Question | Answer |
What is Q-banding? | Stain with quinacrine mustard (fluorescent). Bright Q bands correspond to dark G bands. Detects heteromorphisms of satellite repeats. |
What is G-banding? | Giemsa black stain most commonly used in karyotyping |
What is R-banding? | Heat the DNA before staining to improve resolution of bands. Reversed banding patterns. |
Metacentric Chromosome | arms are approximately equal length |
Submetacentric Chromosome | Centromere is off-center |
Acrocentric chromosome | Centromere near one end (13, 14, 15, 21, 22) |
Telocentric chromosome | only one arm (occurs sometimes w/chromosome rearrangements) |
What is C banding? | Stains centromere and constitutive heterochromatin only |
What is SKY? | Spectral karyotyping (uses 24 different colored fluorescent probes simultaneously) |
Heteroploid | any chromosome number other than 46 |
Euploid | Exact multiple of 23 chromosomes |
Aneuploid | Any chromosome number that is not a multiple of 23. Usually caused by nondisjunction. |
Triploidy & Tetraploidy | Embryonic Lethal, results from failure of complete cleavage of the zygote at an early stage |
Isochromosome | one arm is missing & the other is duplicated (haploinsufficiency of one arm and partial trisomy of the other). e.g. i(Xq) |
Paracentric Inversion vs. Pericentric Inversion | Para = 2 breaks occur in one arm to one side of the centromere, usually no change in phenotype. Peri = 2 breaks occur in one arm around the centromere, can lead to duplication and deficiency during meiosis. |
Balanced Reciprocal Translocation | Reciprocal exchange of broken-off segments between 2 different chromosomes. Very common, risk of abnormal progeny. Forms quadrivalent during meiosis. |
Robertsonian Translocation | 2 acrocentric chromosomes fuse near the centromere and lose short arms. (all acrocentric short arms contain repeats of ribosomal genes, so usually not deleterious). Risk of unbalanced progeny. |
Isodisomy vs. Heterodisomy | (= uniparental disomy), Isodisomy = 2 identical chromosomes from same parent, Heterodisomy = 2 nonidentical chromosomes from same parent |
Mole | When sperm fertilizes egg w/out nucleus. Develops into disorganized mass, can cause choriocarcinoma. |
Ovarian Teratoma | 46, XX containing only maternal chromosomes. Paternal --> extraembryonic devel. and maternal --> fetal devel. |
Supernumerary chromosome derived from a paracentromeric region | Typically has clinical repercussions |
Name the potential causes of Down Syndrome: | 1. Trisomy 21, 2. Robertsonian Translocation (46 chromosomes), 3. 21q21q Translocation (isochromosome origin), 4. Mosaic Down Syndrome, 5. Partial Trisomy 21 |
Marker Chromosome | Supernumerary chromosome, very small, risk of clinical disorder depend on genes in marker |
What are the 3 genetic disorders showing complete trisomy of an autonomic chromosome? | 21 (Down Syndrome), 18, and 13 |
47 XXY | Klinefelter syndrome (male). More X's = still Klinefelter, but more severe phenotype. paternal nondisjunction of meiosis 1. |
45 X | Turner syndrome (female), very uncommon (1/4000) short, webbed neck, cardiovascular abnormalities, normal intelligence |
What is the region of the sex chromosomes that undergoes recombination? | Pseudoautosomal. When recombination extends beyond this region, XX males and XY females can occur. |
X inactivation | X inactivation center at proximal Xq and XIST gene (only expressed from inactive X). X inactivation is usually random, but a damaged X is always inactivated. |
47 XYY | normal male phenotype (paternal nondisjunction at meiosis). slightly lower IQ, greater risk of ADHD & hyperactivity. paternal nondisjunction of meiosis 2. |
47 XXX | Trisomy X. Lower IQ, learning disabilities. 48XXXX & 49 XXXXX are more severe. |
Segmental Aneusomy | microdeletions producing haploinsufficiency for key genes |
What is the cell cycle in which most chromosome analysis is conducted? | Metaphase |
Name the 6 common indications for chromosome evaluation: | 1. Problems with early growth and development, 2. stillbirth and neonatal death, 3. fertility problems, 4. family history, 5. Neoplasia, 6. Pregnancy in woman of advanced age |
Which cell types are used in cell culture for FISH analysis? | Leukocytes & Lymphoblastoids (peripheral blood), fibroblasts (skin biopsy), bone marrow, fetal amniocytes or chorionic villus biopsy |
What are 3 identifying features of each chromosome? | 1. position of the centromere, 2. banding pattern, 3. size |
What are the chromosomal features & types of genetic testing available for fragile X? | 1. expose cells to chemicals that inhibit DNA synthesis, or 2. detect expansion of the CGG repeat in the FMR1 gene |
What are the 3 types of FISH probes? | 1. Locus-specific probes (look for presence/absence of particular genes), 2. repetitive DNA probes (detect satellite DNA/centromeres/telomeres), 3. whole chromosome probes (bind segmentally along length of chromosome: painting) |
What are the limitations of microarray CGH? | Measures relative copy number of DNA sequences, but not whether they have been translocated/rearranged |
What is the incidence of...(1) sex chromosome aneuploidy, (2) autosomal aneuploidy, (3) structural abnormalities ? | (1) sex chromosome aneuploidy 1/350 male -- 1/550 female, (2) autosomal aneuploidy 1/700, (3) structural abnormalities 1/375. TOTAL = 1/150 |
What are the chromosomal abnormalities leading to spontaneous abortion? | 1. Autosomal trisoym (0.52), 2. Autosomal monosomy (<0.01), 3. Triploidy (0.16), 4. Tetraploidy (0.06) |
Describe the difference between Prader Willi & Angelman Syndrome: | Prader Willi = lacking chromosome 15 from FATHER, Angelman = lacking lacking chromosome 15 from MOTHER |
What are the clinical features of Trisomy 18, 13, and 21 (besides mental retardation)? | Down Syndrome = loose neck skin, protruding tongue, heart disease. Patau Syndrome (Trisomy 13) = cleft palate, microcephaly, clenched hands, rocker-bottom feet, polydactyly. Trisomy 18 = cleft palate, clenched hands, receding jaw. |
Name two cytogenetic mechanisms for mosaicism: | mitotic event:
1. nondisjunction in an early postzygotic mitotic division, 2. trisomy of zygote that is lost in an early postzygotic division |
What is the mechanism of XX males and XY females? | SRY gene in sex determining region of Y chromosome (P11.3) is located right next to pseudoautosomal region |
What is the difference between recombination and sister chromatid exchange? | Meiosis recombination = exchange of different codes, Mitosis sister chromatid exchange = exchange of identical genetic code |
How can autosomal dominant be distinguished from X-linked dominant and pseudoautosomal dominant mutations? | X-linked dominant cannot be passed from father to son (son have an autosomal dominant-like pattern if recombination transfers X-linked genes to the Y chromosome (mostly female transmission with a few male) |
What is anticipation? | When a disease phenotype is expressed at earlier and earlier ages as it is passed from generation to generation. Common in unstable repeat expansion diseases. |
Fragile X Syndrome | fragile site on the q arm fails to condense during mitosis. 50% penetrance in females. Caused by an unstable repeat expansion. |
Mitochondrial genetic bottleneck | # mitochondria in the oocyte is severely reduced before being exponentially multiplied. This can allow a mutant mitochondrial DNA to dominate the gamete. |
Mitochondrial DNA mutations | each mitochondrion has multiple copies of DNA, but mutations can be propogated amongst daughter cells, and eventually produce homozygous cells. Inheritance is only from the mother. |
Obligate Heterozygote | Phenotypically normal, but on the basis of pedigree must contain the mutant allele |
Compound Heterozygote | 2 different mutant alleles of the same gene are present (no normal allele) |
What is the transmission pattern for X-linked recessive mutations? | Generally restricted to males (but not all males), rarely seen among females. |
Locus Heterogeneity | Same disease phenotype caused by mutation of different genes |
Name 3 autosomal dominant diseases | Familial Hypercholesteremia (incomplete), Achondroplasia (incomplete), Huntington Disease |
What is incompletely dominant inheritance? | More severe clinical outcome when homozygote vs. heterozygote in autosomal dominant disease. |
Differentiate Consanguinity from Inbreeding: | Inbreeding = isolated population that tends to choose partners from within population. Consanguinity = 2 partners inherit a mutant allele from a single distant common ancestor |
pleiotropy | multiple, often seemingly unrelated, clinical disorders related to a single mutation |
Name 2 X-linked recessive disorders: | Hemophilia A, Androgen Insensitivity Syndrome |
Relative Risk Ratio (RRR) | Prevalence of disease in relatives of an affected person/Prevalence in general population |
Difference in the likelihood of relatives of diseased individuals to report a genetic condition vs. relatives of normal individuals: | Ascertainment Bias |
Greater likelihood to know of other family members experiencing the same condition in diseased vs. control groups (due to knowledge of the disease): | Recall Bias |
Qualitative vs. Quantitative trait: | Quantitative = follows Gaussian distribution in population (e.g. large tonsils), Qualitative = present/absent in disease state (e.g. fibroxanthoma) |
Situations in which monozygotic twins do not have identical genotypes: | 1. somatic rearrangements in T-cell receptor & IgG, 2. X-chromosome inactivation |
Volunteer-Based vs. Population-Based Ascertainment | Volunteer-Based = one twin signs on, then recruits other twin. Population-Based = twins sign up for study and their health is subsequently assessed. |
Heritability (h^2) | 0 if genes contribute nothing to the phenotypic variance. 1 if genes contribute 100%. = (Variance in DZ - Variance in MZ pairs)/(Variance in DZ pairs) |
Multigenic trait disorders | e.g. digenic inheritance in Retinitis Pigmentosa, e.g. Idiopathic Cerebral Vein Thrombosis (2 genetic, 1 environmental factor), 3. Hirschprung Disease, 4. Type 1 Diabetes, 5. Alzheimer's |
Which inheritance pattern shows linear, diagonal, or horizontal inheritance? | Linear = autosomal dominant, Diagonal = X-linked recessive, Horizontal = autosomal recessive |
Sarcoma | Tumor arises in mesenchyme (bone/muscle/connective/nervous system) |
Carcinoma | Tumor originates in epithelial tissue (intestine/bronchi/mammary) |
Gatekeeper Tumor Suppressor Genes | Control cell growth (regulate checkpoint transitions = gates) |
Caretaker Tumor Suppressor Genes | Protect the integrity of the genome (prevent propogation of mutations) |
What is the mechanism of oncogenesis for ABL? | Cytoplasmic Tyrosine Kinase, causing Chronic Myelogenous Leukemia. BCR-ABL protein has constitutive tyrosine kinase activity. (bone marrow leukocyte stem cells) |
What is the mechanism of oncogenesis for CMYC? | Transcription factor causing Burkitt Lymphoma. MYC gene translocates from 8q to 14q -> unregulated gene expression (B-cells) |
What is the mechanism of oncogenesis for BCL2? | Antiapoptotic mitochondrial protein causing Chronic Lymphocytic Leukemia (Bcells). BCL2 translocated from 18q to 14q -> unregulated expression via heavy chain promoter. |
What is the mechanism of oncogenesis for telomerase? | Not a primary oncogenic factor, but likely plays a role in maintenance of the cancerous cell proliferation |
2-hit hypothesis for cancer | genotypic heterozygous for one mutation undergoes second somatic mutation to knock out function of the other allele, OR epigenetic changes shut down other allele |
Loss of heterozygosity (LOH) | When tumor cells contain two identical mutant alleles at an oncogene locus instead of heterozygous alleles. |
Mechanisms for LOH | 1. Interstitial deletion (allele loss), 2. Mitotic recombination (allele loss), 3. Mitotic nondisjunction (chromosome loss), 4. Mitotic nondisjunction + duplication (chromosome loss + new copy of chromosome w/mutant gene) |
What is the difference between genome, chromosome, and gene mutations? | Genome Mutations = change in # chromosomes, Chromosome Mutations = change structure of single chromsome, Gene Mutation = change in individual gene |
What are the consequences of missense mutations? | one codon is replaced with another -> altered protein funtion or altered rate of transcription |
What are the consequences of Chain Termination Mutations? | nonsense mutations (inserted/deleted stop codon) -> unstable mRNA leading to decay or unstable protein leading to degradation. |
What are the consequences of RNA Processing Mutations? | Alternative RNA splicing sites generated |
Mutation Hotspot | Single NT mutations can be transitions (pyrimidine for pyrimidine & purine for purine), or transversions. Hotspots = spontaneous deamination of methylated CpG -> thymidine. Very common mutation. |
mechanism for large deletions/insertions | LINE RNA is reverse transcribed into DNA, and can insert randomly into the genome |
c.365g>a | cDNA mutation in which a guanine was mutated into an adenine at position 365 |
g.IVS365+2T>A | genomic DNA mutation in which the invariant T of the GT 5' splice donor site has been mutated to an A, adjacent to an intervening sequence (used when gene sequence not fully known) |
g.IVS365-1G>C | genomic DNA mutation in which the highly conserved G of the 3' AG splice acceptor site is mutated to C. |
m.365_369delACAC | deletion of 4 nucleotides of mitochondrial DNA beginning at position 365 |
m.365_369insACAC | insertion of 4 nucleotides of mitochondrial DNA beginning at position 365 |
Glu365X | nonsense mutation substituting a stop codon for Glutamate 365 |
dynamic mutation | variable repeat mutations that accumulate over multiple generations of cells/people |
Calculating Mutation Rate | Take # affected individuals from a large n of an autosomal dominant mutation. Mutation rate = # affected/(2 alleles x n) |
Mutation Rate | # new mutations/locus/generation (typically in the range of 10^-4 to 10^-6) |
Genetic Polymorphism | mutation found in >1% of a population |
short tandem repeat polymorphisms (STRP's) | microsatellites = repeats of 2-5 NT's, multiple repeat lengths (alleles) in the population, readily genotyped. 5-25 copies. |
variable number tandem repeats (VNTR's) | minisatellites = repeats of 10-100 NT's. Thousands of copies. |
Copy Number Polymorphism | Repeated segments of DNA, tested by array comparative genome hybridization |
Rh | + have antigen RhD, - lack antigen. (-) mothers w/(+) fetuses make Ab's that attack fetal blood = hemolytic disease. Greater risk for subsequent pregnancies. Treatment = Rh antibodies (RhoGam) to mother to reduce exposure to fetal antigens. |
HLA genes | human leukocyte antigen genes, class I (A, B, C) and II (DP, DQ, DR) encode proteins that present antigens to the lymphocytes. chromosome 6p, part of MHC, order = class II, then III, then I. |
HLA inheritance | clustered on single choromosomal segment 6p (HLA Haplotype), so inherited in entirety from a single chromosome from each parent. Linkage Disequilibrium. |
Ankylosing Spondilitis | autoimmune disease of the spine, caused by HLA B27 polymorphism |
Linkage Disequilibrium | Occurence of specific combinations of alleles @ linked loci more frequently than predicted. Due to low recombination & closely located genes of a common function. |
SNP | 2 alleles only corresponding to 2 different bases @ particular site. Occur 1/1000 base pairs. |
Assumptions in calculating mutation rate: | 1. ascertained cases due to new mutation, 2. full penetration, 3. all new mutations are carried to term, 4. Only 1 mutation can cause the disease |
Stratification | Different subpopulations do not interbreed. Increases frequency of autosomal recessive & dominant disease, only minor effect on X-linked disease. |
Assortative Mating | positive = people choose mates with similar characteristics to themselves (including disease). Increases frequency of autosomal recessive disease. |
Consanguinity and Inbreeding | Consanguinity increases frequency of autosomal recessive disease. |
Linkage Analysis | Compares inheritance of particular stretches of DNA with disease incidence within a family tree |
Association Analysis | Compare frequency of a particular allele between diseased individuals and controls from the same population |
=genes located on the same chromosome | syntenic |
recombination frequency (theta) | between 0 (no recombination)and 1/2 (independent assortment) (proportion, not percentage) |
phase | knowing which alleles are syntenic in the case of an AaBb individual. On same chromosome homologue = in coupling (cis), on different homologues = in repulsion (trans) |
LOD score (logarithm of the odds) | (Z) statistical measure of accuracy per n for recombination events. = [log(10) (likelihood if linked/likelihood if unlinked)]. higher Z = better estimate of theta max. LOD > +3 = odds better than 1000:1 for linkage. |
linkage equilibrium | Equilibrium = frequency of allele within a haplotype is the same as the frequency of the allele within the whole population. |
linkage disequilibrium | Disequilibrium = genes surrounding disease allele inherited at higher than expected rates. |
D' | measure of linkage disequilibrium. 0 = equilibrium, up to 1 = intense disequilibrium. |
Ancestry Informative Markers | SNP's that distinguish different ethnicities |
LD blocks | clusters of SNPs in high linkage disequilibrium |
Disease Odds Ratio | odds of an allele carrier developing a disease = (# diseased allele carriers/# nondiseased carriers)/(# diseased noncarriers/# undiseased noncarriers) |
Relative Risk Ratio | measures strength of an odds ratio: (# diseased carriers/all allele carriers)/(# diseased noncarriers/all noncarriers) |
Limitations of Association Studies | 1. in population stratification, it may be that a particular alleles is associated with a higher risk of disease because multiple alleles are associated with the stratified group (consanguinity), 2. linkage disequilibrium |
tag SNP's | minimum set of SNP alleles necessary for defining a haplotype in a LD block |
What's the best method for mapping short genetic distances? | linkage disequilibrium (D') |
How do you calculate the number of possible haplotypes with complete linkage equilibrium? | 2^n (where n = # SNP's) |
Contiguous Gene Syndrome | poly-phenotypic disorder caused by deletion of contiguous genes along a chromosome. |
balanced translocation meiotic assortment | adjacent 1 (1 of each type of of centromere), adjacent 2 (2 of one type of centromere), alternate = normal/balanced |
pseudohermaphrodite vs. hermaphrodite | pseudohermaphrodite = internal sex organs match karyotype. true hermaphrodite = both testes and ovaries are present. |
Indications for Prenatal Diagnosis by Invasive Testing | 1. Older women, 2. previous child w/ aneuploidy, 3. structural chromosomal abnormality in parent, 4. family history of single-gene disorder, 5. relatives w/neural tube defect, 6. family history of X-linked disorder, 7. + maternal serum/ultrasound screen |
Amniocentesis | 1. invasive, 2. 2nd trimester 15-16 weeks, 3. amniotic fluid contains fetal cells & urine, 4. test AFP, metabolites, chromosomes, enzyme activity, DNA sequencing |
alpha fetoprotein as indicator | immunoassay in maternal serum (MSAFP) or amniotic fluid (AFAFP). high [AFP] indicates anencephaly, spina bifida. (also blood in AF, death, twins, overestimated age |
chorionic villus sampling | 1. invasive biopsy (tertiary villi), 2. 1st trimester (early advantage) 10-12 weeks, 3. cells derived from fetus, 4. test chromosomes, enzyme activity, DNA sequencing (NOTE: too early for AFP, some mosaicism ambiguity) |
MSAFP | catches Down Syndrome (1st trimester) & neural tube defects (2nd trimester) |
1st trimester MSAFP screening | 11-13 weeks, measures PAPP-A (low in Down Syndrome) & hCG (high in Down syndrome but low in trisomy 13 & 18) |
ultrasonography | 2nd trimester & later, look for edema of fetal neck (trisomy marker), other physical abnormalities, growth rate |
2nd trimester MSAFP screening | AFP, hCG, estriol (triple screen). sometimes also inhibin A. All low in all trisomies (except hCG high in Down S) |
types of mosaicism | true = detected in multiple colonies from multiple primary cultures, pseudo = seen only in single cell or derived from single primary culture (usually false positive) |
if unexpected adverse findings from prenatal chromsomes analysis | karyotype the parents (especially for balanced vs. unbalanced structural rearrangements, and for uniparental disomy in region containing imprinted genes) |
Prenatal disease treatment & prevention | termination of pregnancy, metabolic disorder treatment, glucocorticoids for CAH, relief of bladder obstruction, bone marrow transplantation |
preimplantation genetic diagnosis | in vitro fertilization, single blasttomere tested (8-16 cells), DNA analysis for single disorder, only conducted if parents/other child has a disorder |
Genetic screening | public health initiative to identify individuals at increased risk for genetic disease. screen all members of a large population, regardless of family history. |
clinical validity vs. utility | validity = predictive of disease, utility = will cause change to treatment |
sensitivity vs. specificity | sensitivity = fraction individuals w/disease who have the tested-for genotype, specificity = fraction of individuals w/out disease who do not have the tested-for genotype |
positive predictive value | = % chance of developing the disease given a particular genotype, OR % of people with a genotype that actually have the disease |
heterozygote screening | when a high frequency of carriers (e.g. Ashkenazi jews & Tay-Sachs), inexpensive tests, genetic counseling & prenatal diagnosis available, |
gene flow | slow diffusion of genes across large populations |
genetic drift | in small populations, random effects cause a change in allele frequeny |
nondirective counseling | patients provided with information, but are not told what to do regarding testing & managment options |
conditional probabilities | depend on whether the individual in question is a carrier |
What are the odds of 13 successive male births? What are the odds of 13 successive births of a single-sex? | 1. (1/2)^13, 2. 2*(1/2)^13 |
How are genetic vs. allelic diseases treated? | genetic = treat symptoms, identify risk for family. allelic = replace defective protein/minimize consequences, genetic counseling, carrier testing, prenatal diagnosis. increasing protein expression only works when mutant protein is partially functional. |
Diversion Therapy | use of alternative metabolic pathways to reduce concentration of a harmful metabolite. |
Treatment of Enzymopathies | Improve enzyme folding (2-3% improvement, but enough to restore homeostasis). Doesn't work when protein 100% dysfunctional. |
small molecules therapy for skipping over mutant stop codons | nonsense mutation = 11% of defects in human genome. experimental therapy, as yet not fully tested. |
ERT (enzyme replacement therapy) | 1. proteins can be chemically modified (e.g. PEG) to improve pharmacotherapy, 2. intracellular enzymes can be administered extracellularly if substrate is in equilibrium w/extracellular fluid, 3. don't cross BBB, expensive |
best candidates for ERT | CNS not involved, only alternative therapies are high risk, human enzyme available in abundance, biology very well understood |
How are enzymes for Gaucher's Disease targeted to particular cell types & organelles? | modification of the carbohydrates normally decorating the glycoprotein enzyme: terminal sugars are removed & core alpha mannosyl residues target macrophages (then delivered to lysosomes intracellularly) |
What gene expression targeted treatments are appropriate for sickle cell anemia? | DNA hypomethylation increases expression of fetal Hb |
Nuclear Transplantation | = nuclear cloning, transfer of diploid nucleus from adult donor somatic cell into an oocyte cytoplasm |
Therapeutic cloning | uses embryonic stem cells generated by nuclear trnsplantation to form mature differentiated cell types in culture, for transplantation into the donor w/no immune rejection |
reproductive cloning | reimplanting an embryo obtained by nuclear trnsplantation into the uterus of a surrogate mother -> clone of donor human |
What are some examples of genetic disorders treated by hematopoietic stem cell transplantation? | cancer, severe combined immunodeficiency (e.g. beta-thalassemia). Transplanted stem cells release enzymes that are taken up by native cells containing the k/o mutation. Brain perivascular microglia come from marrow. homozygous normal best. |
source of hematopoietic stem cells | bone marrow, placental cord blood (more tolerable for histoincompatibility, widely available, risk of graft-vs.-host disease is reduced) |
what are the essential requirements of gene therapy for an inherited disorder? | 1. known gene identity, 2. cDNA clone, 3. known disease pathophysiology, 4. good risk-to-benefit ratio, 5. low consequences of over/underexpression, 6. target cell w/ long half-life or replicative, 7. successful animal studies, 8. governmental oversight |
ex vivo vs. in vivo gene therapy | ex vivo = gene injected into cells in vitro that are then introduced into the body. in vivo = gene introduced directly into the patient via viruses |
episome | circular viral DNA containing a normal copy of a gene to replace a mutant allele. good for long-lived cells |
Uses for gene therapy | 1. replace mutant gene, 2. inactivate dominant allele, 3. administer pharmacotherapy in vivo |
ex vivo vs. in vivo gene therapy | |
retrovirus DNA transfer | = RNA viruses, incapable of replication, non-cytotoxic, up to 8kb DNA, low copy number inserted. Usually target cell must undergo mitosis, but Lentiviruses (eg. HIV) work in non-dividing cells. |
adeno-associated viruses in DNA transfer | no adverse effects in humans, infect all cells. Inserts only up to 5 b. |
adenoviruses in DNA transfer | easy to produce (high titer), infect all cells, inserts of 30 to 35 kb. Associated w/death due to immune reaction. |
nonviral vectors for DNA transfer | naked DNA, DNA in liposomes, protein-DNA conjugates (where protein binds receptor for transport, etc.), artificial chromosomes. |
limited success of nonviral vectors | DNA tends to be degraded by lysosomes, remaining DNA mostly does not enter the nucleus, inefficient delivery |