THE HUMAN GENOME AND GENETIC DISEASE WEBQUEST

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

http://www.ncbi.nlm.nih.gov/

http://www.ncbi.nlm.nih.gov/

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/

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.