Term
| X-linked recessive Hardy-Weinberg Equilibrium |
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Definition
Normal males = p, Affected males = q
Normal female = p^2, Carrier female = 2pq, Affected female = q^2 |
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Term
| Factors affecting Hardy-Weinberg Equilibrium |
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Definition
| Non-random mating, selection, heterozygote advantage, mutation rate, small population size, gene flow (migration) |
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Term
| Examples of heterozygote advantage |
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Definition
| Sickle Cell Anemia, both thalassemias, Glucose-6-Phosphate Dehydrogenase deficiency - evolutionary prssure to protect against malaria |
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Term
| Coefficient of inbreeding: Parent-child or brother-sister |
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Definition
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Term
| Coefficient of inbreeding: Brother-halfsister, Uncle-niece, Double 1st cousins |
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Definition
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Term
| Coefficient of inbreeding: Half uncle-niece, first cousins |
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Definition
| Share 1/8 genes, F = 1/16 |
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Term
| Coefficient of inbreeding: half 1st cousins, 1st cousins once removed |
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Definition
| Share 1/16 genes, F = 1/32 |
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Term
| Coefficient of inbreeding: second cousins |
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Definition
| Share 1/32 genes, F = 1/64 |
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Term
| Increased risk in consanguineous couples |
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Definition
| Depends on how closely related they are but cousin couples had only ~3% increased risk of genetic problems in many studies |
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Term
| Goals of Human Genome Project |
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Definition
| Identify all human genes, sequences of 3 billion basepairs, store info, improve data storage and analysis tools, transfer technologies to private sector, address ethical, legal and social issues |
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Term
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Definition
| Study complete set of chromosomal and extra-chromosomal DNA/RNA of organism, cel, organelle, virus |
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Term
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Definition
| Study total mRNA in cell or tissue as specific time point |
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Term
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Definition
| Study all proteins present in genome, cell, tissue, organism |
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Term
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Definition
| Unique chemical fingerprint of specific cellular processes, quantify small-molecule metabolite profiles in cell type or organism |
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Term
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Definition
| Compare SNPs to detect polymorphisms in population; determine disease susceptibility, drug therapy efficacy, forensic analysis, genetic linkage analysis, genotyping - identify genes whose expression varies among different versions of same cancer |
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Term
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Definition
| Map, align, analyze DNA and protein sequences, gene finding, predicting gene expression, protein-protein interactions, protein structure - common application is GWAS |
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Term
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Definition
| Identify all functional elements of human genome sequence - found majority of genome used in some way (80%), not just tons of junk DNA |
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Term
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Definition
| Prohibit genetic information in health insurance and employment decisions, cannot exclude or charge higher premiums based on genetic predisposition to develop disease in future |
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Term
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Definition
Doesn't apply to life, disability and long-term care insurance
Doesn't apply if signs/symptoms of disease present and get diagnosis of genetic disease |
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Term
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Definition
| Genetic variation that alters the ability of the body to absorb, transport, metabolize, or excrete drugs - variations revealed solely by effects of drug |
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Term
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Definition
| Differentiate individuals with different responses to medications, optimize drug doses, identify those at risk for adverse drug reaction to avoid or modify treatment |
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Term
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Definition
| Develop new drugs from info from human genome and make profile to identify those at risk for at risk for adverse reaction |
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Term
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Definition
| Study genetically determined differences in susceptibility to action of physical, chemical, infectious agents in environment |
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Term
| Stages of drug intake important for pharmacogenetics |
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Definition
| Absorption in gut, protein binding in plasma, uptake by receptors or diffusion, interaction with target, breakdown and excretion, modification from prodrug to drug |
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Term
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Definition
| Determine the amount of drug in the system in different individuals at different time points to investigate patterns of drug effect |
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Term
| 3 types of variation in dose-response test for drug |
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Definition
Continuous variation - multifactorial, bell-shaped curve
Discontinuous bimodal - one stage is monogenic
Discontinuous trimodal - one stage is monogenic with codominant alleles |
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Term
| Nongenetic factors affecting influence of medication |
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Definition
| Route of drug administration, age, gender, organ function, body composition, drug interactions, diet |
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Term
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Definition
Need to know deficient protein or enzyme; limited to diseases where biochemical defect can be determined and protein isolated
Disease --> Function --> Gene --> Map |
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Term
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Definition
Need to understand the process: normal mechanism and all genes in pathway
Disease --> symptom analysis --> predict possible protein --> pick candidate gene --> see if allelic differences associate with disease |
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Term
| Positional and positional-candidate cloning |
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Definition
Disease --> Map --> Gene --> Function
Track phenotypic trait without knowing cause uderlying trait
DNA sample on family, find inheritance pattern, look for area with linkage to disease, sequence region, assess candidate genes |
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Term
| Determining if you have found disease-causing gene |
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Definition
| See if expressed in expected tissue pattern; see if only present in affected members of family; dissect role of gene in normal function; see how mutations affect gene and cause disease (genetically modified animals) |
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Term
| Use of microarray analysis on finding gene involved |
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Definition
| Allow researchers to track expression of new and unidentified genes in different tissues; look at differentially expressed genes in normal vs. cancer cells, e.g. |
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Term
| Disorders treatable by dietary restriction - need newborn screening |
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Definition
| Galactosemia, Maple Syrup Urine Disease, Phenylketonuria |
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Term
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Definition
| Elevated blood Phe potentially toxic to CNS, more in Caucasians, Northern European, need to start Phe-free formula in first 6 weeks to minimize IQ drop; potential teratogen if mother has it; secondary cause by THB deficiency (can supplement) |
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Term
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Definition
| Increased Galactose-1P levels, lead to hyperbilirubinemia, brain damage, cataracts, mortality from gram negative sepsis; treate with non-galactose formula in 1st 6 weeks, increased rate of premature ovarian failure with treatment |
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Term
| Maple Syrup Urine Disease |
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Definition
| BC ketoacidura due to lack of BCKAD - vomiting, poor feeding, irritable, turns to convulsions, coma, death; increased incidence in Mennonites, dietary restriction of BCAA (esp. Leu) with complicated formula, need early treatment or die in 3 months |
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Term
| Disorders where treatment includes substrate depletion |
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Definition
| Wilson Disease, Hemochromatosis, Arginosuccinic aciduria |
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Term
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Definition
| Inject solution into bloodstream to remove heavy metals or minerals, such as in Wilson Disease |
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Term
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Definition
| Disturbed copper metabolism, use trientine to prevent toxic effects on liver and brain; chelation or liver transplant in some cases |
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Term
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Definition
| Disorder of iron metabolism leading to progressive iron overload with toxic effects on liver, pancreas and joints age 30-40; monitor levels by periodic phlebotomy (blood draw) |
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Term
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Definition
| Present with hyperammonemia, administer arginine to make arginosuccinic acid that is non-toxic and readily excreted and benzoate and phenylacetate for alternate ways to excrete waste nitrogen - example of substrate depletion |
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Term
| Disorders where treatment includes supplementation with cofactor vitamins |
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Definition
| Homocystinuria and biotinidase deficiency |
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Term
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Definition
| Deficiency of cystathione beta-synthase - Marfan appearance with dislocated lenses, learning disabilities, propensity to thrombosis and claudication - half are aided by administration of pyridoxine (Vitamin B6) to decrease HCys levels |
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Term
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Definition
| Multiple carboxylase deficiency; hypotonia, seizures, rash, alopecia - treatable with daily oral biotin |
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Term
| Disorders where treatment includes treating with end-product |
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Definition
| Congenital Adrenal Hyperplasia, Hemophilias, Type I Gaucher Disease |
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Term
| Congenital Adrenal Hyperplasia |
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Definition
| Altered production of hormones of adrenal cortex, most commonly 21-hydroxylase deficiency, greater in Italians - virilization in females, electrolyte disturbance in males - treat with glucocorticoids; similarly GH used to treat GH deficiency |
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Term
| Hemophilia A and B treatment |
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Definition
| Use Factors VIII or pooled blood products (end-product) |
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Term
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Definition
| Recombinant enzyme targeted to macrophages, enzyme replacement therapy targeted to correct place to improve anemia and bone changes (only sufficient in non-neuronopathic form of disease) |
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Term
| Kidney allotransplant disorders |
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Definition
| Cystinosis, Nail-patella syndrome, Alport's syndrome, congenital nephritic syndrome, medullary cystic disease, familial polycystic disease (cystinosis is defect in transporting cystine out of lysosome) |
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Term
| Bone marrow allotransplant disorders |
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Definition
| Immunodeficiency and hematologic disorders, Sickle cell disease, beta-thalassemia |
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Term
| Liver autotransplant disorders |
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Definition
| Wilson's disease, hypercholesterolemia (combined with heart transplant) |
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Term
| Disorders decreaseing with primary prevention screening programs |
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Definition
| Tay-Sachs disease in Ashkenazi Jews, beta-thalassemia in Southern Italy; need to have parents accepting of approach (unlikely in CF or CAH) |
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Term
| Symptoms in Full Classic Cystic Fibrosis |
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Definition
| Chronic lung disease, male sterility, pancreatic insufficiency, increased sweat electrolytes (salty), Schanroth sign |
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Term
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Definition
| Clubbing of fingers, window between fingers is gone in patients with Cystic fibrosis |
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Term
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Definition
| Stop signal in CF gene too sign, no full CFTR made, complete absence of function |
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Term
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Definition
| CFTR misfolded, unable to reach right place in cell, most common - complete absence of function |
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Term
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Definition
| CFTR made and in right place but does not function - complete absence of function |
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Term
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Definition
| Faulty, narrowed opening in CFTR - partial loss of function |
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Term
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Definition
| CFTR made in smaller than normal quantities - partial loss of function |
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Term
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Definition
| CFTR degraded too quickly - partial loss of function |
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Term
| Reason for salty sweat glands in CF |
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Definition
| Impermeability to reabsorption of ions; different from effect in respiratory epithelial cell |
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Term
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Definition
| Replacement of defective or diseased cell population by transplantation of normal cells from unaffected donor (solid organ, bone marrow, embryonic stem cells) |
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Term
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Definition
| Transfer of genetic material into patient's cells to treat disease - replaced mutated gene with normal one, inactivate abnormal gene or introduce new gene |
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Term
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Definition
| Permanent modification of genes found in germ cells - impact all cells of developing embryo and pass on to next generation - ethically unacceptable to intentionally introduce new genetic material into humans (exception: mitochondrial disease) |
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Term
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Definition
| Modify genes only in somatic cells, not passed on to future generations, ex vivo or invov |
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Term
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Definition
Transfer of gene within individual to cells inside body - can access almost any site
Hard to control efficiency, high enough transfection without toxicity, possible dissemination of vector in body and contamination of germline |
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Term
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Definition
Remove cells, transduce in vitro, return to patient
Advantage: control which cells altered, high transduction efficiency
Disadvantage: hard to remove and re-engraft, only hematopoietic stem cells and cancer at this point |
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Term
| Challenges to safe delivery of DNA |
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Definition
| Efficiency of transfection, difficulty with large pieces of DNA (human genes large), robust inflammatory events, transient gene expression when no integration into host genome; random integration into genome can affect genes or cause cancer development |
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Term
| How to correct problem with insertion in gene therapy |
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Definition
| Gene augmentation (insert gene), gene inhibition (ribozyme, antisense oligo, siRNA, epigenetic silence), gene editing through CRISPR |
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Term
| Qualities of ideal vector for gene therapy |
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Definition
| High carrying capacity, ex vivo and in vivo usage, undetectable by immune system, safe to host, sufficient efficiency, long duration of expression or safe and easy readministration |
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Term
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Definition
| Naked DNA (injected, not integrated in host genome), DNA with gold particles (increase efficiency), liposomes (fuse with host cell, generally transient) |
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Term
| Nonviral vector advantages |
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Definition
| Transfect various different cells without need for interaction with specific receptors, minimal immunogenicity, high capacity, easy to produce |
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Term
| Nonviral vector disadvantages |
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Definition
| Low efficiency, transient DNA expression, can be inflammatory/immune reactions |
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Term
| Retroviral vector function |
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Definition
| Bind surface envelope protein or receptor, reverse transcribe, enter nucleus, randomly integrate into host genome - need replication defective modification of virus |
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Term
| Retroviral vector advantages |
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Definition
| High efficiency, long-term expression due to integration into host DNA |
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Term
| Retroviral vector disadvantages |
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Definition
| Size limitation, random integration (cancer), most affect rapidly dividing cells, long-term expression |
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Term
| Adenoviral vector function |
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Definition
| Bind to receptor, internalize in endosome, translocate to nucleus, start expression as episomal, replication occurs |
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Term
| Adenoviral vector advantages |
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Definition
| High packaging potential, highly efficient, dividing and nondividing cells, low risk of insertional mutagenesis, transient expression |
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Term
| Adenoviral vector disadvantages |
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Definition
| Transient expression, high doses toxic, immunogenicity prevents repetitive treatments, 70% population has neutralizing antibodies |
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Term
| Achondroplasia inheritance |
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Definition
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Term
| Cystic Fibrosis inheritance |
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Definition
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Term
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Definition
| Autosomal dominant and recessive |
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Term
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Definition
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Term
| Huntington disease inheritance |
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Definition
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Term
| Neurofibromatosis I inheritance |
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Definition
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Term
| Sex development disorder inheritance |
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Definition
| Y-linked or translocation |
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Term
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Definition
| Chromosomal microdeletion, de novo or translocation |
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Term
| Angelman Syndrome inheritance |
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Definition
| Chromosomal microdeletion, uniparental disomy |
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Term
| Autism 16.11.2 deletion Syndrome inheritance |
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Definition
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Term
| Beckwith-Wiedemann Syndrome inheritance |
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Definition
| Imprinting defect, uniparental disomy |
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Term
| CHARGE Syndrome Inheritance |
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Definition
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Term
| Fragile X Syndrome Inheritance |
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Definition
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Term
| Osteogenesis imperfecta inheritance |
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Definition
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Term
| Prader-Willi Syndrome inheritance |
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Definition
| Chromosomal microdeletion, uniparental disomy |
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Term
| Xeroderma pigmentosum inheritance |
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Definition
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Term
| Charcot-Marie-Tooth Disease inheritance |
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Definition
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Term
| Duchene Muscular Dystrophy inheritance |
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Definition
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Term
| Holoprosencephaly inheritance |
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Definition
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Term
| Myoclonic Epilepsy with ragged red fibers inheritance |
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Definition
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Term
| Myotonic Dystrophy inheritance |
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Definition
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Term
| Rett Syndrome Inheritance |
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Definition
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Term
| Spinal muscular atrophy inheritance |
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Definition
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Term
| G6PD deficiency inheritance |
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Definition
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Term
| MCAD Deficiency inheritance |
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Definition
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Term
| OTC Deficiency inheritance |
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Definition
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Term
| Phenylketonuria inheritance |
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Definition
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Term
| Polycystic kidney disease inheritance |
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Definition
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Term
| Thiopurine S-methyltransferase deficiency inheritance |
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Definition
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Term
| Type I Gaucher Disease inheritance |
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Definition
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Term
| Charcot-Marie-Tooth Disease |
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Definition
| Progressive distal muscle weakness, distal muscle wasting, hyporeflexia, segmental demyelination, myelin sheath hypertrophy; problem with recombination between tandem repeat elements |
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Term
| Duchene Muscular Dystrophy |
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Definition
| Muscle weakness, calf pseudo-hypertrophy, elevated serum creatine kinase; changes often at CpG repeats; high frequency of new mutations |
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Term
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Definition
| Ventral forebrain maldevelopment, facial dysmorphism, developmental delay, SHH mutation; often death before birth; can be single eye in middle of head |
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Term
| Myoclonic Epilepsy with Ragged Red Fibers |
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Definition
| Myopathy, dementia, myoclonic seizures, ataxia, deafness; reduce charged tRNA lys in mitochondria; need to exceed threshold |
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Term
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Definition
| Progressive muscle wasting and weakness, prolonged contractions, locking of jaw, infertility in men, cataracts, cardiac arrhythmia; expansion of trinucleotide repeat in non-coding region of gene |
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Term
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Definition
| Acquired microcephaly, neuro-developmental regression, repetitive stereotypic hand movements; inappropriate activation of target genes; neurons smaller and more densely packed |
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Term
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Definition
| Progressive hypotonia, more proximal muscle weakness; mutation in survival motor neuron gene which causes apoptosis to continue in fetus, progressive degeneration of alpha neurons in anterior horn of spinal cord |
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Term
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Definition
| Hemolytic anemia; neonatal jaundice; insufficient reduced glutathione during times of oxidative stress |
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Term
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Definition
| Hypoketotic hypoglycemia, vomiting, lethargy, hepatic encephalopathy; accumulation of dicarboxylic acids since can't break down fatty acids past MCFA |
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Term
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Definition
| Neonatal onset; hyperammonemia, coma; males more severely affected since hemizygous; mosaic females due to random X inactivation |
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Term
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Definition
| Intellectual disabilities, hyperactivity, musty odor in breath, skin or urine, lighter skin, hair and eye color; buildup of phenylalanine in the blood |
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Term
| Polycystic kidney disease |
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Definition
| Progressive renal failure, renal and hepatic cysts |
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Term
| Thiopurine S-Methyltransferase deficiency |
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Definition
| Requires drug exposure, leads to myelosuppression, increased risk for brain tumor when receiving radiation in ALL |
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Term
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Definition
| Hepatosplenomegaly, anemia, thrombocytopenia, bone pain; deficiency of lysosomal beta-glucosidase; non-neuronal form is Type I |
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