Class Notes (922,334)
CA (542,800)
UTSC (32,897)
BIOC15H3 (28)
Lecture 12

BIOC15Fall2013 Lecture 12 and Lecture 13.docx

9 Pages
133 Views

Department
Biological Sciences
Course Code
BIOC15H3
Professor
Karen Williams

This preview shows pages 1-3. Sign up to view the full 9 pages of the document.
1
BIOC15Fall2013 Lecture 12 Notes: Chromosome mutations and Cancer and Lecture 13 Notes: Cancer and Deletion mapping:
using chromosome mutations
Chromosome mutations
o Variations in chromosome structure or chromosome number
o Variations in chromsomes number:
o Aneuploidy chromosome number is not a multiple of the haploid chromosome #, resulting from loss or
gain of one or more chromosomes, ex: trisomy
o Monoploidy (haploidy) contains one copy of each homolog
o Polyploidy more than the normal diploid number of chromosome sets, ex: triploidy
o Variation in chromosome structure:
o Duplication increase in the number of copies of a chromosomal region
o Inversion 180 degree rotation of a chromosomal region
o Translocation:
Non-reciprocal unequal exchanged between non homologous chromosomes
Reciprocal parts of 2 non homologous chromosome trade places
o Deletion removal of a segment of DNA
o Transposition movement of short DNA segments from one position in the genome to another
Cancer cells and karyotypic instability
o These are changes that produce genomic and karyotypic instability
o Defects in the DNA replication machinery there are higher rates of mutation among cells with defective DNA repair
machinery (mismatch repair and damage repair) because replication error persist
o Increased rate of chromosomal aberrations broken chromosomes, multiple copies of chromosomes, deletions of
large chromosomal segments or a whole chromosome fidelity of chromosome reproduction is decreased in tumour
cells
Types of duplications
o Tandem duplications duplications arranged one after the other (same order or reversed order)
o
o Nontandem (dispersed duplications) same order or reverse order
o
o chromosome breakage can produce duplications
o according to one scenario, nontandem duplications could be produced by insertion of a fragment elsewhere on the
homologous chromosome
o
Unequal crossing over can increase or decrease copy number
o duplication of the X chromosome polytene region 16A causes Bar eyes
o unequal pairins and corssing over during meiosis in females homozygous for this duplication produce chromosomes
that have either one copy of region 16A (normal eyes) or 3 copies of 16A (causing the more abnormal double-bar eyes
o
2
Deletions
o the loss of a segment within one chromosome and the juxtaposition of the two segments on either side of the deleted
segment
o ex: cri du chat syndrome
Inversions
o chromosomal rearrangement in which the chromosome is broken 2x and flipped 180 degrees between being rejoined
o creates loops in polytene chromosomes that reveal the breakpoint of the inversions
o
o in an inversion loop one chromosomal region rotates to conform to similar region in the other homolog
o crossing over with an inversion loop produces aberrant recombinant chromatids
Naming chromosomal aberrations
o Duplication -> Dp(3L) = duplication in left arm of chromosome 3
o In(I) = inversion in chromosome 1
o T(3R) = translocation in the right arm of chromosome 3
o Df(3R) = deficiency in the right arm of chromosome 3
Translocation
o the segment of one chromosome moved to another chromosome
o translocated chromsomes are stained in red and green reciprocal translocation
o
o Robertsonian translocations can reshape genomes reciprocal translocation in acrocentric chromsomes such that
the long chromosome becomes the small one and vice versa
o
Down syndrome and Robertsonian translocation
o one way of getting 3 chromosomes 21 (trisomy 21 which is Down Syndrome) is through translocation between
chromosomes 21 and 14
o so you end up with 2 ‘free’ 21 chromosomes, and the one attached to the 14, making 3 total
3
o
Philadelphia chromosome (Ph)
o associated with chronic myelogenous leukemia (CML)
o used to be called leucocythaemia many white blood cells
o characterized by reciprocal translocation between chromosomes 9 and 22
o
o this rearrangement makes an abnormal hybrid gene composed of part of the c-abl gene and part of the bcr gene
o the hybrid gene encodes an abnormal fused protein that disrupts control of cell division
o The protein encoded by c-abl is a protein tyrosine kinase, an enzyme that adds phosphate groups to tyrosine amino
acids on other proteins.
o This enzyme is an essential part of the set of signals that dictate cell growth and division Normal cells closely
regulate the activity of the c-abl protein, blocking its function most of the time but activating it in response to
stimulation by growth factors in the environment.
o By contrast, the fused protein encoded by bcr/c-abl in cells carrying the translocation is not amenable to regulation
It is always active, even in the absence of growth factor, and this leads to runaway cell division cancer
In a translocation homozygote, chromosomes, segregate normally during meiosis I
o If the breakpoint of a reciprocal translocation do not affect the gene function, there are no genetic consequences in
homozygotes
o
Chromosome pairing in a translocation heterozygote
o in a translocation heterozygote, the two haploid sets of chromosomes carry different arrangements of DNA
o chromosome pairing during prophase I of meiosis is maximized by formation of a cruciform structure 3
segreggation patterns are possible

Loved by over 2.2 million students

Over 90% improved by at least one letter grade.

Leah — University of Toronto

OneClass has been such a huge help in my studies at UofT especially since I am a transfer student. OneClass is the study buddy I never had before and definitely gives me the extra push to get from a B to an A!

Leah — University of Toronto
Saarim — University of Michigan

Balancing social life With academics can be difficult, that is why I'm so glad that OneClass is out there where I can find the top notes for all of my classes. Now I can be the all-star student I want to be.

Saarim — University of Michigan
Jenna — University of Wisconsin

As a college student living on a college budget, I love how easy it is to earn gift cards just by submitting my notes.

Jenna — University of Wisconsin
Anne — University of California

OneClass has allowed me to catch up with my most difficult course! #lifesaver

Anne — University of California
Description
BIOC15Fall2013 Lecture 12 Notes: Chromosome mutations and Cancer and Lecture 13 Notes: Cancer and Deletion mapping: using chromosome mutations Chromosome mutations o Variations in chromosome structure or chromosome number o Variations in chromsomes number: o Aneuploidy  chromosome number is not a multiple of the haploid chromosome #, resulting from loss or gain of one or more chromosomes, ex: trisomy o Monoploidy (haploidy)  contains one copy of each homolog o Polyploidy  more than the normal diploid number of chromosome sets, ex: triploidy o Variation in chromosome structure: o Duplication  increase in the number of copies of a chromosomal region o Inversion  180 degree rotation of a chromosomal region o Translocation:  Non-reciprocal unequal exchanged between non homologous chromosomes  Reciprocal  parts of 2 non homologous chromosome trade places o Deletion  removal of a segment of DNA o Transposition  movement of short DNA segments from one position in the genome to another Cancer cells and karyotypic instability o These are changes that produce genomic and karyotypic instability o Defects in the DNA replication machinery  there are higher rates of mutation among cells with defective DNA repair machinery (mismatch repair and damage repair) because replication error persist o Increased rate of chromosomal aberrations  broken chromosomes, multiple copies of chromosomes, deletions of large chromosomal segments or a whole chromosome fidelity of chromosome reproduction is decreased in tumour cells Types of duplications o Tandem duplications  duplications arranged one after the other (same order or reversed order) o o Nontandem (dispersed duplications)  same order or reverse order o o chromosome breakage can produce duplications o according to one scenario, nontandem duplications could be produced by insertion of a fragment elsewhere on the homologous chromosome o Unequal crossing over can increase or decrease copy number o duplication of the X chromosome polytene region 16A causes Bar eyes o unequal pairins and corssing over during meiosis in females homozygous for this duplication produce chromosomes that have either one copy of region 16A (normal eyes) or 3 copies of 16A (causing the more abnormal double-bar eyes o 1 Deletions o the loss of a segment within one chromosome and the juxtaposition of the two segments on either side of the deleted segment o ex: cri du chat syndrome Inversions o chromosomal rearrangement in which the chromosome is broken 2x and flipped 180 degrees between being rejoined o creates loops in polytene chromosomes that reveal the breakpoint of the inversions o o in an inversion loop one chromosomal region rotates to conform to similar region in the other homolog o crossing over with an inversion loop produces aberrant recombinant chromatids Naming chromosomal aberrations o Duplication -> Dp(3L) = duplication in left arm of chromosome 3 o In(I) = inversion in chromosome 1 o T(3R) = translocation in the right arm of chromosome 3 o Df(3R) = deficiency in the right arm of chromosome 3 Translocation o the segment of one chromosome moved to another chromosome o translocated chromsomes are stained in red and green  reciprocal translocation o o Robertsonian translocations can reshape genomes  reciprocal translocation in acrocentric chromsomes such that the long chromosome becomes the small one and vice versa o Down syndrome and Robertsonian translocation o one way of getting 3 chromosomes 21 (trisomy 21 which is Down Syndrome) is through translocation between chromosomes 21 and 14 o so you end up with 2 ‘free’ 21 chromosomes, and the one attached to the 14, making 3 total 2 o Philadelphia chromosome (Ph) o associated with chronic myelogenous leukemia (CML) o used to be called leucocythaemia  many white blood cells o characterized by reciprocal translocation between chromosomes 9 and 22 o o this rearrangement makes an abnormal hybrid gene composed of part of the c-abl gene and part of the bcr gene o the hybrid gene encodes an abnormal fused protein that disrupts control of cell division o The protein encoded by c-abl is a protein tyrosine kinase, an enzyme that adds phosphate groups to tyrosine amino acids on other proteins. o This enzyme is an essential part of the set of signals that dictate cell growth and division  Normal cells closely regulate the activity of the c-abl protein, blocking its function most of the time but activating it in response to stimulation by growth factors in the environment. o By contrast, the fused protein encoded by bcr/c-abl in cells carrying the translocation is not amenable to regulation  It is always active, even in the absence of growth factor, and this leads to runaway cell division  cancer In a translocation homozygote, chromosomes, segregate normally during meiosis I o If the breakpoint of a reciprocal translocation do not affect the gene function, there are no genetic consequences in homozygotes o Chromosome pairing in a translocation heterozygote o in a translocation heterozygote, the two haploid sets of chromosomes carry different arrangements of DNA o chromosome pairing during prophase I of meiosis is maximized by formation of a cruciform structure  3 segreggation patterns are possible 3 o o balanced gametes are produced by alternate segregation and not by adjacent 1 or adjacent 2 segregation Reciprocal interchromosomal translocation o position effect: the expression of the gene changes because of its changed position in the genome o o When a chromosomal rearrangement such as an inversion of a segment of DNA places the gene next to highly compacted heterochromatin near the centromere, the gene's expression may cease  gene expression may be silenced in some cells and not in others Burkitt Lymphoma o Associated with reciprocal translocation between chromosomes 8 and 14 o Charachterized by change in neighbours for the MYC gene leading to cell growth and division that is not controlled (cancer) o Cancer o uncontrolled growth in a mass of cells may result in transformation such that the cell growth is no longer restrainged by contact inhibition  oncogenesis o cell cycle is controlled by the concentration of cyclin-dependent kinases at regular checkpoint  control activity of other proteins by phosphorylating them o we are going to consider: proto-onco genes, tumor suppressor genes, mutator genes o cancer producing mutations are of 2 general types 4 o o oncogene  a gene whose action stimulated unregulated cell proliferation o example 1: on the Ph chromosome, ABL gene within new location gives BCR-ABL oncogene that expresses a tyrosine kinase continuously  this causes growth of white blood cells o example 2: Burkitt lymphoma MYC oncogene in the translocation is overexpressed leading to uncontrolled growth o example 3: c-kit (cellular in this case canine kit) is a truncated protein tyrosine kinase involved in osteosarcoma in dogs (bone cancer) o tumour suppressor genes  suppress the normal cell growth if mutated they lead to uncontrolled cell growth o example retinoblastoma RBI Evidence from mouse models that cancer is caused by several mutations o transgenic mice with dominant mutations in the myc gene and in the ras gene = increased mutation rate when mutation found in both genes and earlier onset of cancer due to that o the myc oncogene produces tumours slowed than the ras oncogene but when put together, the rate is higher than either one on their own o o mice with recessive mutation in the p53 gene  heterozygous individual have a later onset i
More Less
Unlock Document


Only pages 1-3 are available for preview. Some parts have been intentionally blurred.

Unlock Document
You're Reading a Preview

Unlock to view full version

Unlock Document

Log In


OR

Don't have an account?

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


OR

By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.


Submit