sub -band Mutations: o Germ-line: occurs directly in sperm of egg or in a precursor cell that produces gametes; if mutant gamete participates in fertilization, then offspring will contain mutation o Somatic: cells of body effected; mutation can occur early or late stages of development; portion of body maintains mutation o Point: most basic mutation that can occur in DNA ▪ Involves a change in one base, at one point along the DNA sequence ▪ Some mutations involve more than one base of DNA ▪ Not all point mutations result in a change in protein o Missense: bases changes that result in an amino acid change ▪ May or may not be deleterious ▪ Example: sickle cell anemia • Val – His – Leu – Thr – Pro – Glu – Glu (normal) • Val – His – Leu – Thr – Pro – Val – Glu (sickled) o Nonsense: DNA base change can result in an amino acid being replaced by a stop codon ▪ Example: Duchenne muscle dystrophy and hemophilia o Frameshift: base or bases are inserted or deleted from DNA in group that are not a factor ▪ Example: Tay-Sachs o In-Frame: involves more than one base of DNA but does not change the reading frame ▪ Impacts the resulting protein by removing or adding one or more amino acids • Example: cystic fibrosis Nomenclature: the devising or choosing of names for things especially in a science or other discipline Module 3: 6 questions - Genotype: set of alleles that are present o Genetic composition of an individual Phenotype: observable physical traits produced by the actions of one or more gene -encoded proteins Inheritance patterns: o o o o - Triple o o Autosomal recessive: trait or condition that manifests only when the variant allele is present in a double dose (homozygous) ▪ Probability of having an affected child is 25% ▪ Probability of having an unaffected child who is homozygous for the normal allele is 25% ▪ Probability of having an unaffected child who is a carrier of the disease allele is 50% ▪ Punnett square: aa ▪ Characteristics: • Affected individuals generally have normal parents • Normal parents are carriers who transmit the mutation • Recurrence risk of offspring is 25% o 50% will be normal mutation carriers • Males and females are equally likely to be affected and transmit gene o Observe father to son transmission • May be multiple affected siblings but not in earlier generations appears to skip generations • Carriers may produce enough gene product and appear normal • Associated with founder effects and consanguinity Autosomal dominant: trait or condition that manifests in the heterozygous state, that is in a person possessing both variant allele and a normal allele ▪ Probability of having an affected child who has 1 copy of disease allele is 50% ▪ Probability of having child with 2 normal alleles is 50% ▪ Punnett square: Aa ▪ Characteristics: • Affected individuals generally have 1 affected parent • Does not skip generations • Males and females are equally likely to be affected or transmit the gene • Normal individuals do not transmit the gene X-linked recessive: manifests only in males ▪ All female offspring of affected males are carriers ▪ Sons have 50% of being affected even though it is recessive they will be affected ▪ Daughters 50% carriers and 50% normal ▪ Never transmits male to male ▪ If affected male marries heterozygous women there is a chance that 50% of sons will be affected giving erroneous impression of male-to-male transmission X-linked dominant: caused by mutation in gene on the X chromosome ▪ In females a mutation in one of the two copies of the gene in each cell is enough to cause the disorder ▪ In males a mutation in the only copy of the gene in each cell causes the disorder ▪ More affected females but males experience more severe symptoms than females ▪ No male-to-male transmission ▪ All daughters of affected males will be affected repeat disorders: Fragile X: ▪ Inheritance pattern: x-linked dominant ▪ Anticipation: phenotype of a genetic condition is expressed in greater severity and at earlier ages with successive generation ▪ Expansion: increase of triple repeat nucleotide sequence within gene Huntington’s: ▪ Inheritance pattern: autosomal dominant ▪ - Anticipation: symptoms appear earlier and are often more severe in successive generations ▪ Expansion: caused by CAG trinucleotide repeat expansion in the HTT gene; more repeats, earlier onset and worst disease Polygenic vs Multifactorial: o Characteristics: ▪ Greater the number of predisposing risk genes possessed by the parent the greater the probability that they will have an affected child ▪ Risk to relatives declines with increasingly remote degrees of relationships ▪ Recurrence risk is higher when more than one family member is affected ▪ Risk increases with severity of the malformation ▪ Where a multifactorial condition exhibits a marked difference in incidence with sex the less frequently affected sex has a higher risk threshold and transmits the condition more often to the more frequently affected sex o Multifactorial: involves bith genetic and environmental factors o Polygenic: more than one gene mutated and causing the disorder Module 4: 5 questions - Genetic testing: any test the result of which would prompt the health professional to alert the family members of potential risk o Diagnostic: confirm or rule out known suspected genetic disorder ▪ Individual is thought to be affected ▪ Test to confirm clinical impression o Predicitve: offered to asymptomatic individuals based on family history ▪ Presymptomatic: Huntington's ▪ Predispositional: breast cancer gene o - • New development in medicine • Individuals have no signs of disease • Wishes to know if they will develop it Carrier: to identify individuals who may have inherited an autosomal reccesive or x -linked recessive condition ▪ Condition will not affect individual ▪ The risk to affected offspring ▪ Examples: • Recessive or x-linked conditions • Cystic fibrosis • Duchenne muscular dystrophy o Prenatal: performed during pregnancy to assess health status of fetus; offered when there is increased risk ▪ Existing child has a genetic disorder ▪ Future pregnancies and risks o Newborn screening: identifies individuals who have increased chance of genetic condition so treatment can be started Karyotype: cab be performed on almost any tissue: amniotic fluid, blood, bone marrow, or placenta o Performed on lymphocytes arrested in metaphase, chromosomes arranged and analyzed by computer o Reveals monosomy, trisomy, large deletions and duplications, translocations and rearrangements o Noral results: 46 XX or 46 XY o - - - Some conditions under which tests may be performed: multiple birth defects, developmental delays, CML or other leukemias, ambiguous genitalia o FISH: uses DNA probes carrying a fluorescent label which hybridize specifically to known chromosome region o To identify targeted micro-deletions and duplications regions as small as 100,000 base pairs o Multiple FISH probes are used with FISH o Rapid FISH panel with probes directed at 13, 18, 21, X and Y, allows for 24 -hour diagnosis for timely management o Example: ▪ Down syndrome PCR: specific DNA sequences are copied many times to yield large quantities of that DNA, but shorter stretches of DNA analyzed o Need to know what area to amplify PKU: o What is happening: deficiency of phenylalanine hydroxylase ▪ Excess buildup of phenylalanine ▪ Deficiency of tyrosine o Signs and symptoms: ▪ Severe cognitive impairment ▪ Small stature ▪ Small head size ▪ Poor motor skills ▪ Light skin, hair and eye color ▪ Tremors and seizure activity ▪ Musty or mousy odor of sweat, breath and urine o Inheritance pattern: autosomal recessive - MSUD: o What is happening: potentially deadly disorder that affects breakdown of three amino acids: o leucine, isoleucine and valine ▪ They are normally broken down by six protein that acts as a team and form a complex called BCKD ▪ The most common defect is caused by a mutation in a gene on chromosome 19 that encodes the alpha subunit of the BCKAD complex Signs and symptoms: ▪ One of the earliest detected inborn errors due to maple syrup odor in urine ▪ o Newborn screen detects high levels of leucine ▪ Infants quickly demonstrate failure to thrive ▪ Neurologic symptoms begin 3-4 days after birth due to acidosis and hypoglycemia ▪ Flaccidity, hypertonicity, high pitched cry, opisthotonos posturing, cerebral edema ▪ Also milder forms with variability Inheritance pattern: autosomal recessive Module 5: 3 questions - Epigenetics: the study of heritable changes in phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence Genomic imprinting: certain genes are expressed in a parent-specific manner- meaning only the maternal or paternal copy is active while the other is silenced