THE
HUMAN GENOME AND GENETIC DISEASE
In
2001, the Human Genome Project completed the sequencing of the entire human
genome. A byproduct of this effort was the identification and mapping of more
than 1,000 human disease genes. The large amounts of data generated by the
Human Genome Project have been organized and made available to scientists and
the general public via several databases. Online Mendelian Inheritance in Man
(OMIM) is one example. OMIM is a catalog of human genes and genetic disorders
developed for the World Wide Web by the National Center for Biotechnology
Information (NCBI). The database contains information about the research
history of the disease gene, inheritance patterns, a clinical synopsis of the
disorder, and information about the molecular nature of the mutation or defect
that leads to the disorder.
Activity
In this
activity you will access the resources provided by the National Center for
Biotechnology Information and research the details of a genetic disease using
OMIM.
Part 1
Use
your browser to go to
Under
the section "Genetics and Medicine" choose "Genes and
Disease."
Choose
the section near the bottom titled Chromosome Map and read the introduction to
chromosome mapping.
*What
are the three main parts of a chromosome, as viewed under a microscope?
a.Three main
parts of a chromosome when viewed under a microscope are two special chromosomes, X and Y, that determine our sex, special units of chromosomal DNA, and the center of each
chromosome, centromere.
It will
be handy to know these as you are looking at maps of chromosomes- these will be
part of the “address” for each gene!
Select
the X chromosome from the list of chromosomes on the right side of the page and
read the summary of the genes found on the X chromosome.
*List
at least four human diseases that have been mapped to the X chromosome.
a.Hemophilia
b.Alport Syndrome
c.Menkes Syndrome
d.Fragile X
Syndrome
Click
on the Map Viewer link at the very bottom of the page (Featured: Mapviewer)or
click here:http://www.ncbi.nlm.nih.gov/mapview/
Notice
that this database has information about the DNA and proteins for many species
(including platypus!).
Choose
the latest build for human (homo sapiens) chromosomes.
Select
the X chromosome.
At this
point you will be looking at the most current map of the known DNA sequences on
the human X chromosome! And yes, its complicated : )
You can
browse through the map of the X chromosome if you wish, zooming in and out. You
may find the “You are here:” diagram on the left side of the page to be handy
(or not).
Perhaps
an easier way to experience the map of the X chromosome is to do a search for
one of the disease genes that you discovered earlier. Do that now using the
search box above the chromosome map.
Once
you get the results, click on the Map Element that looks most promising to you.
This link will take you to a more detailed map of the X chromosome showing
where the disease gene is located.
Click
on one of the reference numbers for that gene to see if you can get some useful
information about it (and there will be a lot of scientific nonsense, so keep
digging or find a summary!)
*Read
the summary section for that gene to find out what functions, processes, and
components it is thought to be involved in (what’s it do?).
Part 2
Hemophilia
A
a.Function: a
deficiency of the blood clotting protein known as Factor VIII that results in
abnormal bleeding.
b.Process: Mutation
of theHEMA gene on the X
chromosome causes Hemophilia A.
c. Components: X-linked disorders such as Hemophilia A are far more common in
males. The HEMA gene codes
for Factor VIII, which is synthesized mainly in the liver, and is one of many
factors involved in blood coagulation; its loss alone is enough to cause
Hemophilia A even if all the other coagulation factors are still present.
Return
to the Genes and Disease table of contents where you began this exercise (http://www.ncbi.nlm.nih.gov/books/NBK22183/).
Choose
a topic from the menu at the left (Cancer, Immune System, Metabolism, and so
on).
Read
the introduction to the disease type you have chosen, then choose a specific
disease to study.
Read
the information about the disease you picked and use it to answer the following
questions:
*What
disease did you choose and what gene is/genes are associated with this disease?
a.The disease
that I chose is called Rett Syndrome. The genes that are associated with RTT
are mutations in the gene MeCP2
*On
what chromosome are these genes/is this gene located?
a.Found on the X
chromosome.
Use the
link at the side of the disease page to go to the OMIM entry for the disease
you chose.
*Read
the text section and the clinical synopsis in the OMIM entry and answer the
following questions:
- When was the disease first reported in the
scientific literature?
·
Rett
, a Viennese pediatrician, first described Rett syndrome after observing 2
girls who exhibited the same unusual behavior who happened to be seated next to
each other in the waiting room. (Around 1966-1977)
- What are some of the clinical symptoms of this disease?
· a period of clear developmental regression followed by limited
recovery or stabilization. Other main criteria include loss of purposeful hand
skills, loss of spoken language, gait abnormalities, and stereotypic hand
movements. Although deceleration of head growth is a supportive feature, it is
no longer necessary for diagnosis. Exclusion criteria include other primary
causes of neurologic dysfunction and abnormal psychomotor development in the
first 6 months of life.
- What lab findings (gene function or
biochemical data) are associated with the disease?
- an MECP2 mutation, that resulted in
decreased, but not absent MECP2 function.
- What type of inheritance governs this disease?
· family recurrences of Rett syndrome comprise only approximately 1%
of the total reported cases; the vast majority of cases are sporadic.
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