Page 61 - Mouse Molecular Genetics

Full Abstracts
Program number is above title. Author in bold is the presenter.
that genes located near pore complexes have enhanced expression than genes in nuclear interior. Last data about simultaneously
transcribed genes showed that distance between such genes is around 80000 bp.(Goetze,MBC, 2007, 27, 4475) and support
data of Cook (1995) describing chromatin loops with an average contour length of 86 kbp.
Demonstrating Resistance-Mitigrating Effect of Artemisia Annua Phytochemical Blend with in-Vitro Cultures of
Plasmodium Falciparum and in-vivo with Plasmodium Berghei Anka in Mice. Kangethe N Lucy
Ahmed Hassanali
Sabah Omar
Nganga Joseph
Kinyua Johnson
. 1)
COLLEGE, NAIROBI, Kenya P.O BOX 52428--00200; 2) AHMED HASSANALI International Centre of Insect Physiology
and Ecology P.O BOX 30179 Nairobi, Kenya; 3) SABAH OMARKenya Medical Research Institute P.O BOX 54840-00200
Nairobi, Kenya; 4) JOSEPH K NGANGA Jommo Kenyatta University of Agriculture and Technology P.O BOX 62000
Nairobi,Kenya; 5) JOHNSON KINYUA Jommo Kenyatta University of Agriculture and Technology P.O BOX 62000
ABSTRACT Resistance of Plasmodium falciparum to drugs such as chloroquine and sulfadoxine-pyrimethamine is a major
problem in malaria control. Artemisinin derivatives, particularly in combination with other drugs, are thus increasingly used to
treat malaria, reducing the probability that parasites resistant to the components will emerge. Although stable resistance to
artemisinin has yet to be reported from laboratory or field studies, its emergence would be disastrous because of the lack of
alternative treatments. The project was designed to demonstrate resistance-mitigating effects of phytochemical blend of
Artemisia annua relative to pure artemisinin against the malaria parasite Plasmodium falciparum and on rodent malaria parasite
Plasmodium berghei Anka. For the in vitro experiments selection was undertaken on two cultures of P. falciparum D6 (CQ-
sensitive strain from Sierra Leone) and W2 (CQ-resistant strain from Indochina), by exposing them to A. annua phytochemical
blend and the pure artemisinin over 50 cycles at doses initially required to give 50% mortality (IC50) of the parasites. Dose-
response effects of the blend and the pure compound were determined after 10, 20, 30, and 40, cycles and compared to see if
significant difference developed in their efficacy in causing mortality of the parasites. The in vivo experiments mice have been
done by inoculating the Swiss mice with the P. berghei ANKA parasite and thereafter treated them with the test drugs. After 4
days the mice were passaged and parasitaemia determined to calculate the ED50 and the ED9O. The ED50 and ED90 got for
artemisinin with P. berghei ANKA was 1.43 and 7.18 mg/ respectively while the ED50 and ED90 got for the blend with P.
berghei ANKA was 34.5 and 118 mg/
Subtelomere recombination is frequent in B-cell lymphomas lacking telomerase. Tammy A. Morrish
Joshua Budman
Stephen Dria
Vivek Behera
Margaret Strong
Sarah Wheelan
Carol Greider
. 1)
Molecular Biology and Genetics, Johns
Hopkins University, Baltimore, MD; 2) Biomedical Engineering; 3) Oncology and Biostatistics.
Telomere maintenance mechanisms are necessary for tumor growth and are typically achieved by the enzyme telomerase.
However, some tumors lack telomerase and rely on recombination-based mechanisms for telomere maintenance. When
telomerase is deleted in yeast, multiple mechanisms of break-induced replication (BIR) are necessary to maintain the telomeres
and depend on either Rad50 or Rad51. BIR may also occur within telomere or subtelomere sequences. To examine whether BIR
occurs in mammalian cells, we are using a mouse B-cell lymphoma model, myc+mTR-/-. Tumors from this model were used in a
FISH based assay and detected subtelomere recombination at elevated frequencies in tumors lacking telomerase. To specifically
focus on whether subtelomere recombination contributes to telomere maintenance, we are utilizing comparative genomic
hybridization (aCGH) to determine the frequency and location of copy number changes within the subtelomere. With these arrays
we detect an elevated frequency of copy number changes within the subtelomeres of some tumors lacking telomerase when
compared to primary tissues, including primary B-cells or when compared to myc+mTR+/+ tumors. Furthermore, we find many
of the breakpoints within the subtelomere occur at specific sites within the subtelomere. At some subtelomeres we observe
extensive regions of amplification (20kb) while at other subtelomeres we observe small, dispersed regions of amplification. We
are currently verifying whether this occurs within specific types of repetitive sequences and whether Rad50 contributes to the
frequency of these events. Overall, these studies focus on the mechanisms of subtelomere recombination in tumors lacking
Evolution of Dosage Compensation of the Mammalian Active X Chromosome. Di Kim Nguyen
Xinxian Deng, Christine
Disteche. Pathology, University of Washington, Seattle, WA.
In mammals, X-linked gene expression is adjusted by regulatory mechanisms to compensate for the evolutionary loss of Y-
linked genes and balance gene expression in both sexes. Based on analyses of RNA-sequencing datasets, we confirmed our
previous findings that expressed genes on the X chromosome are upregulated compared to autosomal genes in five tissues in 14
species (12 eutherian and 2 metatherian mammals). We then compared the current X genes in mammals against the proto-X-
autosomal genes in chicken and opossum- and arrived at a similar conclusion. Finally, we showed that X-linked genes in female
mammals overall have gained more expression than that in males over evolutionary time in a tissue-specific manner such as in
the brain, liver, and sex organs. Differential expression between the sexes may be due either to escape from X inactivation in
females or to mutations preferentially selected on the X because the X chromosome spends 2/3 of its time in females.