Questions – Gene Regulation
Questions 1-4 are based on the PNAS article entitled “Regulation of gene expression in the
mammalian eye and its relevance to eye disease” by Scheetz et al. (2006).
1.
This is a multi-part question. To answer it, you will need to go to www.ncbi.nlm.nih.gov and follow these
instructions.
From the drop-down search menu, choose “Nucleotide.” Type abca4 in the box to the right and hit “Search”.
Click on the Xenopus
abca4 gene (second entry). On the
right side of the page, click “Run BLAST.” On the next page, click the BLAST
button at the bottom (and wait…).
- Scroll down your results
page. What other taxa (scientific
and common names) share some sequence identity with this Xenopus gene?
Gallus gallus (Red
Junglefowl),
bos taurus
(domestic cow),
sarcophilus
harrisii (tasmanian devil),
trichechus manatus
(West Indian Manatee)
- What is Xenopus?
Xenopus is a genus of highly
aquatic frogs native to Sub-Saharan Africa.
In an evolutionary sense, why study
gene regulation in this animal?
It makes sense to study these
animals because of their close evolutionary relationship with humans when
compared to other model organisms. Also, they are only vertebrate model system
that allows for in vivo analyses of gene function as well as biochemistry.
Why study it in rats, as they do in
your paper?
The authors of our paper cite six
criteria that they looked for in choosing a species for their experiment. They
are: 1) to be highly inbred 2) to be commercially available it otherwise
readily available from academic institutions 3) to have widely diverse genetic
origins 4) to have genotypic data available so that genetic diversity between
strains and the degree of inbreeding within strains could be assessed and so
that informative markers could be selected for the mapping cross 5) to be
robust breeders, and 6) to be free of early-onset systematic phenotypes or
degenerative eye phenotypes. Presumably, the rat strains that the authors
selected met all of these criteria. Furthermore, rats make a good candidate for
studies in gene regulation because they are cheap and their cellular processes
of gene transcription and translation are analogous enough to those of humans.
- What does wild type abca4 do in these animals? Why is it conserved across so many
disparate species?
Wild type abca4 codes for a
retina-specific membrane-bound protein that acts as a flipase enzyme that is
only found in multicellular eukaryotes. This enzyme transports ATR and NR-PE
from the extracellular membrane surface to the intracellular membrane surface
in retina photoreceptor cells. Mutations in this gene cause early-onset macular
degeneration (genecards.org).
Abca4 is conserved across many
different species due to the early development of this gene and the eye in eukaryotes
(nih.gov).
2.
What does the mutated abca4 allele cause in humans?
The mutated abca4 allele causes
the autosomal-recessive disease called Stargardt macular dystrophy (STGD).
Stargardt disease is one of the more common forms of heritable blindness among
children and young adults.
3.
How does correlated expression of genes like the
BBS genes in this study indicate gene regulation?
If
genes share a strong correlation in that they are often mutually expressed at
the same time, then it follows that they are co-regulated as well. The
mechanisms in place that causes one gene to be regulated (expressed more or
less) may be the same mechanism in place that regulates another gene. These
co-regulated genes would then appear as correlated genes as well.
4.
What are microarrays? What do they have to do with the goal of
DNA@home?
DNA Microarrays are small, solid supports
onto which the sequences from thousands of different genes are immobilized, or
attached, at fixed locations. A microarray works by exploiting the ability of a
given mRNA molecule to bind specifically to the DNA template from which it
originated. By using an array containing many DNA samples, scientists can
determine, in a single experiment, the expression levels of hundreds or
thousands of genes within a cell by measuring the amount of mRNA bound to each
site on the array.
The ultimate goal of
DNA@Home is to discover what regulates the genes in DNA. Thus the discovery of
microarrays makes it possible
to perform a number of experiments that examine the expression of thousands of
genes in a large number of related individuals and to use this data to identify
the chromosomal locations of the genetic elements that are responsible for the
variation in gene expression among individuals. This technology will also aid
the examination of the integration of gene expression and function at the
cellular level, revealing how multiple gene products work together to produce
physical and chemical responses to both static and changing cellular needs.
Sources:
The research paper
The message you tried to print is
protected with Information Rights Management. The sender didn't give you the
rights necessary to print the message.
