Clinical Genetics 2 Flashcards
Promoters
A combination of short sequence elements, usually just upstream of a gene, to which RNA polymerase binds so as to initiate transcription of the gene.
Transcription Factor
DNA-binding protein that promotes the transcription of genes. Some are ubiquitous, promoting transcription in all cells, but many are tissue-specific.
Exon Skipping
An occasional failure when one or more full-length exons are not represented in some transcripts.
Isoforms
Alternative form of a protein produced from individual genes as a result of a differential expression or through the production of different but highly related proteins from two or more loci.
siRNA
Short Interfering RNA. Double-stranded RNA molecule 21-22 nucleotides long that can dramatically shut down the expression of genes through RNA interference.
Gene Silencing
Gross reduction in gene expression that occurs naturally by altering epigenetic settings, and that can occur both naturally and artificially through RNA interference.
Epigenetic Marks
Epigenetic settings. Patterns of epigenetic modification, notably DNA methylation, histone modifications, and nucleosome spacing.
Chromatin Remodeling
Movement, dissociation, or reconstitution of nucleosomes in chromatin, as part of the systems controlling chromatin conformation.
CpG Island
Short stretch of DNA, often less than 1kb long, containing frequent unmethylated CpG dinucleotides. CpG islands tend to mark the 5’ regions of genes.
Epimutation
An abnormal epigenetic change. A change in chromatin organization that causes a change in expression of one or more genes without any change to the DNA sequence.
Synonymous Substituition
Silent substitution. A mutation that does not change the amino acid sequence, but sometimes causes altered splicing and disease.
Nonsynonymous Substitution
A mutation that causes a change in the amino acid sequence.
Missense Mutation
A mutation that causes a change in the amino acid sequence.
Conservative Substitution
A nucleotide substitution that changes the amino acid sequence by one of the same chemical class and often has minimal consequences.
Nonsense Mutation
A nucleotide substitution that replaces an amino acid with a stop codon.
Cryptic Splice Site
A sequence in pre-mRNA with significant homology to a splice site. May be used as splice sites when splicing is disturbed or after a base substitution mutation that increases the resemblance to a normal splice site.
Nonsense-mediated Decay
NMD. A mRNA surveillance mechanism that degrades most mRNA transcripts that have a premature stop codon, more than 50 nucleotides upstream from the last splice junction.
Unequal Crossover
UEC.
Dynamic Mutations
An unstable dynamic repeat that changes in size between parent and child.
Fragile Sites
Located on a chromosome where the chromatin of metaphase chromosomes can appear condensed under certain culture conditions.
Premutation Allele
Among diseases caused by dynamic mutations, a repeat expansion that is large enough to be unstable on transmission but not large enough to cause disease.
Unequal Crossover
UEC. One chromatid with an insertion and one with a deletion.
Unequal Sister Chromatid Exchange
UESCE. An exchange between sister chromatids where one chromatid with an insertion and one with a deletion.
Direct Repeats
Two or more copies of a sequence that occur in the same 5’ to 3’ direction on a single DNA strand. Usually used to mean repeats that are separated on the DNA; repeats that are directly adjacent to one another are normally described as tandem repeats.
Constitutional Mutation
Present in the genetic material of the zygote, and therefore present in every nucleated cell of a person.
Mosaic
An individual who has two or more genetically different cell lines derived from a single zygote. The difference may be point mutations, large-scale mutations, or chromosomal abnormalities.
Derivative Chromosome
A chromosome that has been structurally rearranged.
Isochromosome
An abnormal symmetrical chromosome consisting of two identical arms.
Nondisjunction
Chromosomes fail to separate during Anaphase I.
Chimera
An organism derived from more than one zygote.
Anaphase Lag
Can result in aneuploidy, when a chromosome or chromatid is delayed in its movement during anaphase and lags behind the others.
Null Allele
Any mutant allele where the normal gene product is not made or is completely non-functional.
Dosage-sensitive
A chromosomal gene that, when present in one copy instead of the normal two copies (causing reduced expression), is associated with disease. Disease can also sometimes result from an increased number of copies (with consistent overexpression).
Haploinsufficiency
A locus shows haploinsufficiency if producing a normal phenotype requires more gene product than the amount produced by a single functional allele.
Dominant-negative Effect
The situation in which a mutant protein interferes with the function of its normal counterpart in a heterozygous person.
Homoplasmy
Of a cell or organism, having all copies of the mitochondrial DNA identical, as opposed to heteroplasmy.
Heteroplasmy
Mosaicism, usually within a single cell, for mitochondrial DNA variants.
Modifier Genes
A gene whose expression can influence a phenotype resulting from a mutation at another locus.
Haplotype
A series of alleles at two or more neighboring loci on a single chromosomal DNA molecule.
Recombinants
In linkage analysis, a gamete that contains a haplotype with a combination of alleles that is different from the combination that the parent had inherited.
Lod Score
A measure of the likelihood of genetic linkage between loci. The log base (base 10) of the odds that the loci are linked (with recombination fraction q) rather than unlinked. For Mendelian characters a lod score greater than +3 provides minimal evidence of linkage; one that is less than -2 is evidence against linkage.
Autozygosity
In an inbred person, homozygosity for alleles identical by descent.
Quantitative Trail Loci
QTL. A locus that contributes to determining phenotype of a continuous character.
Susceptibility Factor
A variant that provides increased risk of developing a specific disease.
Phenocopies
A person or organism that has a phenotype normally caused by a certain genotype but does not have that genotype. Phenocopies may be the result of a different genetic variant, or of an environmental factor.
Heritability
The proportion of the causation of a character that is due to genetic causes.
Risk Ratio
The disease risk to a relative of an affected person divide by the disease risk to an unrelated person.
Innate Immune System
System of nonspecific response to a pathogen using the natural defense of the body, as opposed to the adaptive immune system.
Association
A tendency of two characters (such as diseases or marker alleles) to occur together at nonrandom frequencies. A simple statistical observation, not a genetic phenomenon, but can be caused by linkage disequilibrium.
Case-control Studies
A study in which samples from affected individuals (cases) are analyzed and compared with equivalent samples from unaffected control individuals.
Odds Ratio
In case-control studies, the relative odds of a person with or without a factor under study being a case.
Stratification
A population is stratified if it consists of several subpopulations that do not interbreed freely. Stratification is a source of error in association studies and risk elimination.
Linkage Disequilibrium
A structural association between particular alleles at separate but linked loci, normally the result of a particular ancestral haplotype being common in the population studied. An important tool for high-resolution mapping.
Haplotype Blocks
A region of DNA showing limited haplotype diversity.
Sensitivity
The proportion of all true positives that the test is able to detect.
Specificity
A measure of the performance of a test that assesses the proportion of all people who do not have the condition who are correctly identified as such by the test assay.
Epistasis
Literally ‘standing above’. Gene A is epistatic to gene B if A functions upstream of B in a common pathway. Loss of function of A will cause all the effects of loss of function of B, and maybe other affects as well.
Epigenome
The totality of epigenetic marks in a cell.
Adaptive Immune System
Specific immune responses that rely on recognition of foreign antigen by antibodies and T-cell receptors.
Augmentation Therapy
Therapy that is provided to the patient that supplements a severely depleted, or missing factor, thereby overcoming the deficiency and restoring function, as opposed to the great majority of drug therapies that are designed to inhibit some disease process.
Pharmacogenetics
The study of the roles of specific genes on metabolism or function of drugs.
Pharmacokinetics
The study of what the body does with, and to, the drug (drug absorption, activation, metabolism, and excretion).
Pharmacodynamics
The study of how the person is affected by the drug.
Prodrug
An inactive precursor to a therapeutic drug that is administered to a patient and activated within the body after natural conversion by a drug-metabolizing enzyme or other component.
Intrabodies
Intracellular antibodies.
Stem Cells
A cell that can act as a precursor to differentiated cells but retains the capacity for self-renewal.
Transduction
Use of viruses to transfer DNA into human cells.
Embryonic Stem (ES) Cell Lines
The first pluripotent stem cells to be developed. Immortal and can give rise to all cells.
Reprogramming
Large-scale epigenetic changes to convert the pattern of gene expression in a cell to that typical of another cell type or cell state. Often occurs in cancer.
Transdifferentiation
Epigenetic reprogramming of the nucleus of a cell, causing it to change from one cell type to another, such as from skin to a neuron.
Dedifferentiation
Epigenetic reprogramming of a differentiated cell so that the cell becomes less specialized.
Transit Amplifying Cell (TAC)
The immediate progeny by which stem cells give rise to differentiated cells.
Blastocyst
An embryo at a very early stage of development when it consists of a hollow call of cells with a fluid-filled internal compartment.
Inner Cell Mass (ICM)
A group of cells located internally within the blastocyst which will give rise to the embryo proper.
Induced Pluripotent Stem (IPS) Cells
Somatic cells that have been treated with specific genes, gene products, or other agents to reprogram them to resemble pluripotent stem cells.
Episome
Any DNA sequence that can exist in an autonomous (self-replicating) extrachromosomal form in the cell.
Tropism
The specificity of a virus for a particular cell type, determined in part by the interaction of viral surface structures with receptors present on the surface of the cell.
Retroviruses
Single-stranded RNA viruses with a reverse transcriptase function, that can be converted into complementary DNA.
Transgenic Animal
An animal in which artificially introduced foreign DNA becomes stably incorporated into the germ line.
Gene Targeting
Artificial genetic modificationon of a specific predetermined gene in intact cells, such as embryonic stem cells.
Gene Knockout
The targeted inactivation of a predetermined gene within intact cells so as to artificially create a null allele.
Gene Silencing
Gross reduction in gene expression that occurs naturally by althering epigenetic settings, and that can occur both naturally and artificially through RNA Interference.
Gene Knockdown
Targeted inhibition of expression of a specific gene by various methods, for example using siRNA.
Genome Editing
Artificial manipulation of an intact cell that is designed to make a double-strand break at just one locus and subsequently to make a desired change to the base sequence at that locus.
Zinc Finger Nucleases
Synthetic enzymes that combine an endonuclease module with a sequence-specific targeting module, so as to cleave DNA at a selected sequence.
Zinc Finger Nucleases
Synthetic enzymes that combine an endonuclease module with a sequence-specific targeting module, so as to cleave DNA at a selected sequence.
Drug Efficacy
A drug’s capacity to produce an effect (such as lowering blood pressure).
Poor Drug Metabolizer
Medication is broken down very slowly. May experience side effects at standard doses.
Intermediate Drug Metabolizer
Slow rate of metabolism. May have too much medication at standard doses, potentially causing side effects.
Ultrafast Drug Metabolizer
Medication is rapidly broken down. Medication may be removed from a patient’s system too quickly to provide symptom relief.
Hybridoma
A method for producing large numbers of identical antibodies. This process starts by injecting a mouse with an antigen that provokes an immune response. A type of white blood cell, the B cell, produces antibodies that bind to the injected antigen. These antibody producing B-cells are then harvested from the mouse and, in turn, fused with immortal B cell cancer cells, a myeloma, to produce a hybrid cell line called a hybridoma, which has both the antibody-producing ability of the B-cell and the longevity and reproductivity of the myeloma.
Effector Molecules
A small molecule that selectively binds to a protein and regulates its biological activity. Can also directly regulate the activity of some mRNA molecules (riboswitches).
Gene Therapy
A technique that modifies a person’s genes to treat or cure disease.
Germ-line Gene Therapy
Performing modifications on embryos in an attempt to forestall incurable diseases which arise from abnormal mitochondria.
Somatic Cell Gene Therapy
The introduction of novel genetic material into somatic cells to express therapeutic gene products. This emerging technology holds great promise for the treatment of both inherited and acquired diseases.
Somatic Cell Gene Therapy
The introduction of novel genetic material into somatic cells to express therapeutic gene products. This emerging technology holds great promise for the treatment of both inherited and acquired diseases.
Zinc Finger Proteins
Amongst the most frequently occurring proteins.
TALENS
Restriction enzymes that can be engineered to cut specific sequences of DNA. They are made by fusing a TAL effector DNA-binding domain to a DNA cleavage domain (a nuclease which cuts DNA strands). Transcription activator-like effectors (TALEs) can be engineered to bind to practically any desired DNA sequence, so when combined with a nuclease, DNA can be cut at specific locations. The restriction enzymes can be introduced into cells, for use in gene editing or for genome editing in situ, a technique known as genome editing with engineered nucleases. Alongside zinc finger nucleases and CRISPR/Cas9, TALEN is a prominent tool in the field of genome editing.
Regenerative Medicine
The “process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function”. This field holds the promise of engineering damaged tissues and organs by stimulating the body’s own repair mechanisms to functionally heal previously irreparable tissues or organs.
Transgene
A gene which is artificially introduced into the genome of another organism.
Transfection
The process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: “transformation” is typically used to describe non-viral DNA transfer in bacteria and non-animal eukaryotic cells, including plant cells.
Transfection
The process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: “transformation” is typically used to describe non-viral DNA transfer in bacteria and non-animal eukaryotic cells, including plant cells.
In Vivo
In a living organism.
In Vitro
In a test tube, culture dish, or elsewhere outside a living organism.
In Vitro
In a test tube, culture dish, or elsewhere outside a living organism.
Recombinant DNA
DNA that has been formed artificially by combining constituents from different organisms.
Integrating Viral Vector
Lentivirus and gammaretrovirus vectors. Fuse a fragment of their genetic material into the host cell genome. These vectors are often characterized by stable and long-term expression of the transgene.
Graft Vs Host Disease
A common complication of an allogeneic stem cell transplant. It happens when the T-cells of the new immune system, recognize the recipient’s cells as foreign, and attack them. This causes a war between the ‘graft’ and the ‘host’.
Non-Homologous End Joining
A pathway that repairs double-strand breaks in DNA. NHEJ is referred to as “non-homologous” because the break ends are directly ligated without the need for a homologous template, in contrast to homology directed repair, which requires a homologous sequence to guide repair.
Homology Directed Repair
A mechanism in cells to repair double-strand DNA lesions. The most common form of HDR is homologous recombination. The HDR mechanism can only be used by the cell when there is a homologous piece of DNA present in the nucleus, mostly in G2 and S phase of the cell cycle.
