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41 Cards in this Set
- Front
- Back
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Mutation |
heritable change in the genetic material |
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Positive/negative sides of mutations |
Positive: evolution Negative: diseases |
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Consequences of mutations |
1. Chromosome mutations - changes in chromosome structure 2. Genome mutations - changes in chromosome number 3. Single-gene mutations - Relatively small changes in DNA structure that occur within a particular gene |
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Mechanism of mutations |
Insertion: adds one or more extra nucleotides into the DNA Deletion: removes one or more nucleotides from the DNA |
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Base substitutions: Transition Transversion |
Transition: replacement of purine base (A,G) with another purine base, or a pyrimidine base (C,T) with another pyrimidine. Transversion: replaceement of a purine with a pyrimidine (Transitions more common than transversions) |
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Point mutations |
Missense mutations: code for different amino acid Nonsense mutations: lead to stop codon - loss of function Silent mutation: code for same aminoacid Frameshift mutation: Insertion or deletion of a single base --> completely different translation from original |
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Sicle cell anaemia |
- missense mutation - autosomal recessesive - mutation in chromosome 11 - homeglobin molecule damaged - heart attack/ stroke |
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Germ-line mutations |
occur directly in a sperm or egg cell, or in one of their precursor cells
passed to future generations The term "mutation" usually refers to germ line mutations in multicellular organisms. |
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Somatic mutations |
occur directly in a body cell, or in one of its precursor cells passed on to other cells through mitosis if it occurs in early development more cells will be affected than in late development. |
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External agent causing DNA damage |
Ionizing radiation: - Ss: will be repaired, leads rarely to mutations - Ds: chromosome rearrangement Ultraviolet irradiation - directl effect on DNA Environmental chemicals - Alkylating agents, chemotherapy agents, aflatoxins, hydrocarbons
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Alkylating agents |
- donate alkyl groups to other molecules - induce transitions, transversions, frameshifts and chromosome aberrations (anomaly) - can change base-pairing properties - can activate repair process error |
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DNA repair/prevention of damage |
Prevention: enzymatic system neutralize potential damaging compounds before they react with DNA - SOD, catalase Repair: easiest way: reverse it directly --> regenerate normal base |
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Excision repair pathways |
(excision=fjerning) - base excision repair - nucleotide excision repair |
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Base excision repair |
- base is damaged - DNA glycosylase removes base - AP endonuclease makes cut - excision exonuclease removes stretch of DNA - polymerase synthesizes new DNA - ligase seals nick |
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Nucleotide excision repair |
- XPA, RPA attach to lesion - TFIIH attaches, unwinnd helix - endonucleolytic cleavage - affected segment removed - resynthesis - gap sealed by DNA ligase |
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post-replication repair |
Homologous recombination: use sister chromatid as template nonhomologous end joining loss of nucleotides --> end joining --> deletion of DNA sequence |
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Defects of DNA repair |
OMIM 278700:XP xeroderma pigmentosum - Individuals with XP are sensitive tosunlight (UV light) - The cells of individuals with XP aredeficient in the repair of UV-induceddamage to DNA. - Individuals with XP may develop skincancer or neurological abnormalities. |
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Xeroderma pigmentosum genes chromosomes function of product |
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Deleterious mutations of coding sequence Coding and regulatory sequences |
reduced frequency due to natural selection show high degree of evolutionary conservation |
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Is mutations pathogenic? |
- Deletions of whole gene, nonsense mutations and frameshift --> destroy gene function - mutations that change conserved nucleotides --> affect splicing --> function - Missense --> pathogenic if protein is functionally important - amino acid substitutions: if noncenservative --> pathogenic |
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Nomenclatures null allele/amorph hypomorph hypermorph neomrph antimorph |
Null allele or amorph: an allele that produces no product. Hypomorph: an allele that produces a reduced amount oractivity of product. Hypermorph: an allele that produces increased amount oractivity of product. Neomorph: an allele with a novel activity or product. Antimorph: an allele whose activity or product antagonizesthe activity of the normal product. |
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A mutation database |
the human gene mutation database |
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Functional effect prediction |
website which allows you to predict the function of a specific mutation |
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Loss of function |
- most often produce recessive phenotypes - haploinsufficiency produces an abnormal phenotype --> dominant heritance |
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gain of function |
usually cause dominant phenotypes common in cancer overexpression may be pathogenic |
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haploinsufficiency |
when diploid organism has only 1 functional copy of a gene - not enough gene product cause diseases! |
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dominant negative effect |
when a mutant polypeptide also interferes with other "healthy" gene products cause more severe effects than deletion and nonsense |
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Mutation analysis |
Goal: - identify all genes that contribute to the process - understand nature of the process Genes identified through their mutant allels |
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Mutation analysis, steps |
- Design an effective mutation-detection system. - Use a mutagen to induce a large collection of mutants thatshow variations in the wild-type process. - Group the mutations into genes. - Map the genes to their chromosomal loci. - Isolate the genes by using DNA technology. - Characterize the structure and function of the genes. - Solve the puzzle of the biological process under study. |
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SNP |
=single nucleotide polymorphism
defined as single base change in DNA that occurs in a significant proportion of a large population
type of point mutation |
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SNP facts |
- found in coding and noncoding regions - occur with high frequency - act as markers for genes close to it - may alter protein structure in coding regions |
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SNP IDs |
each are assigned an "rs number" |
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rs numbers |
- mark a SNP with pharmacological importance - mark a SNP that is susceptible (mottagelig) to polygenic disorders - mark a SNP within a haplogroup - identify a SNP in GWASstudies in sequencing but mutations are preferably marked using regular nomenclature |
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identification of mutations with databases |
www.ensembl.org! |
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The HapMap Project |
- identify and catalog genetic similarities and differences in human beings - researches will be able to find genes that affect healt, disease and individual responses to medications/environmental factors - genetic data from populations with african, asian and european ancestry |
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SNP maps |
- sequence genomes of a large number of people - compare base sequences to discover SNPs - generate single map of human genome containing all possible SNPs |
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SNP profiles |
- genome of each individual contains distinct SNP patttern - people can be grouped based on SNP profile - important for identifying response to drug therapy - correlations btw SNP profiles and specific responses to treatment |
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Haplotype |
(Google def: set of genetic determinants located on a single chromosome) 1. may be one locus, several loci, or entire chromosome - depending on number of recombination events in given set of loci 2. OR a set of SNPs on single chromatid that are statistically associated 3. OR series of alleles found at linked loci on single chromosome |
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Genetic drift |
(Google def: random changes in the frequency of alleles in a gene pool, usually of small populations) |
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3 specific situations of genetic drift |
1. Continuous drift: number of population is low 2. Bottleneck effect: when number of the population will be reduced significantly over short period of time. 3. Founder effect: if new population is created by small number of individuals |
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Negative consequence of drift: |
- fixation of previously polymorphic loci - decreased genetic diversity due to allelic loss - increased ratio of homozygous individuals - accumulation of disadvantegous mutants and rare alleles - strengthening of differentiation between populations |
