Clinical Genetics Flashcards
(159 cards)
1
Q
Germ Line
A
Sex cells
2
Q
Deamination
A
The removal of an amino group
3
Q
Depurination
A
Loss of bases from a DNA double helix
4
Q
Cytotoxic
A
Toxicity to living cells
5
Q
Progenitor
A
An ancestor
6
Q
Endogenous
A
Growing or originating from within an organism
7
Q
Exogenous
A
Growing or originating from outside an organism
8
Q
Nucleotide Excision Repair
A
The repair of bulky, helix-distorting DNA lesions. A section of about 30 nucleotides is removed and resynthesis of DNA is performed based on the template strand.
9
Q
Base Excision Repair
A
The repair of lesions of a single base, either that had been deleted or modified. DNA glycosylase cleaves the sugar-base bond, removing the base. The correct nucleotide is added.
10
Q
Endonucleases
A
An enzyme that cute DNA or RNA at an internal position in the chain.
11
Q
Nonhomologous End Joining
A
Form of repair of double strand breaks in DNA that involves the fusion of broken ends without copying from a DNA template.
12
Q
Microhomology-mediated End Joining
A
An error-prone alternative double-strand break–repair pathway that uses sequence microhomology to recombine broken DNA. Although MMEJ has been implicated in cancer development, the mechanism of this pathway is unknown.
13
Q
Microhomology
A
The presence of the same short sequence of bases in different genes.
14
Q
Homologous Recombination
A
A type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may be also RNA in viruses). It is widely used by cells to accurately repair harmful breaks that occur on both strands of DNA, known as double-strand breaks (DSB).
15
Q
Senescence
A
The process of deterioration with age.
16
Q
Homologs
A
A couple of homologous chromosomes.
17
Q
Homologous
A
Having the same structure.
18
Q
Compound Heterozygote
A
The presence of two different mutant alleles at a particular gene locus, one on each chromosome of a pair.
19
Q
Haplotype
A
A group of alleles in an organism that are inherited together from a single parent.
20
Q
Pleiotropy
A
When one gene influences two or more seemingly unrelated phenotypic traits.
21
Q
Expressitivity
A
The degree to which a phenotype is expressed by individuals having a particular genotype.
22
Q
Consanguity
A
The fact of being descended from the same ancestor.
23
Q
Terotogens
A
Something that can cause birth defects or abnormalities in a developing embryo or fetus upon exposure. Teratogens include some medications, recreational drugs, tobacco products, chemicals, alcohol, certain infections, and in some cases, health problems such as uncontrolled diabetes in pregnant people.
24
Q
Amniocentesis
A
A procedure performed during pregnancy to obtain amniotic fluid to test for chromosomal abnormalities and fetal infections.
25
Chronic Villus Sampling
A type of prenatal diagnostic test to detect chromosomal problems that can result in genetic diseases and birth defects. It involves taking a small sample of part of the placenta (the chorionic villi) where it is attached to the wall of the uterus.
26
Cytogenic Analysis
The analysis of blood or bone marrow cells that reveals the organization of chromosomes.
27
CFTR
Cystic fibrosis transmembrane conductance regulator is a membrane protein and chloride channel in vertebrates that is encoded by the CFTR gene. The CFTR gene codes for an ABC transporter-class ion channel protein that conducts chloride ions across epithelial cell membranes. Mutations of the CFTR gene affecting chloride ion channel function lead to dysregulation of epithelial fluid transport in the lung, pancreas and other organs, resulting in cystic fibrosis.
28
Myocardial Infraction
Damage to the heart muscle caused by a loss of blood supply due to blocks in the arteries. Heart attack.
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Imprinting
An epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the mother or the father.
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Mitochondrial Heteroplasmy
The presence of more than one type of mitochondrial DNA within a cell or individual.
31
Modifier Genes
Genes that affect the phenotypic and/or molecular expression of other genes.
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Dynamic Mutations
An unstable heritable element where the probability of expression of a mutant phenotype is a function of the number of copies of the mutation.
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Pathogenic Mutations
A change in the genetic sequence that causes a specific genetic disease.
34
Huntington's Disease
A condition that leads to progressive degeneration of nerve cells in the brain that affects movement, cognitive functions, and emotions.
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Myotonic Dystrophy
A disease that affects the muscles and other body systems. It is the most common form of muscular dystrophy that begins in adulthood, usually in a person’s 20s or 30s. This disease is characterized by progressive muscle loss and weakness.
36
Fragile X Syndrome
A genetic condition inherited from parents which results in various developmental problems like intellectual disabilities and cognitive impairment.
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Red Blood Cells
A type of blood cell that is made in the bone marrow and found in the blood. Red blood cells contain a protein called hemoglobin, which carries oxygen from the lungs to all parts of the body.
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Epigenetic
Heritable, but not produced by a change in the DNA sequence.
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Heterochromatin
Chromatin that remains highly condensed throughout the cell cycle and is generally genetically inactive.
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Interphase
G1, S, and G2 phases.
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Monozygotic
Originating from a single zygote, as in identical twins.
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Transcription Unit
A segment of DNA, the transcribed region, that is used to make a primary RNA transcript. May occasionally span multiple genes.
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Splice Donor Site
The site that defines the junction between the end of an exon in RNA and the start of the following intron.
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Splice Acceptor Site
The site that defines the junction between the end of an intron in RNA and the start of the following exon.
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Open Reading Frame
A continuous sequence of coding DNA.
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Untranslated Region
Regions at the 5' end of mRNA before the AUG translation start codon, or at the 3' end after the stop codon.
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Antisense RNA
A RNA transcript that has a complementary sequence to a mRNA, or some functional noncoding RNA. Naturally occurring antisense RNAs, made using the non-template strand of a gene, are important regulators of gene expression.
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Transposon
A mobile genetic element.
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Psuedogenes
A DNA sequence that shows a high degree of sequence homology to a non-allelic functional gene but is itself nonfunctional or does not make a protein like its closely related homolog, but it may make a nonfunctional non-coding RNA.
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Euchromatin
The fraction of the nuclear genome that contains transcriptionally active DNA and that, unlike heterochromatin, adopts a relatively extended conformation.
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Ortholog
Homologous genes present in different organisms having descended from a common ancestral gene.
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Purifying
Negative selection. A form of natural selection in which harmful mutations that wreck or disturb the function of an important DNA sequence tend to be removed from the population.
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Segmental Duplication
The existence of very highly related DNA sequence blocks on different chromosomes, or at more than one location within a chromosome.
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Retrogene
A functional gene that appears to be derived from a reverse-transcribed RNA.
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Retroposon
A member of a family of mobile DNA elements that transpose by making a RNA that is copied into a cDNA which integrates elsewhere in the genome.
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Constitutional Variation
Genetic variation that we inherit and that is present in our cells.
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Somatic Genetic Variation
DNA changes occur in the DNA of our cells throughout life.
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Antigen
A molecule that can induce an adaptive immune response or that can bind to an antibody or T-cell receptor.
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Replication Slippage
A mistake in replication of a short tandemly repeated DNA sequence that results in newly synthesized DNA strand with more or fewer copies of the tandem repeats than in the template DNA.
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Cross-linking
Abnormal occurance of covalent bonds directly linking two bases. The cross-linked bases may be on the same strand or opposite strands.
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DNA Strand Breakage
A single strand may be broken by simple cleavage of a phosphodiester bond or by a more complex single strand break, in which one of more of the ends have been damaged and sometimes one or more nucleotides have been deleted. Double strand breaks are when both strands have been broken in the same place or within close proximity.
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Base Deletion
Hydrolysis cleaves the covalent N-glycosidic bond connecting a base to a sugar.
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Base Modification
Altered bonding or added chemical groups.
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Intrastrand Cross-linking
Linking of two bases on the same strand.
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Interstrand Cross-linking
Linking of two bases on complementary strands.
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Hydrolysis
Any chemical reaction in which a molecule of water breaks one or more chemical bonds.
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Reactive Oxygen Species
ROS. Chemically reactive molecules or atoms containing oxygen, such as oxygen ions, oxygen radicals, and peroxides. Formed within cells as a natural by-product of normal oxygen metabolism, they have important roles in cell signaling and homeostasis but cause DNA damage.
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Mutagens
An agent that results in an increased mutation frequency.
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Abasic Site
Result from a single base deletion.
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Long-patch Repair
Base excision repair, but for replacing multiple bases.
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Single-strand Break Repair
Breaks detected and repaired by ligase.
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Homologous Recombination (HR)-mediated DNA Repair
Uses a template strand to perform the repair, after replication, and before mitosis.
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Progeria
Symptoms that mimic accelerated aging: premature grey hair, cataracts, osteoporosis, type II diabetes, atherosclerosis, and death before the age of 50. Seen in Werner syndrome.
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Translesion Synthesis
A DNA damage tolerance process that allows the DNA replication machinery to replicate past DNA lesions such as thymine dimers or AP sites. In short, the process involves specialized polymerases either bypassing or repairing lesions at locations of stalled DNA replication.
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Indel
Insertion or deletion.
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CNV
Copy Number Variation. A change in copy number of sequences that result in larger deletions and insertions, usually more than 100 nucleotides up to megabases.
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Satellite DNA
20kb to many hundreds of kilobases, located at centromeres, and some other heterochromatic regions.
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Minisatellite DNA
100bp to 20kb, found primarily at telomeres and subtelomeric locations.
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Microsatellite DNA
Fewer than 100bp long, widely distributed in euchromatin. Used in genetic mapping.
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Nascent
Newly synthesized.
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Structural Variation
Large-scale DNA variation that involves moving or changing the copy number of moderately long to very long DNA sequences, by one of various mechanisms; translocations, inversion, insertion, deletion, or duplication.
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Purifying (negative) Selection
A form of natural selection in which harmful mutations that wreck or disturb the function of an important DNA sequence tend to be removed from the population.
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Positive Selection
Individuals who possess the advantageous DNA variant may have increased survival and reproductive success rates. The DNA variant then increases in frequency and spreads throughout a population.
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Selective Sweep
Process whereby positive selection for a favorable DNA variant causes a reduction in variation in the population at the immediately neighboring nucleotide sequences.
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Balancing Selection
Selection working simultaneously in opposite directions on the same variant; can result in heterozygotes for a harmful mutation having a higher biological fitness than normal homozygotes.
86
Heterozygote Advantage
The situation where a person heterozygous for a mutation has a reproductive advantage over both homozygotes for this mutation and also normal homozygotes. Sometimes called overdominance, heterozygote advantage is one reason why severe recessive diseases may remain common.
87
T-cell Receptors
Displayed on the surface of T cells, they work in cell-mediated immunity, along with proteins encoded by the major histocompatibility complex (MHC).
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Class I MHC Proteins
They are expressed on the surface of almost all nucleated cells and enable cytotoxic T lymphocytes to recognize and kill host cells that are infected by a virus or other intracellular pathogen.
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Class II MHC Proteins
They are displayed on the surface of very few types of cells, notably immune system cells that present foreign antigen to be recognized by helper T lymphocytes.
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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.
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Junctional Diversity
The somatic recombination mechanisms that bring together different gene segments in Ig or T-cell receptor genes variably add or subtract nucleotides at the junctions of the selected gene segments.
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Protein Chain Combinatorial Diversity
Igs and T-cell receptors are heterodimers, and diversity is compounded by unique combinations of two unique protein chains.
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Allelic Exclusion
A process by which only one allele of a gene is expressed while the other allele is silenced.
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Somatic Hypermutation
This mechanism only applies to Igs and is used to further increase variability in the variable region after somatic recombinations have produced functional VDJ or VJ units.
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Cytotoxic T Cells
A T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.
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Endoplasmic Reticulum
A network of membranous tubules within the cytoplasm of a eukaryotic cell, continuous with the nuclear membrane. It usually has ribosomes attached and is involved in protein and lipid synthesis.
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Cytoplasm
All of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus.
98
Dendritic Cells
Antigen-presenting cells (also known as accessory cells) of the immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems.
99
Macrophages
A large phagocytic cell found in stationary form in the tissues or as a mobile white blood cell, especially at sites of infection.
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B Cells
A type of white blood cell that makes antibodies. B lymphocytes are part of the immune system and develop from stem cells in the bone marrow.
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Endogenous
Growing or originating from within
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MHC Restriction
The ability of T cells to recognize antigens when associated with the organism’s own MHC haplotype, providing a dual recognition system critical to T-cell function.
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Epigenetics
Heritable, from mother cell to daughter cell, or sometimes from parent to child, but not produced by a change in the DNA sequence.
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Hemizygous
Having only one copy of a gene or DNA sequence in diploid cells. Males are hemizygous for most genes on the sex chromosomes. Deletions occurring on one autosome produce hemizygosity in males and in females.
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Mendelian
Description for a character whose pattern of inheritance suggests it is caused by variation at a single chromosomal locus.
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Monogenic
Involving or controlled by a single gene.
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Co-dominant
Phenotypes that result from mutations at a single gene locus can be simultaneously displayed by the heterozygote.
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Sib
Sibling
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Sibship
A series of brother and sisters.
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Consaguineous
Couples who have one or more recent ancestors in common.
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Compound Heterozygote
A child that has two different mutant alleles.
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The Coefficient of Relationship
The proportion of alleles shared by two persons as a result of common genetic descent from one or more recent common ancestor.
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The Coefficient of Inbreeding
The probability that a homozygote has identical alleles at a locus as a result of common genetic descent from a recent ancestor.
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Barr Body
X chromosome that has been inactivated is induced to form a highly condensed chromosome that is mostly transcriptionally inactive.
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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.
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Heteroplasmy
Mosaicism, usually within a single cell, for mitochondrial DNA variants.
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Segregation Ration
The overall proportions of affected children within multiple families with the same disorder.
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Ascertainment Bias
When data for a study or an analysis are collected (or surveyed, screened, or recorded) such that some members of the target population are less likely to be included in the final results than others.
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Gameotogenesis
The process in which cells undergo meiosis to form gametes.
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Genetic Mosaicism
Genetically distinct populations of cells that have different mutational spectra.
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Germ-line Mosaicism
An individual who has a subset of germ-line cells carrying a mutation that is not found in other germ-line cells.
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Pleiotrophic Disorder
Many different body systems and functions are impaired.
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Cilia
An organelle found on eukaryotic cells in the shape of a slender protuberance that projects from the much larger cell body.
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Penetrance
The probability that a person who has a mutant allele will express the disease phenotype.
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Non-penetrance
The disease can appear to skip a generation in a person who must have inherited the disease allele is unaffected.
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Imprinting
An epigenetic phenomenon in which the expression of the gene is determined by its parental origin.
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Dynamic Mutations
Those mutations caused by the expansion of existing polymorphic DNA repeat sequences beyond a copy number threshold. These genetic mutations can give rise to dominant, recessive or X-linked disorders, dependent upon the location of the repeat sequence with respect to the genes that are affected by the expansion.
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Anticipation
The tendency for the severity of a condition to increase in successive generations. Commonly due to bias of ascertainment, but a genuine outcome in the case of some dynamic mutations.
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Selfish Mutation
Disease-associated mutations that occur spontaneously in the sperm of most men and their levels typically increase with age.
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Revertant Mutations
Denotes any mutational process or mutation that restores the wild-type phenotype to cells already carrying a phenotype-altering forward mutation. Forward mutations confer a gene sequence and phenotype different from that conferred by the wild-type gene.
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Balancing Selection
Selection working simultaneously in opposite directions on the same variant; can result in heterozygotes for a harmful mutation having a higher biological fitness than normal homozygotes.
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Heterozygote Advantage
The situation when a person heterozygous for a mutation has a reproductive advantage over both homozygotes for these mutations and also normal homozygote, sometimes called overdominance. Heterozygote advantage is one reason why severe recessive disease may remain common.
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RNA Interference
Post-Transcriptional Gene Silencing (PTGS). A conserved biological response to double-stranded RNA that mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids and regulates the expression of protein-coding genes.
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Enhancer
A DNA sequence that increases the level of transcription of a gene that is located nearby on the same chromosome.
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Gene Dosage
The number of copies of a particular gene present in a genome. Gene dosage is known to be related to the amount of gene product the cell is able to express; however, the amount of gene product produced in a cell is more commonly dependent on regulation of gene expression. Nonetheless, changes in gene dosage (copy number variations) due to gene insertions or deletions can have significant phenotypic consequences.
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Spliceosome
A large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specific proteins to form a small nuclear ribonucleoprotein complex (snRNP, pronounced “snurps”), which in turn combines with other snRNPs to form a large ribonucleoprotein complex called a spliceosome. The spliceosome removes introns from a transcribed pre-mRNA, a type of primary transcript. This process is generally referred to as splicing.
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Splice Donor Site
Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICESOMES. They are joined during the RNA SPLICING reaction, forming the junctions between exons.
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Heterodisomy
A type of uniparental disomy in which two different homologous chromosomes and their frequently different alleles are inherited from the same parent.
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Splice Acceptor Site
Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICESOMES.
140
Isodisomy
A form of uniparental disomy in which both copies of a chromosome, or parts of it, are inherited from the same parent. It differs from heterodisomy in that instead of a complete pair of homologous chromosomes, the fertilized ovum contains two identical copies of a single parental chromosome. This may result in the expression of recessive traits in the offspring. Some authors use the term uniparental disomy and isodisomy interchangeably.
141
Branch Site
In RNA splicing, the site to which the 5'-guanylate at the end of an intron is joined to an adenylate residue within the intron through a 2',5'-phosphodiester bond to form a 'lariat' intermediate.
142
Uniparental Disomy
Occurs when a person receives two copies of a chromosome, or of part of a chromosome, from one parent and no copy from the other parent. UPD can be the result of heterodisomy, in which a pair of non-identical chromosomes are inherited from one parent or isodisomy, in which a single chromosome from one parent is duplicated. Uniparental disomy may have clinical relevance for several reasons.
143
Genomic Imprinting
An epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the mother or the father. Genes can also be partially imprinted. Partial imprinting occurs when alleles from both parents are differently expressed rather than complete expression and complete suppression of one parent's allele. Forms of genomic imprinting have been demonstrated in fungi, plants and animals.
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Nonsynonymous Substitution
A nucleotide mutation that alters the amino acid sequence of a protein.
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Missense Substitution
A point mutation in which a single nucleotide change results in a codon that codes for a different amino acid.
146
Conservative Substituition
An amino acid replacement in a protein that changes a given amino acid to a different amino acid with similar biochemical properties.
147
Dominant-negative Effect
A circumstance in which a mutation occurs that results in a gene product adversely affecting wild-type gene products—all in the same cell.
148
Non-allelic Homologous Recombination
A form of homologous recombination that occurs between two lengths of DNA that have high sequence similarity but are not alleles.
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Dynamic Mutation
An unstable heritable element where the probability of expression of a mutant phenotype is a function of the number of copies of the mutation. That is, the replication product (progeny) of a dynamic mutation has a different likelihood of mutation than its predecessor. These mutations, typically short sequences repeated many times, give rise to numerous known diseases, including the trinucleotide repeat disorders.
150
Fragile Site
A specific heritable point on a chromosome that tends to form a gap or constriction and may tend to break when the cell is exposed to partial replication stress. Based on their frequency, fragile sites are classified as "common" or "rare". To date, more than 120 fragile sites have been identified in the human genome.
151
Contiguous Gene Syndrome
Also known as a contiguous gene deletion syndrome. A clinical phenotype caused by a chromosomal abnormality, such as a deletion or duplication that removes several genes lying in close proximity to one another on the chromosome.
152
Gene Conversion
The process by which one DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion event. Gene conversion can be either allelic, meaning that one allele of the same gene replaces another allele, or ectopic, meaning that one paralogous DNA sequence converts another.
153
Inverted Repeat
A single stranded sequence of nucleotides followed downstream by its reverse complement.
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Microdeletion
A chromosomal change in which a small piece of a chromosome is deleted in each cell.
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Microduplication
A chromosomal change in which a small amount of genetic material on a chromosome is abnormally copied (duplicated).
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Derivative Chromosome
A structurally rearranged chromosome generated either by a chromosome rearrangement involving two or more chromosomes or by multiple chromosome aberrations within a single chromosome (e.g. an inversion and a deletion of the same chromosome, or deletions in both arms of a single chromosome). The term always refers to the chromosome that has an intact centromere.
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Acentric
Lacking a centromere.
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Polyploidy
A condition in which a diploid cell or organism acquires additional sets of chromosomes.
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Null Allele
A nonfunctional allele (a variant of a gene) caused by a genetic mutation. Such mutations can cause a complete lack of production of the associated gene product or a product that does not function properly; in either case, the allele may be considered nonfunctional.
