dsDNA כיווניות קשר פוספו A:T and G:C = 10 -10.
-
date post
22-Dec-2015 -
Category
Documents
-
view
220 -
download
0
Transcript of dsDNA כיווניות קשר פוספו A:T and G:C = 10 -10.
שאלת תירגול: מדוע בחרת ללמוד רפואה
. אני מעוניין לעזור לאנושות1•
. הנושא מעניין2•
. קידום אישי3•
. המשפחה לחצה4•
שניות לענות תשובה!30יש לך •
טרליון זווגי בסיסים, לעומתו 3שאלה: אורך הגנום ההומני הוא מליון זיווגי בסיסים. 1.5הוא e. coli aאורך הגנום של חיידק ה- ולעומתו GC זיווגי בסיסים של 47%הגנום ההומני מורכב מ-
יותר Tm. למי טמפרטורת GC של 52%הגנום של החיידק בעל גבוה?
. לאדם1•
. לחיידק2•
. אין מספיק מידע3•
זההTm. לשניהם 4•
Less complex DNA renatures fasterDNA 1 DNA 2 DNA 3
ab
cdefghijklmnopqrstuv
izyajczkblqfreighttrainrunninsofastelizabethcottonqwftzxvbifyoudontbelieveimleavingyoujustcountthedaysimgonerxcvwpowentdowntothecrossroadstriedtocatchariderobertjohnsonpzvmwcomeonhomeintomykitchentrad
ab ab ab ab
ab ab ab ab ab
ab ab ab ab ab
ab ab ab ab ab
ab ab ab ab ab
ab ab ab ab ab
ab ab ab ab ab
ab ab ab ab ab
etc.
cdefghijklmnopqrstuv
cdefghijklmnopqrstuv
cdefghijklmnopqrstuv
Molar concentration of each sequence:150 microM 15 microM 1.5 microM
For an equal mass/vol:
Census of human repeats
IHGSC. Nature (2001) 409 860-921
Over 40% of the human genome corresponds to interspersed repeats
Types of DNA in each kinetic componentHuman genomic DNA: kinetic components and classes of sequences
0
0.25
0.50
0.75
1.00
fra
ctio
n r
ea
sso
cia
ted
10 10 10 10 10 10 10 10 10 10 102 3 410-1-2-3-4-5-6 510
About a million copies of Alu repeats, each 0.3 kb
About 50,000 copies of L1 repeats (0.2 to 7 kb in length), plus 1000 to 10,000 copies of at least 10 other familes of interspersed middle repetitive DNA (e.g. THE LTR repeats)
Thousands of copies of rRNA genes
About 50,000 to 100,000 "single copy" genes
C to
"Foldback"
Human genomic DNA
מבנה הכרומוזום בשלב חלוקת התא
גן – אזור ב-ד.נ.א מימנו מתורגמת מולקולת ר.נ.א בעלת פעילות ביולוגית
Gene 3
אינטרונים – רצפים שמוסרים
בגרעין ולא נשארים
במולקולת הרנא הבוגר
אקסונים – רצפים
שנשארים במולקולת הרנא
הבשלה
אינטרונים נמצאים רק באוקריוטים
פרומוטר אקסון
אינטרון
רצף – שנשאר ברנא לאחר העיבוד ועובר לציטופלזמהאקסוןרצף – המוסר מהרנא בגרעיןאינטרון
מהם הכרומוזומים?
. אתרי עיגון של הדנא בגרעין1•
. מבנה הגרעין2•
. מיכלי אריזה של הדנא3•
. מיכלי אריזה של החלבונים4•
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 bases
Contains an average of 8.8 exons
Titin contains 234 exons.
Human genome
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 populations
• Implications for concepts of “race,” “individuality”
MOLECULAR BIOLOGY OF THE DISEASE
Duchenne 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.
Duchenne Muscular Dystrophy
שרירים ניוון
The bending of DNA in a nucleosome1. Flexibility of DNAs: A-T riched minor groove inside and G-C
riched groove outside2. DNA bound protein can also help
Covalent Modification of core histone tails
Acetylation of lysines (K)Mythylation of lysines
Phosphorylation of serines (S)
Histone acetyl transferase (HAT)
Histone deacetylase (HDAC)
Acetylation
Mythylation
HDAC activity
אפיגנטיקה
4Penicillin mold46Human
32Yeast42Macaque
40Mouse
38Cat
48Potato26Frog
20Algae16Planaria
20Corn8Fruit fly
SpeciesSpecies
Total number of chromosomes/somatic (body) cell
Dog 78
There 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.
Smallest number of chromosomes known in a eukaryote:1 pair (2 total per somatic cell)
Myrmecia pilosula
Largest number of chromosomes known in a eukaryote:630 pairs (1260 total per somatic cell)
Ophioglossum reticulatum, a fern
Cockayne syndrome group B (CSB) cells that fail to express CSB protein which causes profound neurological and developmental defects
ה DAPIצביעת לגן- DNAשל סמן (נקודה לבנה)עם
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 .
Fragile X syndrome
What 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 45-55 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 ..