MM 6-10 Flashcards

Question

Aneuploidy

Answer 1

Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. Most cases of aneuploidy result in miscarriage.

Answer 2

A translocation is a chromosome abnormality caused by rearrangement of parts between NONhomologous chromosomes. Translocations can be balanced (an even exchange of material with no genetic information extra or missing, and ideally full functionality) or unbalanced (where the exchange of chromosome material is unequal resulting in extra or missing genes). Several forms of cancer are caused by translocations.

Answer 3

Copy number variation (CNVs) is when large sections of the genome (>1000 base pairs) are repeated. The number of repeats in the genome varies between individuals causing necessary population variation. We all have CNVs, which can amplify certain gene expression. Pathogenic consequences result in autism, epilepsy, Huntington's disease. It is thought to occur during crossing over in meiotic recombination.

Answer 4

An SNP is a variation in a single nucleotide that occurs at a specific position in the genome, including sense, missense, non-sense point mutations. Does not include insertions and deletions. We all carry about 3.5 million SNPs. Most are benign. Some are not; sickle cell anemia and cystic fibrosis.

Answer 5

A microsatellite is a tract of repetitive DNA in which certain DNA motifs (2–5 base pairs) are repeated, typically 5–50 times. Microsatellites occur at thousands of locations within the genome, although most are in introns. They rarely cause disease. Used for paternity tests and in forensic identification.

Answer 6

Aneuploidy in which an extra chromosome is present due to nondisjunction. Can occur in meiosis 1 or 2. Eg trisomy of ch21 leads to down syndrome.

Answer 7

Trisomy of chromosome 13. 80% die within first year. Mental and muscular development issues. Polydactyly, microchephaly, and many other side effects.

Answer 8

Trisomy of chromosome 18. Babies born small with heart defects. 50% die in first week.

Answer 9

Monosomy of the X chromosome. Typically infertile, do not develop breast or menstruate, have a thick webbed neck, develop heart issues and have a shorter life expectancy.

Answer 10

A point mutation is a type of single nucleotide polymorphism that causes a single nucleotide base substitution, insertion, or deletion of the genetic material, DNA or RNA. Includes synonymous (silent), and nonsynonymous [nonsense (premature stop codon), and missense (different codon)]. Considered small-scale pathogenic mutations.

Answer 11

A genetic mutation that does not alter the phenotype of an organism. When within the exon of a gene, silent mutations are generally synonymous mutations, coding for the same amino acid

Answer 12

A point mutation that codes for the same amino acid due to the degeneracy of the genetic code. Synonymous mutations are silent point mutations.

Answer 13

A nonsense mutation is a non-synonymous point mutation in which a codon is prematurely made into a stop codon. This causes the protein to be shortened because of the stop codon interrupting its normal code. How much of the protein is lost determines whether or not the protein is still functional.

Answer 14

A missense mutation is a non-synonymous point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. Depending on the location, missence mutations can be conservative (properties of protein remain the same) or nonconservative (protein function changes). E.g sickle cell anemia.

Answer 15

A point mutation that alters the amino acid sequence of a protein. It is contrasted with synonymous substitution which do not alter amino acid sequences. Includes missense and nonsense mutations.

Answer 16

A point mutation in which an amino acids is inserted or deleted.

Answer 17

Includes point mutations and aberrant splicing. Compared to large-scale pathogenic mutations.

Answer 18

Mutation caused by the skipping or introduction of an exon during splicing.

Answer 19

Includes aneuploidy, translocations, and copy number variation. Compared to small-scale mutations.

Answer 20

Considered a characterization of cancer. One genetic mutation causes a cellular change, which in turn causes more mutations within the cell, sometimes allowing for rapid growth, the bypassing of safety mechanisms, rapid division, resistance to apoptosis and then metastasis.

Answer 21

A driver mutation increases genomic instability and can lead to cancer. Driver mutations often increase the occurrence of other mutations. Eg, a mutation that bypasses safety mechanisms or speeds cell growth/division.

Answer 22

2 lineages that can occur from chromosomal aberration.

Answer 23

When two acrocentric chromosomes merge together, rather than swapping. There is one fewer chromosome but not necessarily lost DNA. 50% chance that offspring is viable, and another 50% that it has down syndrome (if 14-21 translocation).

Answer 24

History of miscarriages Chromosomal abnormality Age of mother Abnormal ultrasound

Answer 25

dysmorphic features developmental delay Clinical signs specific to chromosomal disorder. Infertility, many miscarriages Family history of heritable chromosomal abnormality.

Answer 26

Genomic imprinting is the phenomenon by which certain genes are expressed in a parent-of-origin-specific manner (randomly determined). If the allele inherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed. The process involves DNA methylation and histone methylation without altering the genetic sequence. A small proportion (<1%) of genes are imprinted, meaning that gene expression occurs from only one allele. Human diseases involving genomic imprinting include Angelman syndrome and Prader–Willi syndrome.

Answer 27

the gold standard for future testing. Same resolution as FISH, but genome wide detection. Should be applied to all cases of developmental daly, intellectual disability, autism or congenital anomalies.

Answer 28

Used to detest chromosomal abnormalities and other large scale genetic disorders.

Answer 29

Used for insertions or deletion disorders when cause is suspected.

Answer 30

DNA-binding domain-the sequence specific binding domain. Trans-activating domain (TAD) contains binding sites for other proteins such as transcription coregulators. Optional signal sensing domain (SSD) is a ligand binding domain), which senses external signals and, in response, transmits these signals to the rest of the transcription complex,

Answer 31

The 3’ outermost segment is cleaved by an endonuclease. The Poly A polymerase adds adenosine 40-250 residues. Slows degradation by exonucleases in cytosol. The longer the tail, the longer the lifespan of RNA.

Answer 32

Different exons of a gene may be included or excluded from the final, processed messenger RNA (mRNA) produced from that gene. Consequently, the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions. Regulation is done with splicing activators that promote the usage of a particular splice site, and splicing repressors that reduce the usage of a particular site.

Answer 33

The addition of 7 methylguanosine residue, to which proteins bind, protecting RNA from nuclease attack. It also allows for nuclear export of RNA; the caps are recognized by the nuclear pore complex for export into the cytoplasm.

Answer 34

micro RNA are small noncoding strands of RNA that regulate expression. They are complementary to a particular mRNA and will bind to it, downregulating expression by preventing translation.

Answer 35

rRNA; Ribosomal RNA, accounts for 80-90% of RNA in cells. It is produced by transcription but not translated. It plays a structural and enzymatic role in ribosomes.

Answer 36

tRNA; Transfer RNA, transcribed but not translated. Covalently bind Amino acids and transports them to ribosome.

Answer 37

mRNA; Messenger RNA, translated and contains instructions for protein synthesis. RNA polymerase: Several types make different types of RNA. Do not require primer. Reads 3-5 and builds from 5-3.

Answer 38

Editing events may include the insertion, deletion, and base substitution of nucleotides within the edited RNA molecule. Whan codons are introduced at various places protein structure changes, generating protein diversity.

Answer 39

Differential splicing RNA editing Multiple promoters and multiple polyadenylation sites.

Answer 40

Activators are transcription factors that enhance the interaction between RNA polymerase and a particular promoter, encouraging the expression of the gene. They can recruit chromatin modifiers to loosen DNA (which will neutralize lysine tails on histamine). Enhancers are sites on the DNA helix that are bound by activators.

Answer 41

Transcription factors can also prevent transcription and removal will initiate transcription. Silencers are regions of DNA sequences that, when bound by particular transcription factors, can silence expression of the gene.

Answer 42

A protein that binds to DNA and regulates gene expression by promoting or suppressing transcription.

Answer 43

Controlling the rate of gene transcription for example by helping or hindering RNA polymerase binding to DNA

Answer 44

upregulation, activation, or promotion –

Answer 45

downregulation, repression, or suppression

Answer 46

A protein that works with transcription factors to increase the rate of gene transcription.

Answer 47

A protein that works with transcription factors to decrease the rate of gene transcription.

Answer 48

A specific sequence of DNA that a transcription factor binds to.

Answer 49

A specific sequence of DNA that a transcription factor binds to.

Answer 50

``` Ligand binding De/Phosphorylation Expression-levels and location Cofactors Proteolytic cleavage ```

Answer 51

Rapid protein turnover ensures that protein levels are appropriate as needs change.

Answer 52

Degrades proteins that are imported into the cell

Answer 53

Degrades cytosolic proteins marked for destruction

Answer 54

Membrane organelles within the cell that degrade proteins, nucleic acids, carbs and lipids. They arise from the endoplasmic reticulum. They have proton pumps that produce a low pH within (pH 4). They also have acid hydolases. They receive contents by fusing with membranes from autophagosomes, phag/pino/endocytosis.

Answer 55

An autophagosome is a spherical structure with double layer membranes. After formation in the ER, autophagosomes deliver cytoplasmic components to the lysosomes. The outer membrane of an autophagosome fuses with a lysosome to form an autolysosome. The lysosome's hydrolases degrade the autophagosome-delivered contents and its inner membrane.[

Answer 56

Proteins and organelles are packed into autophasomes, which then fuse with lysosomes for degradation.

Answer 57

LSDs are a group of metabolic disorders that result from defects in lysosome or autophagasome function, which require many critical enzymes. If one of these enzymes is defective the large molecules accumulate within the cell, eventually killing it.

Answer 58

The process by which proteins are marked and targeted for destruction by proteosomes. Ubiquitin chains are added to lysine residues to mark destruction

Answer 59

Small proteins that are added in chains to lysine residues. Poly-ubiwuitin chains are biomarkers for proteosomal degradation.

Answer 60

Proteasomes are large, barrel shaped protein complexes located in the nucleus and the cytoplasm. They are composed of at least 7 alpha and 7 beta subunits. They degrade unneeded or damaged proteins by proteolysis and are part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. Targeted proteins enter the complex and are proteolyzed by proteases (trypsin, chymotrypsin). The degradation process yields peptides of about seven to eight amino acids long, which can then be further degraded into shorter amino acid sequences and used in synthesizing new proteins. Proteins are tagged for degradation by ubiquitin chains, which bind to the proteasome, allowing it to degrade the tagged protein.

Answer 61

A ubiquitin ligase (E3) assists in the transfer of ubiquitin to the lysine reside of a protein substrate. There are hundreds of different E3s, providing substrate specificity. Mutations can cause disease.

Answer 62

Ubiquitin is activated by ubiquitin activating enzyme (E1) Ubiquitin is then conjugated by ubiquitin conjugating enzyme (E2). Ubiquitin is transferred to the target protein by ubiquitin ligase (E3), which recognizes the target substrate

Answer 63

Parkin is a protein that is a component of a multiprotein E3 ubiquitin ligase complex, thereby assisting in protein degradation. Mutations in this gene cause Parkinson's disease.

Answer 64

MDM2 is a protein involved in an E3 ubiquitin ligase that targets p53 (which is a tumor suppressor). Upregulation of MDM2 is seen in many cancers.

Answer 65

- Ligand bonding - Cleavage (zymogens -> enzyme) - Phosphorylation - Ubiquitination - Fatty acid modification - Glycosylation

Answer 66

- Activates - Deavtivates - Conformational change - Promotes interactions

Answer 67

Allows protein to attach to membranes and other proteins.

Answer 68

Phosphorylase adds phosphate (kinase). Phosphatase removes phosphate (dephosphorylation by hydrolyses)

Answer 69

Prader–Willi syndrome is a genetic disorder due to loss of function of specific genes on chromosome 15. Symptoms include weak muscles, poor feeding, and slow development, often accompanied by obesity and type 2 diabetes. Occurs due to a deletion on the father's chromosome 15. Due to imprinting, the maternally inherited copies of these genes are virtually silent, and only the paternal copies of the genes are expressed. Deletion on the same gene but on the mother's side results in Angelman syndrome (AS).

Answer 70

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe intellectual and developmental disability, sleep disturbance, seizures, jerky movements (especially hand-flapping), frequent laughter or smiling, and usually a happy demeanor. AS is a classic example of genomic imprinting in that it is caused by deletion or inactivation of genes on the maternally inherited chromosome 15 while the paternal copy, which may be of normal sequence, is imprinted and therefore silenced.

Answer 71

TATA box is a DNA sequence found in the promoter region of some genes. It is the binding site of either general transcription factors or histones (the binding of a transcription factor blocks the binding of a histone and vice versa) and is involved in the process of transcription by RNA polymerase. During the process of transcription, the TATA binding protein (TBP) normally binds to the TATA-box sequence, which unwinds the DNA and bends it through 80°. The AT-rich sequence of the TATA-box facilitates easy unwinding, due to weaker base-pairing interactions between A and T bases, as compared to between G and C. The TATA box is usually found at the binding site of RNA polymerase II.