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| Enhansosome attracts the enzyme _______ changes shape of the histone, moves out of the way of the promoter and transcription begins | acetylase |
| _______ groups also added or taken from histones that shuts the DNA off, turns transcripton off | methyl |
| What is RNA interferencce? | A natural process that destroys specific mRNA molecules "shuts off" using small interfering RNA that result from transcribing short sequences on both DNA strands. |
| When does RNA interference occur? | After transcription, it occurs when complimentary DNA strands are transmitted and a hairpin loop froms, certain proteins trim the hairpin creating a small interfering RNA known as siRNA |
| How much of the human genome actually codes for proteins? | 1.5% of the human genome encodes protein |
| What are some of the explanations for the difference between the number of genes and the number of proteins present in humans? | Some genes could specify more than one protein by mixing and matching exons through alternate splicing. |
| Alternate Splicing | Multiple proteins from a single gene, it explains how a long sequence of DNA can specify more mRNA than genes. It enables a cell to manufacture different versions of a protein by adding or deleting parts. |
| In alternate splicing, introns are _______ amd exons are ________. | removed, retained. |
| What kinds of DNA sequences make up the non-coding DNA found in the human genome? | Viral DNA, Non-coding RNAs (dont make proteins, 1/3 of human genome transcribed), Introns, Promoters, other controls, repeats (transposons "jumping genes", telomeres, centromeres, pseudogenes, others) |
| What is a mutagen? | o A change in a DNA sequence that is present in less than 1% of individuals in a population. If present in < 1% - polymorphism (benign, beneficial) May occur at the molecular or chromosomal level. The effect of mutations vary (generally bad = mistakes). |
| “Loss of function” | reduces/stops the gene, recessive |
| “Gain of function” | more alleles, too much of a gene, dominant. |
| Somatic mutations | mutations occur in any cell of the body except the germline which only occur in gametes. All the cells that descend from the original changed cell are altered but they might only compress a small part of the body. Affect subsequent somatic cell decendants. Not transmitted to offspring. |
| Germline mutations | mutations occur in the germline cells and have the possibility of transmission to offspring. |
| Sickle Cell anemia | Mutation encodes valine in place of glutamic acid. Phenotype associated with homozygones. Altered surface of hemoglobin allows molecules to link in low oxygen conditions (creates sickle cell shape of RBC). Sickling causes anemia, joint pain, and organ damage when RBC become lodged in small blood vessels. |
| Balanced polymorphism of Sickle Cell anemia | Malaria less susceptible |
| Thalessemia | Caused by another beta hemoglobin mutation. Too few beta hemoglobin molecules. Excess of alpha hemoglobin leads to iron release, which destroys RBC, damages heart, liver, and endocrine glands. |
| Thalassemia minor | heterozygous (benign, mild) |
| Thelassemia major | homozygous for mutation and more severe (more symptomatic) |
| • What are the two basic classes of mutations? | o Spontaneous and Induced mutations |
| • What causes spontaneous mutations? | o Errors in DNA replication. Not caused by exposure to known mutagen. DNA bases have slight chemical instability. Exist in altering forms called tautomers. As replication fork encounters unstable tautomers mispairing can occur. (Grabs the wrong base because slightly unstable) |
| • What causes induced mutations? | Caused by mutagens (external to the organism), many are also carcinogens and cause cancer. Examples: Alkylating agents: remove a base (chem), Acridine dyes: add or remove a base (chem.), X-Rays: break down chromosomes and delete a few neucleotides (radiation), UV radiation: creates thymidine dimmers (acts on DNA where thymine is present and changes the helix by linking thymines together changes replication changes protein synthesis transcription. (radiation) |
| Point mutations | A change of a single nucleotide |
| Point mutations: transition | replaces purine: A to G or G to A |
| Point mutations: transversion | purine replaces pyrimidine or pyrimidine replaces purine: A,G to T, C or T,C to A,G (swap different bases) |
| Missense mutations | A point mutation that changes the codon. Caused by a substitution of an amino acid. They can affect protein function severely, mildly, or not at all. (change one nucleotide, alters one code, alters amino acid, which changes meaning |
| Example of missense mutations | Hemoglobin mutation, Glautamic acid to valine causes sickle cell anemia. |
| Nonsense mutations | A point mutation changing a codon for an amino acid into a stop codon. It creates truncated proteins that are often nonfunctional. Some have dominant effects due to interference with normal functions. (will make short protein – not translated to correct length – process never finishes) |
| Example of nonsense mutations | A factor XI deficiency is a nonsense mutation changing glaucomic acid to a "stop" (process never finishes), short protein cannot function in clotting |
| Splice site mutations | Alters a site where introns are normally removed. Intron translated or exon skipped (mistake in mutation, got rid of entire chuck of splice |
| Examples of splice site mutations | CF mutation, BRCA1, Familial dysautonomia (FD) |
| Insertions and deletions | The genetic code is read in triplet nucleotides. Addition or subtraction of nucleotides not in multiples of three leads to a change in the reading frame (transcriped and translated in 3’s). Causes a frameshift and alters amino acids after mutation. (By inserting or deleting) The addition or subtraction of nucleotides in multiples of three leads to addition or subtraction of entire amino acids. |
| Expanding repeats | Insertion of triplet repeats leads to extra amino acids. Some genes are particularly prone to expansion of repeats (more= bad). # of repeats correlates with earlier onset and more severe phenotype. |
| What is Anticipation (Expanding repeats) | the expansion of the triplet repeat with an increase in severity of phenotype with subsequent generations (gets worse in generations, adding more and more repeats). |
| o What are the types of excision repair and how do they work? | Damaged DNA is removed by excision of the bases. Bases are replaced by a DNA polymerase. Nucleotide excision repair: replaces up to 30 bases, used in repair of UVB and some carcinogens (responsible and larger chucks of DNA) Base excision repair: replaces 1-5 bases, repair oxidative damage (smaller scale enzymes) |
| o What does mismatch repair do? | Enzymes detect nucleotides that do not base pair in newly replicated DNA. The incorrect base is excised and replaced. Proofreading is the detection of mismatches. |
| Expanding repeats example | Hunntington Disease-specific gene makes a protein called hunntingtin NKfunction, gene normally suppost to have 10-34 copies of CAG (glutamine) when it gets larger it becomes toxic, polyglutamine disease (add triplets) |
| Repair Disorders: Trichothiodystrophy | Five genes, Symptioms reflect accumulating oxidative damage (short stature, mental retardation, premature aging). Faulty nucleotide excision repair or base excision repair or both |
| Repair disorders: Xeroderma Pigmentosa (XP) | autosomal recessive, mutation in any 7 genes, malfunction of excision repair or deficient "sloppy" DNA polymerase, allow thymine dimers (UV-B biproducts) to remain and block replication, must avoid UV light, rare-only 250 cases worldwide |
| Centromere | o Is the largest constriction of the chromosome and where spindle fibers attach |
| Telomeres | o Are chromosomes tips composed of many repeats of TTAGGG and shorten with each cell division (built in timer for how long that chromosome lives) o Ends of DNA molecule, that prevents tips from joining together. |
| Subtelomeres | o The chromosome region between the centromere and telomeres. Near telomere the repeats similar to the telomere sequence |
| • Heterochromatin vs. euchromatin | o Heterochromatin = darkly staining, contains mostly repetitive DNA (non-coding) & o Euchromatin = contains more protein encoding genes |
| The p arm vs. the q arm of a chromosome | p arm = short, q arm = long |
| What is a karyotype? | A size-order chromosome chart |
| • How are human chromosomes numbered? | 46 chromosomes , 23 diploid chromosomes Paired homologs of chromosomes 1 to 22 Sex chromosomes (XX or XY) |
| • What are the different arrangements of centromeres found in chromosomes? | Different in different chromosomes, but same in the same chromosomes, Telocentric = at the tip, Acrocentric = close to end, Submetacentric = displaced from center , Metacentric = at midpoint |
| • How do polyploidy and aneuploidy differ? | o Polyploidy is a cell with extra set of chromosomes. Triploid is 3 copies of each chromosome and o Aneuploidy is a cell with an extra or missing chromosome. |
| What is nondisjunction? | A meiotic error that causes aneuploidy |
| What if nondisjunction happens in Meiosis I? | Nondisjunction during meiosis I results in copies of both homologs in one gamete. Two monosomes, two trisomes. |
| What if nondisjunction happens in Meiosis II? | Nondisjunction during meiosis II results in both sister chromatids in one gamete. Two normal zygotes, one monosome, one trisome |
| • What are the two most common forms of aneuploidy? | o Monosomy = one chromosome absent and Trisomy = one chromosome extra |
| Trisomy 13 (patau syndrome) | very rare and generally do not survive 6 months, medical and physical abnormalities, facial malformation and eye fusion |
| Trisomy 21 (down syndrome) | distinctive facial and physical problems, many medical problems are treatable, varying degree of developmental disabilities |
| Trisomy 18 (Edward symdrome) | most due to nonjunction in meiosis II in oocyte and do not survive, serious medical and physical disabilities |
| o Why are there so few trisomies? | Others tend to be lethal |
| Turner Syndrome (45,X) | only one copy of X chromosomes, absence of Y leads to development as a female, phenotype includes short stature, webbing at back of neck, incomplete sexual development (infertile), hearing impairment mosaics only when some of the cells are effected, but females run the risk of passing the disorder on through gametes |
| Triplo-X Aneuploidy (47,XXX) | 1 in 1,000 female births. Extra copy of every X-linked gene. Few modest effects on phenotype include tallness, menstrual irregularities, and slight impact on intelligence. X-inactivation of two X chromosomes occurs and cells have 2 Barr bodies. May compensate for presence of extra X |
| Klinefelter Syndrome (47,XXY) | 1 in 1,000 male births. Extra copy of each X-linked gene feminized. Phenotypes include; incomplete sexual development, rudimentary testes and prostate, long limbs, large hands and feet, some breast tissue development. Some cases are not diagnosed until fertility problems arise or remain undiagnosed |
| XXYY Syndrome | Likely arises to unusual oocyte and sperm. AAD, obsessive compulsive disorder, learning disabilities, infertile. Treated with testosterone |
| XYY Syndrome (47, XYY) | 1 in 1,000 male births. Extra Y chromosome. 96% phenotypically normal. Modest phenotypes may include; great height, acne and minor speech, reading disabilities. Studies suggesting increase in aggressive behaviors are not supported |
| Deletions | Missing copies of genes (the chromosome breaks and the piece never gets fixed and it floats away) |
| Duplications | Extra copies of genes (occurs when unequal crossing) **larger regions of deletion or duplication increase the likelihood that there will be an associated phenotype |
| Translocations | Nonhomologous chromosomes exchange segments |
| Robertsonian translocation: | • Two nonhomologous acrocentric chromosomes break at the centromere and long arms fuse. The short arms are often lost. 5% of Down syndrome results from a Robertsonian translocation between chr 21 and chr 14. |
| Reciprocal translocation | • Two nonhomologous chromosomes exchange a portion of their chromosome arms. Some individuals carry a translocation but are not missing any genetic material unless a translocation breakpoint interrupts a gene |
| Inversions | Inverted chromosomes have a region flipped in orientation. 5-10% cause health problems probably due to disruption of genes at the breakpoints. Inversions may impact meiotic segregation (one normal, 3 abnormal) |
| Two types of inversions occur: | Paracentric - inverted region does NOT include centromere. Pericentric - inverted region includes centromere |
| What are isochromosomes? | Chromosomes with identical arms. Form when centromeres divide along the incorrect plane during meiosis |
| What are ring chromosomes? | o Chromosomes shaped like a ring. Occur in 1 in 25,000 conceptions. May arise when telomeres are lost and sticky chromosome end fuse. Ring chromosomes have phenotypes associated with the loss or addition of genetic material |
| What is uniparental disomy? | o Happened when you get 2 copies from one parent. Problem during imprinting because certain genes are shut off and don’t receive functional copies because both “shut off” Maternal = both from mom Paternal = both from dad |
| Two sets of each chromosome is a | Diploid |
| One set of each chromosome is a | Hapliod (gametes) |
