Gene Interaction - Genetics - Notes | BIOL 3166, Study notes of Genetics

Download Gene Interaction - Genetics - Notes | BIOL 3166 and more Study notes Genetics in PDF only on Docsity! Chapter 6 Gene Interaction Haplosufficient gene – half of w.t gene is sufficient for w.t phenotype; Mutations are recessive HaploINsufficient gene – half of w.t gene is NOT sufficient and gives a mutant phenotype; Mutations are dominant; requires 100% of HI gene for w.t phenotype. Dominant Negative – Refers to the negative effect of a mutant allele. NOTE: Mutations are dominant/recessive Genes are haplosufficient/haploINsufficient Incomplete Dominance – Allele is not dominant or recessive, instead it is an intermediate in which the heterozygote is a mixture of the parent phenotypes. (ex. White x Red = Pink) Codominance – Both alleles of a heterozygote contribute to the phenotype. (ex. A/B = AB phenotype) Autotrophic Mutants – A mutant that can’t grow in the minimal medium w/o being supplied w/ additional nutrients that are not required by the w.t. Epistasis (double mutant) – when ≥ 2 mutations are in the same pathway; the phenotype of a double mutant shows phenotype of one mutation and not the other. Genetic complementation (double mutant) – the production of w.t phenotype when double heterozygous mutations are on different genes in a diploid. Genetic complementation by suppression (double mutant) – The production of a phenotype close to w.t by the addition of a mutation in another gene; often involves multi-subunit protein complexes. Non-complementation 1. 2 mutations in the same gene 2. Epistasis – linear pathway disrupted 3. Epistasis – One gene regulates the function/expression of the other. 4. Intergenic non-complementation – when 2 genes are haplosufficient, but their fxn t/g is required at 100%. (ex. ½ A x ½ B = haploINsufficient) but ( A /B = haplosufficient) Chapter 7 DNA : STRUCTURE AND REPLICATION Structure of DNA:  A-T and C-G base pair; Hydrogen bonded  Deoxyribose sugar o 1’ nitrogenous base o 2’ H o 3’ OH o 5’ Phosphate group  The two strands of the double helix are anti-parallel and complementary to each other Replication of DNA o DNA Polymerase o adds new nt to the 3’ OH end o acts at the replication fork, where double helix is unwound by helicase. o Can’t initiate replication, can only extend existing chain. o Synthesis occurs 5’---->3’ o Leading strand – continuous in direction of replication fork. (3’ facing fork) o Lagging strand – discontinuous opposite the replication fork. o Synthesis on lagging strand 1. Primase synthesizes short RNA oligonucleotides (primers) 2. DNA polymerase III elongates RNA primers with new DNA 3. DNA polymerase I removes RNA primer at 5’ end and fills gaps 4. DNA ligase seals gaps Replisome - a molecular machine made up of many proteins and nucleic acids during DNA replication. (i.e Helicase, topoisomerase, DNA poly I, DNA poly II, Primase, DNA, and ssBP.) DNA replication proceeds in two direction from the origin of replication. “Proofreading” activity of DNA polymerases: they can excise incorrect nts by 5’-3’ exonuclease activity; absent in RNA so there are more errors. Prokaryote Replication o Initiation o Occurs at oriC site only during certain times in the life of a cell. Eukaryote Replication o Initiation Functional RNAs o snRNA- mechanism of exon splicing o siRNA – (small interfering RNA)short dsRNA produced by the cleavage of long dsRNA by DICER. o Result in gene and transgene silencing and viral resistance o dsRNA- (double stranded RNA) o composed of a sense coding strand and a complementary antisense strand o trigger mechanism that results in the destruction of complementary mRNA. o RNase – non specific enzyme that degrades all mRNAs Mechanism of RNAi 1. DICER chops up dsRNA into siRNA 2. RISC binds to siRNA and unwinds them into single stranded siRNA to destroy the bound antisense complementary mRNAs. 3. Results in repressing gene expression Transgene – a gene that has been introduced into the chromosome in the lab; a way to generate dsRNA in a cell. Cosupression – occurs when both the transgene and the endogenous gene fail to produce a protein product resulting in gene inactivation. (ex. Purple petunia). Chapter 11 Regulation of Gene Expression in Eukaryotes Bacterial transcriptional Regulation: o Ground state is usually always on and the gene is always expressed because there is no gene regulation, so genes need to be repressed. Eukaryotic transcriptional Regulation: o Ground state is usually off and the gene needs to be activated for gene to be expressed. Promoter-proximal elements – located upstream of the promoter of a eukaryotic gene; required for efficient transcription of the gene. Transcriptional activator proteins o Gal4 - a DNA binding protein that binds to UAS and promotes transcription in the presence of galactose o Is a dimer composed of an activation domain and DNA-binding domain which are both necessary for transcription. o Recruits Transcriptional Machinery - Binding to UAS recruits TBP + TFIID and RNA poly II + Mediator to initiate txn. o Induced by Galactose and Gal3 which restrict Gal80 from binding to Gal4 Histone post-translational modification o HDAC – histone deacetylase; removes acetyl groups and forms heterochromatin (gene silencing/turn off gene transcription). Turns off gene transcription in the presence of glucose, with or w/o galactose. o Mig1 prevents activation of Gal genes. Also, recruits Tup1 which contains HDAC. o Mig1 is a DNA binding repressor that binds in the presence of glucose o Deacetylation causes the loss of SWI/SNF binding o HAT – histone acetyl-transferase; adds acetyl groups and forms euchromatin (gene expressed) o SWI/SNF- facilitates nucleosome remodeling to expose TATA sequences for txn activation via TBP binding………… Enhancesoome – help recruit transcriptional machinery and chromatin remodelers. (ex. β- interferon gene) o Lg. protein complex made of regulatory proteins to activate txn 1. Forms binding site for GCN5 contains a HAT adds ac-groups to Nucleosome 2. CBP coactivator binds to recruit RNA poly II and SWI/SNF binds to expose TATA 3. TBP binds to TATA to initiate txn. o B-inerferon gene is turned off in humans; turned on by viral infection Enhancer-blocking insulator – when positioned b/t and enhancer and a promoter, it prevents the enhancer from activating txn at the promoter by moving promoter into a loop and closing it off. Genomic Imprinting o Maternal imprinting – Igf2 allele is expressed in a mouse only if it is inherited from the mouse’s father; the gene derived from the mother is inactive. o ICR (imprinting control region) is unmethylated in female gametes and binds CTCF, forming an insulator that blocks enhancer activation of Igf2. o Paternal imprinting – H19 allele is expressed in a mouse only if inherited from mom; gene derived from dad is inactive. o Methylation of the ICR in male germ cells prevents CTCF binding o Imprinting – imprinted genes are expressed as if there were only one copy of the gene present in the cell even through there are two. o Requires insulators