28 1. לאדם 2. לחיידק 3. אין מספיק מידע 4. לשניהם Tm זהה שאלה: אורך הגנום ההומני הוא 3 טרליון זווגי בסיסים, לעומתו אורך הגנום של חיידק ה-e. coli הוא 1.5 מיליון זיווגי בסיסים. הגנום ההומני מורכב מ-47% זיווגי בסיסים של GC ולעומתו הגנום של החיידק בעל 52% של GC. למי טמפרטורת Tm יותר גבוה?1. לאדם2. לחיידק3. אין מספיק מידע4. לשניהם Tm זהה
36 Humans (H. sapiens) and bonobos (P Humans (H. sapiens) and bonobos (P. paniscus) share a cryptic microsatellite element in the 5' regulatory region of AVPR1A, which is absent in the chimpanzee (P. troglodytes).
40 Fundamental properties of genes Genes are heritable units, arranged linearly along chromosomes.Complementation analysis of a large number of mutants defines genes that determine a function.E.g., biosynthetic pathway or DNA replication.Genetic techniques in microorganisms were used to determine the fine structure of a gene.Genes encode polypeptidesCodons are triplets of nucleotides that encode an amino acid.
48 Human genome 2.91 billion base pairs 24,000 protein coding genes (~32,000 non-coding genes)1.5% exons (127 nucleotides)24% introns (~3,000 nucleotides)75% intergenic (no genes)Average size of a gene is 27,894 basesContains an average of 8.8 exonsTitin contains 234 exons.
49 List of 68 eukaryotes, 141 bacteria, and 17 archaea at Sample genomesSpeciesSizeGenesGenes/MbH.sapiens3,200Mb35,00011D.melanogaster137Mb13.33897C.elegans85.5Mb18,266214A.thaliana115Mb25,800224S.cerevisiae15Mb6,144410E.coli4.6Mb4,300934 List of 68 eukaryotes, 141 bacteria, and 17 archaea at
50 What does the Genome tell us? Estimated number of genes ~32,000Only 1 to 1.5% of the genome encodes proteins75% of the genome is not transcribed46% is repetitive DNAJUNK DNA –the fodder/history of evolutionRecombinationDiversity“genomic” disease
52 We humans are 99.9% identical at the DNA sequence level There are still ~3 million nucleotide differences among us called SNPs (60,000 within the exons)---that presumably account for differences in disease susceptibility, drug responses, etc.Polymorphic variation between and within populationsImplications for concepts of “race,” “individuality”
56 Duchenne Muscular Dystrophy ניוון שריריםMOLECULAR BIOLOGY OF THE DISEASEDuchenne Muscular Dystrophy is one of more than twenty different types of muscular dystrophy. The Duchenne type affects only boys and is known to result from a defect in a single important protein in muscle fibers called Dystrophin. The muscle fiber will break down if the Dystrophin is missing and is unable to function properly. As a result, the reduction in the number of good muscle fibers and the whole muscle becomes weak.
57 כמה מחלות גנטיות יכולות להיות? 1. לא יותר מ-1002. כ-1000 מחלות3. כ מחלות4. כמספר הגנים.
71 A model for the structure of an interphase chromosome
72 Position Effects on Gene Expression Heterochromatin: condensed Euchromatin: loose
73 Speculative Model for the heterochromatin at the ends of yeast chromosomes Sir: Silent information regulator binding to unacetylated histone tails
74 Speculative Model for the heterochromatin at the ends of yeast chromosomes DNA-binding proteins recognize DNA sequence close to telomere, recruit Sir proteins and cause histone tail modification, forming heterochromatin
75 Two speculative models for how the tight packaging of DNA in heterochromatin can be inherited during chromosome replication
84 Condensin plays important roles Chromatin PackingCondensin plays important roles
85 The SMC (Structural Maintenance of Chromosomes) proteins in condensins
86 Selective localization of two interphase chromosomes Chromosome 18 (red) and 19 (turquoise)
87 Specific regions of interphase chromosomes in close proximity to the nuclear envelope Two different regions of chromosome 2 (yellow and magenta) close to the nuclear envelop (green)
88 SummaryChromosomes are decondensed during interphase and hard to visualizeLampbrush chromosomes of vertebrate oocytes and polytene chromosomes in the giant secretory cells of insects are exceptions, revealing the global organization of chromosomeGene expression needs the decondensation of chromosome loopsEuchromatin and heterochromatinTelomere and centromere are general heterochromatinChromosomes are spatially organized and deposited in nucleusMitotic chromosomes are condensed and organized.
90 DNA Molecules are highly condensed in chromosomes Nucleosomes of interphase under electron microscopeNucleosome: basic level of chromosome/chromatin organizationChromatin: protein-DNA complexHistone: DNA binding proteinA: diameter 30 nm; B: further unfolding, beads on a string conformation
128 מבנה של כרומוזום במיקרוסקופ אלקטרוני מבנה של כרומוזום במיקרוסקופ אלקטרוני
129 4 46 Human 32 Yeast 42 Macaque 40 Mouse 38 Cat 48 Potato 26 Frog 20 Total number of chromosomes/somatic (body) cell4Penicillin mold46Human32Yeast42Macaque40Mouse38Cat48Potato26Frog20Algae16PlanariaCorn8Fruit flySpeciesThere is no connection between the number of chromosomes and the genome size, gene content, or any other feature of genomes. It is and essentially independent characteristic.Dog78
130 Myrmecia pilosula Smallest number of chromosomes known in a eukaryote: 1 pair (2 total per somatic cell)Myrmecia pilosula
131 Ophioglossum reticulatum, a fern Largest number of chromosomes known in a eukaryote:630 pairs (1260 total per somatic cell)Ophioglossum reticulatum, a fern
136 Chromosomal fragile sites are loci that are especially prone to forming gaps or breaks on metaphase chromosomes when cells are cultured under conditions that inhibit DNA replication or repair. The relationship of "rare" folate sensitive fragile sites with (CCG)n expansion and, in some cases, genetic disease is well established.
137 Fragile X syndromeWhat is Fragile X syndrome? Fragile X syndrome is the most common inherited cause of mental impairment, affecting approximately 1 in 2,000 males and 1 in 4,000 females worldwide.Cytogenetic analysis of metaphase spreads demonstrates the presence of the fragile site in less than 60% of cells in most affected individuals.).In 1991, the fragile X gene (FMR1) was characterized and found to contain a tandem repeated trinucleotide sequence (CGG) near its 5' end. The mutation responsible for fragile X syndrome involves expansion of this repeat segment. The number of CGG repeats in the FMR1 genes of the normal population varies from six to approximately 50. There are two main categories of mutation, premutations of approximately 50 to 200 repeats and full mutations of more than approximately 200 repeats. There is no clear boundary between the upper limit of normal and the lower limit of the premutation range. For this reason, alleles with approximately copies of the repeat are said to be in the "grey zone." Some alleles in this size range are unstable and expand from generation to generation, while others are stably inherited. A premutation is susceptible to expansion after passage through a female meiosis. The larger the size of a woman's premutation, the more the risk of expansion to a full mutation in her offspring..