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Probability # favorable outcomes · Plevent) = total # of outcomes independentvs dependent outcomes Sum rule=2 mutually exc...

Probability # favorable outcomes · Plevent) = total # of outcomes independentvs dependent outcomes Sum rule=2 mutually exclusive outcomes ↓ either/ or · Product rule-2 independent outcomes ↳ both · order not specified = multiply by outcomes Binomial theorem flips) ! -outcomes ex · , (H) ! X (HT) ! · subtraction principle : 1- PCOw) Mendel's Law + Meiosis · Mendels experiments monohybrid result in 3 : 1 ratio -2 cross always - result in 9 : 3 : 31 ratio f2 dihybrid cross always - ↓ because independent assortment of gametes - Meiosis equal segregation heterozygote makes 2 gamete types in = proportion · = independent assort. -dihybrid generates + gamete types in proportion Human Pedigrees human traits controlled by single genes (Mendelian traits) are usually diseased Dominance pattern = appears in every generation · Recessive pattern : T in every generation affected people ↳ unaffected parents can have affected progeny require conditional probability · 1. You need to use all info abt an individual ↓ 23 if you know they Not are affected. you want to consider multiple 2 possibilities Dominance Normal alleles (wild-type) - normally functional protein · Abnormal allelesw no protein , nonfunctional , partially funct. oddly funct. Abnormal allele be dominant to normal when · can 1. Abnormal is nonfunctional+ gene dosage matters wine. Abnormal allele 2 has unusual function Dominance explained in 3 ways 1. Dominant allele is normal that makes normal protein 2. Dominant allele is abnormal ; makes nothing 3. Dominant allele is abnormal ; makes abnormal protein Incomplete dominance in between phenotype · 31 - :2 : 1 F2 codominance = both phenotypes show on monohybrid · Blood type - It + /B = codominant I 13- i , completely dominant to -0 : universal donor -AB = universal receiver Pleiotropy one gene controls more than one trait · - & lead to non-mendelian 2 : 1 in 82 may progeny ratios , on monohybrid Gene Interactions Complex traitw controlled by dominance a gene interactions ↓ continuous= Quantitative eye color , height ex : , etc , ↳ Discontinous Discrete ex : white heart disease : , purple or , Interactions btw pairs of genes Additive interactions : 9 : 3 : 3 : 1 ratio I retained when in dihybrid control - can be genes the same trait thru indep pathways , ex : colorless Entan B Epistatic graa two genes work colorless ty in : > - same pathway , 9 : 3 : 3 : 1 is altered · Recessive epistasis : ee epistatic to B and blo ↑ covers allele  complimentation can occur w/ epistasis ↓ gamete of each parent provides functional allele that other parent lacks Penetrance fraction of individuals that · = display Phenotype Sex Chromosomes gene on the / chromosome determines maleness ↳ SRY sex reversed if if added gene , lacking or · X-linked inheritance females inherit dad X male inherit all X-linked gene from mom -males humzygous of all X-linked genes Dosage compensation XX XX cells produce same amount X-linked gem product · : + Barr bodies inactivation - = X-chromosome Inkage unlinked (independent assortment) in Mendels genes are · alleles of tend to be inherited genes close ty ty : linked linkage alters 9 :3 : 3 : 1 dihybrid ratio linkage about crossing over durring meiosis linked fewer recombinant · = , no 9:3:3 :/ ↳ 750 % P , 150% R unlinked = 50% P , So % D R Recombination frequency · : R linkage group = all genes on a chromosome Mutation change BP sequence of DNA · in point mutations · 1.Substitution Forward : Normal - Mutant (nonfunctional) 2 Deletion. Reverse : Mutant Normal 3 Insertion. most mutations in human come from males · Bacteria : Ames Test auxotrophs mutants that cannot complete biosynthesis pathway - : ↓ needs supplement doesn't prototrophs need supplement to - : grow - reverse mutation : auxotroph o prototroph ; His - Hist How can prototrophs (Hist) be detected in a culture of auxotrophs (His] ? measure rate of his hist - Y - his auxotrophs in his"culture can be detected w/ screen - - his " can be detected in his culture using seletion SELECTION used - Drosphilia : Muller's Test · - SCREENED for forward mutations detect X-ray-induced lethal mutations - -Fl females mated w/ wild-type to see how many produce sons W/ paternal X chromosome as X-ray & more progeny had bar-eye - , How Mutations Used to Define Gene complimentation test-reveal · which mutations alleles of same are gene - (t) = normal progeny a complementation () = mutant complimentation - o no progeny diff BP within crossing btw · over single gene will generate wild type supplimentation test Deciphering the Genetic Code code is colinear we a non-overlapping sequence · ad · missense = substitutions mutation , diff amino acid result  Amino acid % 31 ↑ S Interpreting Genetic Code 5 tRNAs = adapters btw codons + amino acids ↳ tRNA-transcript of gene anticodon -Euros' a nonsense mutation truncates protein 3. codon (mRNA) at C termini = end nonsense supressor mutation - mutation in gene for tRNA that allows tRNA to bind to stop codon to allow normal length · wobble = flexability at 3rd BP · degenerate = > I codon : 1 amino acid · wobloe : one tRNA can decode : 1 codon Genetic Structure + Classification Allele ATG Poly-A Exont Exon 2 Exon3 I signal DNA Intron Intron 2 I promoter Stop primary Exon 1 Exon3 Exonk transcrip intron 1 Intron 2 MRNA Exon1 Exon2 Exons S'megG poly-A tail 3 cup no matter where mutain is result in of function can loss gain · , or · loss-of-function ·S amorph (null) no/nonfunctional protein : hypomorph (weak) less normal protein/less activity : Gain-of-function :S Hypermorph (overactive) : excess amount normal protein -Antimorph (dominant negative) : mutant protein prevents normal from working - Neomorph (new function) : mutant protein work diff from normal or normal in wrong context  Genomic DNA Cloning & Sequencing constructing genomic DNA library I Fragmenting genome a cloning fragments. - kinds of breaks 3 s - · Blunt ends : evens-- 5 - 3 · Sticky 5' : S'overhangs Sticky 3' : 3' overhang- 3- 5 2. Purifying Genomic DNA fragments of chosen size class gel electrophoresis -. Insert DNA fragments 3 into cloning vectors to generate library ↓ Isolate individual recombinant clones for sequencing DNA polymerase adds dNTPs to 3'ot of existing molecule ↳ needs & dNTPs · ddNTP inhibit chain elongation dNTP=OH group · ddNTP : Honly-stops chain elongation Sequencing Whole Genome + Annotation putting genome fragments back together · paired-end sequencing enables correct assembly despite repeats - - frequency of stop codon of 3/64N20 codons · average length ORF = , Disease Alleles & Forensics SNP nucleotide polymorphism variation in DNA sea when I nucleotide is different single · = : · SSR = simple sequence repeat , ex : CACACACA Walt every 30 , 000 BP , vary in # of repeat unit PCR : clone of certain any disease an see · exon gene so we can sequence + causing alleles · disease alleles that are SNPs SSRS can be from If or diagnosed by PCR in single cell embryos alleles of SSR loci in junk DNA a unique identifier · are Match probability frequency = of a given CODIS geneotybe ↳ combined in the population DNA Index system people inherit long stretches of SNP alleles · · forensic use : compare SNO alleles in DNA from a crime scene w/ databases of individuals' SNP genotypes Positional PAB Cloning · Testcross : allow to tell which gamete type 2 indiv got from f , anonymous SNPs used InABa S as molecular markers SNP microarrays Parenta Ab/alo millions of SNPs detected using single DNA microarray 3 - Recombinant AB/ab Gene Identification by whole Genome Sequencing to find SNP variant discase causing · 1. Determine whole-genome sea of affected person 2. Compare to human referance seq to find SNP alleles in exons that are different. Compare to dbSNP to 3 identify race SNP alleles 4 filter for SNP alleles to affect function likely gene. Narrow down to 5 one gene allelic heterogenity genetic phenomenon where different mutations in the same gene cause · : a same or simular disease or condition ↳ deafness and of are examples High through - put · DNA sequencing is used to sequence whole genomes ↓ sequence millions diff templates Simultaneously on DNA microarray different than sanger sequencing by - 1.Template attached to solid surface. DNA 2 base time ddNTPs synthesized one at a no - Chromosome Mutation chromosomal rearrangements Deletion -inversion (flips part) - Duplication (double of one part) Translocation (two switch - parts) - Spectral Karyotyping (SKX) = method for Visualizing diff chromosomal rearrangements - Sky probes are PCR productswy floors attached detection gene within chromosomal is haploinsufficant , can consegence mutant if : phenotype mutation · uncover recessive loss-of-function alleles on other homolog chromosomal inversion consequence reduced to unbalanced fertility due · - gametes chromosomal translocation reduced fertility consegence : · Ploidy · Euploid = has integral # of set Monoploid : I set of chromosomes (haploid) Aneuploid - not euploid-mutant · Polyploid Euploid : w) more than 2 Sets (triploid etc), · X = chromosome #in one set Humans X = n = 23 chromosome # in n gametes = meiosis odd ploidy # no gametes by = · triploid = sterile Allopolyploids = hybrids w/ complete chromosome Sets from each parent Human aneuploidy caused by nondisjunction Human Gene Regulation gene expression in eukaryotes can be regulated at any level control of transcription · - Promoters : Basal factors - attract RNA pol 11 to promoter Enhancers : Activators enhance expression can be up or - repressors - - + downstream promoter -chromatin : coactivators + corepressors posttranscriptional gene regulation RNA splicing factors - : Drosophilia Sex differentiation depends on cascade of RNA splicing determined by Sx - small RNAs (miRNAs) regulate translation miRNA-Micro RNA regulate translation mRNA stabilitya · , Epigenetics "programed " epigenetic phenomena - Imprinting = Silenced Insulators : prevent enhancers promoter , organize DNA into loop working · w/ wrong domains called TADs CpG Islands inherited cell division methylation here silences transcription during : - ncRNAs transcript can inhibit transcript of another two can interact to · or gene : prevent translation maternal · + paternal imprinting "Unprogrammed" epigenetic phenomena -intergenerational gametes directly exposed : to Stimuli "remember" change persion after stimulus yone directly exposed "remember" change in gene expression after stimulus transgenerational gametes : not gone - GMOs + Cloning Animals · transgene construct in a test tube that is inserted into an organisms genome a gene = pronuclear injection creates transgenic mice inject DNA into fertilized egg - -implant into mouse uterus transposons are vectors for transgene pharming using transgenic - farm animals to make protein drugs for humans Genome Editing ↓ Gene Therapy Cas9 enzyme cuts DNA at dictated by SgRNA · a site targeted mutagenesis w/ ES cell (embryonicStem cells) · CRISPR/Cas9 - can make knockouts& knocking , generate double stranded breaks in specific genomic locations Genome-edited humans human knocking normal could be created by genome we gene : editing of a zygote Cancer · cancer cell phenotype uncontrolled cell growth immortality - - genomic a Karyotypic instability metastasis