Chapter 7 mutations
Below: not in text as a sequence .... mutations.html
gene and chromosomal mutations
forward and back mutations
somatic; germinal;
timing of mutations;
early or late in the development of
an organism EarlyLateMuts.gif
types of mutations
Detection systems for a specific gene:
Tradescantia KU-9
from blue to pink
a triploid; B = blue, b= pink; KU-9 is Bbb
KU-9 flowers .........ku9-1.GIF
KU-9 staminal hairs .......KU9-3.GIF
Ichikawa, S., et al. 1996 Yearly variation of spontaneous
somatic mutation frequency in the stamen hairs of Tradescantia
clone KU 9 grown outdoors, which showed a significant increase
after the Chernobyl accident. Mutat Res 349(2): 249-59.
Detection systems for genes on the x-chromosome:
By Herman Muller, student of T. H. Morgan
ClB technique ..... as a sequence... ClBsequence.html
hand out...............ClB01.GIF
the genes ..............ClB02.GIF
the genotypes ........ClB03.GIF
Punnett square .......clb04.GIF
Jenny and Paul ...............ClB05.GIF
Paul and his sperm ............... ClB06.gif
Jenny and her eggs ............... ClB07.GIF
Three of Jenny and Paul's Daughters
Nancy ............... ClB08.GIF
Leanne ............... ClB09.GIF
Danielle ............... ClB10.GIF
conclusion .............ClB11.GIF
Note on the ClB cartoon that the proportion of
x-bearing sperm with mutation m is the same as the proportion of
F-1 bar eyed females which do not have sons.
Review of ClB via a problem
another problem .....clb12.gif
Muller's Graph ....
Muller Nobel Prize 1946....Photos.... MullerPhotos.GIF
(not web)
Muller and sperm banks:
"The widow of Nobel Prize-winning geneticist
Hermann J. Muller says she is upset a California businessman
named a sperm bank after her husband. Tea Muller said yesterday
in Bloomington Ind., she had denied use of her husband's name
for the project - the Hermann J. Muller Repository for Germinal
Choice - which matches genes of Nobel Prize-winning scientists
with bright women. Robert K. Graham of Escondido, Calif., who
established the sperm bank, has......."
Boston Globe 4 March 1980
http://www.boston.com/globe/search/stories/Nobel/1980/1980ar.html
Muller became involved with communism and the Soviet Union; There
is an interesting story of genetics in the Soviet Union at that time:
Read the book by Medvedev if interested.
Medvedev, Ahores A. 1969 The rise and fall of T.D. Lysenko.
Columbia University Press
More recently: Effect of low level radiation
Greene, G. 1999. The woman who knew too much: Alice
Stewart and the secrets of radiation. The University of Michigan
Press, Ann Arbor.
"In 1956, British physician Alice Stewart
discovered that exposing a fetus to a single diagnostic X-ray
doubles the risk of an early death from cancer." .....
http://www.alicestewart.org/
And chemical mutagenesis: Charlotte Auerbach (1899-1994)
Genetics 1995 141: 1-5.
above: not in text
3 February 2003
Exams returned on Wednesday
Can not answer questions at end of the exam time
Why study chromosome mutations?
use in genetics - as with the ClB technique; the C
property consists of paracentric inversions; B of a duplication;
Bridges and Mrs Morgan in nondisjunction
in medicine - high frequency in cancer cells (as page 162-164
in text)
in study of evolution - species differ in chromosome number
and gene arrangement (Lonnig, W. E. and H. Saedler (2002).
Chromosome rearrangements and transposable elements. Annu Rev
Genet 36: 389-410.
"It is already clear that chromosomal and genic rearrangements
including inversions, translocations, insertions, deletions, and
duplications are an extremely common feature of evolution of the
genome." .... Lewontin, R. C. (2002). "Directions in evolutionary
biology." Annu Rev Genet 36: 1-18.
Chromosome structural mutations
We will look at some of the major chromosome mutations.
As a way of keeping tract and comparing them I ask you to fill in
the chromosome mutation chart on page
37 of the workbook. The chart is compressed, so you may wish to
make a larger copy. In lecture I will discuss the chart items.
Hopefully, you will be able to fill in the chart on your own after
listening to the lectures, observing the lecture materials and
studying the web materials.
Workbook page 35-36: We may manipulate ideograms of chromosomes
to get some idea about how real karyotypes will look.
For example, here is a comparison of cartoon and real chromosomes
in karyotypes
There is an ideogram exercise in the workbook page33
Toolbox for chromosome mutations - set of rules/
observations
chromosomes pair in twos
mitotic chrmosomes are not paired; best observed if
banded
polytene chromosomes are paired, long, wide and banded
mutant configurations seen in the heterozygote and the paired
chromosomes of pachytene and polytene
learn to match numbers on two, three or four lines
learn some patterns
use of clay to help visualize chromosome patterns
Must know meiosis
* * * * Flow of analysis: model to pachytene configuration to
anaphase-I to gametes.
Kinds of chromosomes
more polytene chromosomes... polytenes.gif
advantages and disadvantages of each type of
chromosome?
The human geneticist is usually limited to an analysis of
mitotic chromosomes. Why?
Chromosome markers
euchromatin and heterochromatin
simple statement: during interphase euchromatin
is diffuse and lightly stained; during interphase
heterochromatin is tightly coiled and stains darkly.
mitotic banding...
Centromeric heterochromatin . C-banding.gif
to see this picture on your computer check out:
Univ
Washington Pathology ...a beautiful Web site on
chromosome banding
Chromosome mutations
Overview
change may be within or between chromosomes
mutation may be homozygous or heterozygous
peculiar structures may be seen in heterozygotes for paired
chroms.
IMPORTANT: Paired chromosomes are best for detection of
chromosome mutations !!!!!!!!!!!!!!!!!!!!!!!!!!!
animations of the 6 structural mutations
The mutations
deletion..... 
acentric fragment is lost
deletion loop in polytene... Fig 7...... 07-2.gif
Cat cry karyotype (not on web) CriDuChat.gif
"Cri-du-chat syndrome was first described by Lejeune et
al. (1963) as a hereditary congenital syndrome associated
with deletion of part of the short arm of chromosome 5. The
deletions can vary in size from extremely small and
involving only band 5p15.2 to the entire short arm. Although
the majority of deletions arise as new mutations,
approximately 12% result from unbalanced segregation of
translocations or recombination involving a pericentric
inversion in one of the parents." "The cri-du-chat syndrome
appears to be one of the most common human deletion
syndromes, with an incidence varying between 1 in 20,000 to
1 in 50,000 births (Niebuhr, 1978). The frequency in
populations of profoundly retarded patients (IQ less than
20) is approximately 1% (Niebuhr, 1978)." Ref: OMIM
Duplications
Duplication and Deletion via unequal crossing over ...
UnequalXover.gif
Unequal crossing over in Drosophila
Bar eye.model unequal x-over
Bar eye polytenes... Fig 7.5 ...... 07-5.gif
as a source of new genes
5 February 2003
mid term correction form handed out on Friday
First part of recitation for new materials; second part to go
over the exam
Exam results
Second exam ... 21 February ... chapters 7 through 11
Review
Inversions
paracentric inversion (centromere not
within inverted segment)
crossover in loop
Effect of crossover within loop .....Fig 7.7 ....
07b.gif
bridge and fragment... A simple animation of bridge and
fragment.
***********If a crossover occurs in the loop, the
crossover products will not be recovered in the test cross
progeny. It is as if crossovers were suppressed. Are they
really suppressed?
C of ClB is not true crossover suppression, but the lack of
recombination in male Drosophila certainly is crossover
suppression.
complete paracentric inversion story
if x-over in loop
at anaphase-I: bridge and fragment configuration
at end of meiosis:
from the may apple....... podo9a.JPG
pericentric inversion (centromere within inverted
segment)
genotypes (note shift of centromere) ....PeriInversion2.GIF
results of crossover in loop .......Fig 7.8 .... 7-8.gif
We have seen an inversion before ....comparison of XIC
(X Inactivation Center) in mouse and human.... Xinactivation1.gif
between chromosome mutations:
translocation
models for reciprocal
translocation (not showing
4-strandedness; also not showing chiasmata)
1a.Derivation of
translocations animation
2.
Pairing into quadrivalent at
pachytene
3.
Adjacent and alternate
segregation (metaphase-I)
4. Adjacent segregation
(metaphase-I)
5. Adjacent and to
poles (anaphase-I)
6. Adjacent at end of
ana-I
7. Alternate segregation
(metaphase-I)
8. .Alternate to poles
(anaphase-I)
9. Alternate at end of
ana-I
10. Adjacent segregation,
metaphase-I
11. Alternate,
metaphase-I
review .......text Fig 7.10
zig-zag best with pop beads
translocation heterozygote problems
Importance of spindle fiber arrangement and chiasmata
animation of alternate segregation.. TransAnimation.gif
7 February 2003
Complete chapter 7 and on to chapter 8
An interesting and important translocation story is the disease
Chronic Myelogenous Leukemia (CML)
Note Philadelphia chromosome in text Figure 7.11..... 7x11.gif,
the result of a reciprocal translocation betwee chromosomes 9 and 22
resulting in leukemia, now treated with a drug STI-571. There are "at
least 94 disease related translocation gene-fusion partners in
neoplastic disorders." Science 291: 1224.
The fusion protein activates cell activities normally working
when cell is stimulated by a growth factor. One activity is an
increase in the rate of mitosis. This leads to an increase in the
number of cells with the Philadelphia chromosome and we have the
chronic phase of the disease.
Another mutation will cause one of these cells to start
undergoing mitosis at a high rate and lead to CML
The drug Gleevec essentially inactivates the fusion
product.
Picture of Brian Druker .not on web... Druker.gif
In about 90% of patients treated there is no further
progression of the disease.
References
Discussion of heterochromatin: Facultative and Constitutive.
(important to know these)
euchromatin and heterochromatin
simple statement: during interphase
euchromatin is diffuse and lightly stained; during
interphase heterochromatin is tightly coiled and stains
darkly.
Robertsonian translocations; a special kind of reciprocal
translocation
see text, Fig 7.16
1. Models for formation
1a. The genotypes
2. The chromosomes and pairing
3. Normal and abnormal distribution of chromosomes
21-21 Robertsonian translocation.(not on web). Robertsonian21-21.gif
For chromosome number changes via Robertsonian
translocations
Chromosome number mutations
euploidy (popyploidy; sets of chromosomes)
autoploidy (one species)
autotetraploidy via colchicine
may be fertile or sterile, related to pairing, species
variation
triploidy via double fertilization
alloploidy (more than one species)
allotetraploidy (2n + 2n, two species)
Karpechenko
Karpechenko, Vavilov, Dobzhanksy photo...
Karpechenko.GIF..not
on web
hexaploid wheat
aneuploidy (individual chromosomes; 2n + or - chroms)
normal and abnormal disjunction (see
movie page)
idea of two by two chromosome pairing in
meiosis
nondisjunction
first division...
second division.
examples
XYY
Turner Syndrome (XO).
Klinefelter Syndrome (XXY)
Down Syndrome (trisomic 21).
Table 7.2
Comparison of mammalian chromosomes..not on web;..... Exhibit
8x37 reduced.gif
mention Susumu Ohno
Importance of mutations in agriculture